seroquel xr for borderline personality disorder continuing review, university of minnesota irb

8/9/2019 Seroquel XR for Borderline Personality Disorder Continuing Review, University of Minnesota IRB

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University of Minnesota

-Continuing-Rev-iew-of-I RB-̂Pending-

:Medca,LResearch ..—=^

Review Period:01/10/2008-01/09/2009

Rev; 03/01/2005

- St udy Num0- - . -

Principal I nvestigator: Sellmann C SchulzTitle(s): Seroquel XR for the Management of Borderline Personality Disorder:

A Randomized Double-Blind Comparison with Placebo

Study StatusA ctive (E nrolling Subjects)

Funding Source(s)Funding Source:Funding Type:

Funding Source: AstraZenecaF unding Type: OT H E R

AGENDA.i M̂ J MSL

PersonnelSchulz, Selimann (P. I .)

Crow, Scott (Co-lnvestigator)

Milev, Peter (Co-lnvestigator)

Miller, Michael (Co-lnvestigator)

Moen, Richelle (Co-lnvestigator)

Romine, Ann (Correspondent)

I nvestigational Drug(s)IND N umber: 45,456IND.Holder: AstraZeneca (Sponsor)I DS N umber: 3462

Study EnrollmentNumber of Subjects Approved for study:

50

Number of subjects enrolled this review period:

Ma eFema eUnknown TotalT T 0 ~T2~

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Number of subjects enrolled to date:-Male- —- —-Female- ~~~" "Unkn'own •

_̂1=1——— -0 —̂2=̂I s this a multi-center study?

YesTotal national accrual to date; 2

Unanticipated Problem ReportingSince the most recent IRB continuing review approval, have any participants withdrawn from theresearch?

No

Since the most recent IRB continuing review approval, have any participants complained about theresearch?

No

Have any serious and unexpected adverse events been reported to the I RB?

No

Study SuimmarySummarize preliminary information about any results and/or trends:

I n beginning phases of enrollment with 2 subjects enrolled.

Have there been any changes in protocol approved by the IRB since last continuing review?

No

Since the most recent IRB continuing review approval, have there been any progress reports on theresearch?

N o

Since the most recent I RB continuing review approval, have there been any multi-c.enter trial reports?

N o

Since the most recent I RB continuing review approval, have there been any other informationrelevant to this research discovered, especially information about the risks and benefits associatedwith the research?

The University of Minnesota is an equal opportunity educator & amployer. Page 2©2004 by the Regents of the University of Minnesota.

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No

Since the most recent I RB continuing review approval, have subjects experienced any benefits?

Yes

2 acti.ve subjects report receiving benefit frpm.stydy.participatjon {hys_far,

External FindingsIs there anything in the relevant recent l iterature that the IRB should know about concerning thisresearch?

No

Consent/Assent FormsHave there been any changes to the consent and/or assent form(s) since the last I RB approval?

No

Have. translated consent short forms been used in conjunction with an interpreter to obtain consentfor this study?

N o

Other Comments

Study start has been slgnigicantly delayed by contract hold-ups.

The University of Minnesota is an equal opportunity educator & employer. Page 3©2004 by the Regents of the UnlvsrsityofMlnnssota.

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rP-Tr"—-—S-cbulz,:Sellman=̂—•̂""—=—O.TiiveFsitŷf-M:imeso'̂

HSC# 0709M16844 Research Subject's Protections ProgramsRev ewer: • I nst i tuti ona Rev ewBoard

-Meeting-Date:- -——• ——- -- "—-———- - —- —- —• —•-—

Ful l Committee Review—Continuing Review of Approved ResearchI f you choose to submit this form eleytt-onically, please send to u-b(%umn.edu.

"/in I RS shall conduct 'continuing review of research covered by thi s policy ut inte.n'als appropri ate to the

degree ofmk, but not less than once per year, andfsha/i have the aulhorU y to ohaen'e or have a third partyohseri'e the consent process and the research."21CFRS6.109 and 45CFR46.109

"Continuing, r eview ofresuurch must be sii bslcuiiive and meamngfii l."OffRP Guidance on Continumg Review 1-15-07

Study status: [X] E nrolling subjectsFollowing subjects

D On holdClosed to enrollment

Study Enroll ment: N ote any issues. I s enroll ment as expected, has PI overenroHed, isthere a lack of subjects or are they nearing approved totals? Is the PI requesting moresubjects OR should PI request more subjects?

2 of 50

Funding; Any changes in the last year? Q Yes • D NoFederal l yfunded?. DYes DNo

Study personnel; Any personnel changes in the last year? Q Yes Q N oAre personnel lists in agreement with recent Con Ren form and consent forms?

D Yes D NoList discrepancies: Nathalie Vizueta, MA. listed on consent - not listed on con rev form

Conflict of I nterest: Have there been any change in COI in the last year?

Yes QNo

I nvestigation al Drugs or Devices: Have there been any changes or additions in thel as yea ? QYes QNo

UPTRT SOS (unanticipated problems or serious adverse events): Since the most recentI RB continuing review approval have there been any UPIRTSOS to report?

D Yes D No

L ist issues or concerns: none given

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Study Summary: I s the summary descriptive enough to assess ongoing ri sk andbenefit -in relation to the length and complexity of the study?

l -.Y-es- ""QNo

C omments: study just star ted enroll ment - two patients receiving medication have reported benefit

E xternal Findings (such as interim analysis or DSM B reports, etc.): Tins reportshould reflect how long the study as been open.

Yes QNoComments: none to report

Consent and Assent Forms: Are forms current for 1KB practice and/or standards?D Yes D No

I f the risks and/or benefits are not described accurately the committee should discuss andmake a determination. (Please edit forms and hand in edited, forms to IRB staff.)

Comments:

I nclusion of Chil dren in Research:

I f children are included in this research confirm that they should still be included m thisr esear ch. QYes DNo[X] NA(According to Subpart D and tlie requirements for pennisyion by parents or guardians andfor assent by children, 45CFE46.408, see yellow sheets).

I f children are included this inclusion must meet one of the following criteria forrisk/beuefit assessment according to federal regulation (21CFR56 and 45CFR46 Subpart

D, see yellow sheets),

[_] (404) Minimal riskI j (405) Greater Ami minimal risk; but holds prospect of direct benefits to subjects.

(406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely toyield generalizable knowledge about the subject's disorder or condition.

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Criteria for I KB _AK Prova]:

Confirm that the criteria for I RB approval are still met.(21CFR56.111 and45CJ ?R46.ni)

I I Risks to subjects arc minimi/.ed

[_] Risks to subjects are reasonable in relation to anticipated benefit, I f any, to subjects,and the importance of the knowledge that may be expected to result

Q Selection of subjects is equitableI I I nformed consent will be sought from each prospective subject or the subject's legally

authorized representative, in accordance with 21CFR50 and/or 454CFR46.116

Q I nformed consent will be appropriately documented, in accordance with 21CFR50.27and/or45CTR46.U7

Where appropriate, research pl ans make adequate provisions for monitoring the datacollected to ensure the safety of subjects, QYes | [ NA

Where appropriate, there arc adequate provisions to protect the privacy of subjects and tomantanconfi denti ai tyof da ta. • QYes DNA

Where appropriate, vzilncrable populations have adequate protection; risk and benefitanalysis confirms their inclusion in the research. [_J Yes Q NA

General questions:

**m' questions 1-4 are YE S please address and document in the comments anddiscussion section.

1. Does the ongoing continuing review information indicate any alteration in the risk andbenefit balance or ratio from previous reviews? Q Yes Q No

2. Does the consent or assent form(s) require revision or updating? Q Yes ' | | No

3. Does the ongoing continuing review information prompt notification ofstudy subjectsa r eadyenr o l ed?QYes QNo

4. Should the committee request or seek verification of information from other sources,

such as DSMB, fonder, sponsor, or literature search? [_] Yes D No

I f question 5 is NO please address and document in the con-iments and discussion section.

5. If vulnerable populations previously were subjects should they continue to be includedin this research? Q Yes • Q No DNA

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-I .s-lh v-i'-vy-i tiW—iutciL v.d 1-s ti l l-ap.p r-o.pE ii i.te-toi—this ŝ.tu.dy-i

For continuing review approval federal regulations state that studies need to be reviewedno-iess-that yearly-but the-committcc may-set continuing-feview-at-a-morefi'equent-

interval.

Check the review interval appropriate for tllis study:Annually

D E very 6 monthsQ Quarterly

Other interval (state specific renewal interval and provide justification)

Committee Determination:Cannot make "suggestions " due to automatic email, suggestions must be listed as

stipulations

Q Approved as Submitted: no change required in ongoing approvalApproved with Stipulations: as noted

Response to original reviewerQ Response can be reviewed by expedited review (by senior staff)

Approval Deferred: additional information required. This is a serious decision asdeferral halls all research processes. Committee should 'consider subject status and

funding issues. Response will go back to the continuing review committee for review

Common stipulations:

Update Contacts and Questions section information on the consent forms;i.e. "University of Minnesota Medical Center Fairview"

D Add HI PAA reference on the consent form.

D Add the human subject code numbcr/page numbers/version date to all pages of theconsent forms,

The 1RB should observe the consent process or the research,

n Reapply as required every 5 years,

I have completed a substantive and meamngfyl review based ou.the informationmade available at thi s time.

Print name of reviewer: KG J ohnson

Signed name of reviewer;

Date: 12/17/2008

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-D o Gum ent-items-fo îeommttee-iidis cus sioti b̂ elo w:-

Document "comments, changes, and stipulations" below:(write out stipulations clearly)

N athalie V izueta, M A. l isted on consent and not listed on con rev form

C orrect address for out-of study conta ct In formati on - remove room number, and correct streetnumber

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Committee Meeting MinutesDecember 17, 2008

Agenda I tem:iContinuing Review-Medical

Agenda I tem: None

Agenda I tem: None

PI : Schulz, Sell mann Reviewer: J ohnsotf

Reviewer; Belew

Protocol Title arid HSC#"Seroquel^̂^̂fôARandomiZed ôubl êUudG m̂paruoni?̂ Placebô

I tem Description:N one;.l"?;

(Discussion of Controverted Issues Summary:

There were no controverted issues.

iRevisiftnSt


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12/19/2008

. . . Se l mnnCSchuz_ . •, \ . . ^ : f M^

Psychat r yDepar t ment \ \ ^^• F282AW- B• . ^

2450 Ri versideMinneapolis, MN 55454

RE ; "Seroquel XR for the Management of Borderl ine Personality Disorder: A RandomizedDouble-Blind Comparison with Placebo"IRB Code Number: 0709M16844

Dear Dr. Schulz,

.At the meeting on December 17, 2008, the I RB; Human Subjects Committee reviewed thereferenced study. The following stipulations must be resolved, mid written approval should bereceived, before renewed approval is confirmed,

The following changes to the consent form are stipulated;

• Correct the following standard language in the Contacts and Questions section of the0 consent form: I f you have any questions or concerns regarding the study and would like to

talk to someone other than the researcher(s), you are encouraged to contact the FairviewResearch H elpline at telephone number 612-672-7692 or toll free at 866-508-6961, Youmay also contact this office in writing or in person at University of Minnesota Medical

Center, Fairview Riverside Campus, 2200 Riverside Avenue, Minneapolis, MN 55454.

^. •Please provide a copy of the revised consent form for review.

We cannot confirm the renewal of the referenced study until these conditions are met, I f your

response is not received within ninety days, the study wil l be filed inactive.

Please send your response to RSPP (Mayo Mail Code 820; D-528 Mayo Memorial Building; 420Delaware St, SE; Mmncapolis, MN 55455) The entire application does not need to be resubmitted;your, response should address the sections requiring change. The signature of the Principal

Investigator is the only signature required with the response. Only one copy of the response isnecessary,

I f you have any questions, please contact the IRB office at 612-626-5654.

Sincerely,

Andrew AlienResearch Compliance SupervisorAA/mqCC: Scott Crow, Peter Milev, Michael Mil ler, Richelle Mocn, Ann Romine, Nathalie Vizueta

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Date: 01/06/2009To: S. Charles, Schulz ([email protected])

From: [email protected]

Subject: #STUDYN BR#- PI #PI L ASTNAME#- IRB - APVD Continuing ReviewMessage: TO : [email protected], [email protected], [email protected], [email protected],

[email protected], mjmi [email protected], [email protected],

The IRB: Human Subjects Committee renewed its approval of the referenced stidy

listed below:

Study N umber: 0709M 16844Principal I nvestigator: Sellmann SchulzE xpira tion D ate: 12/16/2009Approval Date: 12/17/2008Title(s):Seroquel XR for the Management of Borderline Personality Disorder: A RandomizedDouble-Blind Comparison with Pl acebo

This e-mail confirmation is your official University of Minnesota RSPP notification ofcontinuing review approval. You will not receive a hard copy or letter.

This secure electronic notification between password protected authentications hasbeen deemed by the University of Minnesota to constitute a legal signature.

You may go to the View Completed section of http://eresearch.umn.edu/ to view or

print your continuing review submission.

For grant certification purposes you will need this date and the Assurance ofCompliance number, which is FWA00000312 (Fairview Health Systems ResearchFWA00000325, Gillette Childrens Specialty Healthcare FWA00004003). Approvalwill expire one year fr om that date. You will receive a report form two months before

the expiration date.

In the event that you submitted a consent document with the continuing review form, ithas also been reviewed and approved. I f you provided a summary of subjects'

experience to include non-UPBRT SO events, these are hereby acknowledged.

As Principal I nvestigator of this project, you are required by federal regulations toinform the IRB of any proposed changes in your research that wil l affect human

subjects. Changes should not be initiated until written IRB approval is received.Unanticipated problems and adverse events should be reported to the IRB as theyoccur. Research projects are subject to continuing review.

I f you have any questions, please call the IRB office at (612) 626-5654. The IRBwishes you continuing success with your research.


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University of MinneAQta.

GontinuingReview-of-lRB-- Pending

Medical Research

KUV IBW Pertofl'10/29/2008-12/16/2009

Rev: 03/01/2005

Study N umber: 0709M 16844Principal I nvestigator: Sellmann C SchulzTitle(s): Seroquel XR for the Management of Borderline Personality Disorder:


Study StatusActive (Enroll ing Subjects)

Funding Source(s)Funding Source: AstraZenecaFunding Type: OTHER

G E N D,_£̂̂0̂

PersonneSSchulz, Sellmann (P. I .)


Milev, Peter (Co-lnvestigator)

M ill er, M ichael (C o-lnvestigator)

Moen, Richelle (Co-I nvestigator)


Thompson, Marian (Co-lnvestigator)

Study EnrollmentNumber of Subjects Approved for study;

50


MaeFemaeUnknownTota

]1 K -ENumber of subjects enrolled to date:

Ma eFema eUnknown Total

-n10^

I s this a multi-center study?

Yes

The Uni versity of Minnesota Is an equal opportunity educator & employer,©2004 by the Regents of the University of Minnesota.

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Total national accrual to date: 14

Unanticipated Problem ReportingSince the.most recent I RB conlinuing review approval, have any participants withdrawn from theresearch?

Yes-

2 subjects have withdrawn due to intolerabil ity of study medication. 1 subject withdrew at visit 10 for reasonsunknown,

Since the most recent I RB continuing review approval, have any participants complained about theresearch?

N o

Have any serious and unanticipated problems been reported to the I RB ?

No

Study SummarySummarize preliminary information about any results and/or trends;

Majori ty of subjects enrolled have completed study or are currently active In study. Many have reported andpresented reduction in symptoms of BPD. Medication intolerabllity reported by at least 2 subjects in the form ofsedation.

Have there been any changes in protocol approved by the I RB since last continuing review?

Yes

We are developing protocol amendment #2 and will submit in paper copy with this form.

Since the most recent I RB continuing review approval, have there been any progress reports on theresearch?

No

Since the most recent I RB continuing review approval, have there been any multi-center tr ial reports?

No

Since the most recent I RB continuing review approval, have there been any other informationrelevant to this research discovered, especially information about the risks and benefits associated

with the research?

No


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Yes

-Many~subJ e'cts-h'aVB-re'po'rted-aTTd presenteclT ecluctlomn symptoms of'BPD7

External F indings

I s there anything in the relevant recent literature that the IRB should know about concerning thisresearch?

No

Consent/Assent FormsHave there been any changes to the consent and/or assent form(s) since the last I RB approval?

Yes

We are submitting a revised consent upl oaded with this form, dated 30 SE P 2009. The revision is on p. 9,highlighted in yell ow, change form Signature of I nvestigator to Signature of Person Obtaining Consent.

Have translated consenl short forms been used in conjunction with an interpreter to obtain consentfor this study?

N o

Other Comments

The Unlvarsity of Minnesota is an equal opportuni ty educator & employer. Page 3© 2004 by tha R egents of (he Uni veralty of M innesota,

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"»

P: SchuzUn vers tyof MnnesotaHSC # 0709M 16844 Human Research Protection ProgramRevewer: Dees Inst i tuti onal RevewBoar d

-Meetmg-Date; 1-ZT6/2009 —

Full Committee Review—Conitmiuiing Review of A pproved Research

•• »••"An I RB shall conduct mntinuing revie\ v of research covered by this policy at intervals appropriate fo the degree ofmk, but not less than once per year, and shal l have the authority to observe or have a third party obsewe theconsent process and the research. " 2 CFR56.J 09 and45C.F R46.109

"Contmnlng review of research must be substantive and meaningfid," OII RP Guidance 1-15-07

Short T itle: To determine the safety and efficacy of Seroquel XR for treatment of BorderlineP ersonality Disorder

Enrollment: ̂ Open Q Closed Q On hold

Treatment: ̂ Continues Q Complete [_| Not a treatment studyFollow-up: [3 Continues d Complete D N o follow-up required

Funding; Q Federal [X] Sponsored Q Foundation Q Departmental

Enrollmient Numbers: Approved: 50 Enrolled: 6 Years active: 2

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others):Have any UPI RT SOs been reported in the last year? Q Yes ̂ N oAre there concerns to be discussed by the Committee? | _| Yes DO No

Study Summary: Q Adequate D DeficientNone - too early Q None - data analysis elsewhere

External Findings: D DSMB letter D Progress report Q Action letter

Consent and Assent F orms: ̂ Submitted Q Missing Q Waived or not applicableHI PAA Forms; 0 Submitted ̂ Missing Q Waived or not applicable

Closed to enrollment - forms are no longer pertinentAre all persons listed on consent form also listed on the 1RB roster? Q Yes Q No

I nclusion of Children in Research;I f children are included in this research confirm that they should still be included,

Yes D No [X] NA - children excludedI f chil dren are included this inclusion must meet one of the following criteria for risk/bcnefitassessment according to federal regulation (21CFR56 and 45CF R46 Subpart D),

(404) M inimal r isk.D.(4P5).< reaterthanmlmmal nsk; buthplds prospect of direct benefits to subjects.Q (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely toyield generalizable knowledge about the subject's disorder or condition,

University ol'Mi nnesotn J RBContinuing Review FormV ersion 10/27/09

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Substantive Changes: If any of the following are evident from the continuing review,describe the changes for Committee discussion,

D Change in risk or benefitQ Change in subject population

Minor changes in consent form

I I Major changes in consent form

D Change in fundingQ Change in conflict of interest

Change in data management

I tems for Committee Discussion:1. Staff-Note that second consent form that appears on the flash drive and displaying IRB Approval; 30Sep 2009 in footer is the most recent version2. Was Appendix A completed and submitted with the original appl,? I t is not in the circulati on copy on thef l ashd ve ' ' ^\ \ ^^^.

2. Consent form-ls there a reason why the standard research related injury wording was previouslyapproved rather the the l anguage for a sponsored study?

Recommended Stipulations:1. Submit copy of current HI P AA form2. Ĉ ooseftH orm7R 151


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•. ^

P; SchuzUn vers tyof MnnesotaHSC# 0709M16844, Human Resea rch P rotect i onProgram

Revewer: Kracn Inst i tui onal RevewJ joard"M eefmifD aie:—T 2/T 6?2009-

Ful l Committee Review—Continumg Review of Approved Research

•••••••"An 1RB shall conduct continumg, review of research covorsdby {his policy at intervals appropriate to the degree ofri nk, hut no less than once. per year, and shall have the.authwily to observe or have a third party ohsei've the

cement process and the research. " 2J CF R56. f Off and 45CF R46.109

••«un • i"Continuing review of research nmst be substantive and meaningful." OI IRP Guidance 1-15-07

Short T itle: Seroquel X R for the management of borderline personality disorder: RC T

Enrollment: [̂Open Q Closed [_] On holdTreatment: [x] Continues Q Complete [_] N ot a treatment studyFollow-up; ̂ Continues D C omplete Q N o follow-up required

Funding; Q Federal Ŝponsored Q Foundation Q Departmental

EmrommentNmmbers: Approved: 50 Enrolled: 6 Years active: 2

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Olhers):Have any UPI RT SOs been reported in the last year? Q Yes [E l NoAre there concerns to be discussed by the Commttee? Q Yes | N̂o

Study Summary: 13 Adequate D DeficientNone - too earl y [_] None - data analysis elsewhere

External Findings; Q DSMB letter Q Progress report Q Action letter

Consent and Assent Forms: [̂ Submitted Q Missing Q Waived or not applicableHIPAA Forms: Q Submitted | E1 Missing Q Waived or not applicable

Q Closed to enrollment - forms are no longer pertinentAre all persons listed on consent form also listed on the IRB roster? [̂Yes D No

I nclusion of Chil dren in Research:I f children are included in this research confirm that they should still be included.

Yes I I No DO NA - children excludedI f children are included this inclusion must meet one of the following criteria for risk/benefit

assessment a ccording to federal r egulati on (21C F R 56 and 45C F R 46 Subpart D).(404) Minimal risk

D (405) Greater than minimal risk; but holds prospect of direct benefits to subjects.(406) Greater than minimal risk; no prospect of direct benefit to subjects, but l ikely to

yield generalizable knowledge about the subject's disorder or condition,

Uni versity of Minnesota IRBContinui ng Review FormV ersion 10/27/09

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Siabstamtive Changes: I f any of the following are evident from the continuing review,describe the changes for Committee discussion.

Q Change m risk or benefit [~}Change in fundingI I Change in subject population D Change in conflict of interestII Minor changes in consent form D Change in data management

I I Major changes in consent form

I tems for Committee Discussion:1, Three subjects have withdrawn-2 did not tolerate drug (sedatlon), one reason unk nown,2. Protocol Amendment 2 being developed, Not along wi th this form,3, M inor change to consent form-sig nature of person obtain ing consent rath er than P i

Recommended Stipulations:1. P rovide HI P AA form

Recommended Suggestions;

Reconn mended Action: Q Approve as SubmittedApprove with Suggestions

c"ck.tosh-ow IS Approve with Stipulations as notedCri teri a for I '" " 'I lr— '•̂—- -r -—^̂——̂-

VA'pP'rovaT | U Response to original reviewerResponse can be reviewed by TRB staff

Q Approval Deferred " additional information required

Continuing Review I nterval: [X] AnnuallyEvery 6 months

I I Quarterly

[_j Other interval;

/ have completed a substantive and meaningful review based on the information made availableat this time.

Print name of reviewer; L idna E , Krach, MD Date: 12/16/2009

Signed name of reviewer:

I f you choose to submit this form electronically, please send to irb(Sl,umn.edu.Forms submitted from a umn.cdu account do not need a hard-copy signature,

Uni versity of Minnesota IRBContinuing Review FormV ersion 10/27/09

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Committee Meeting MinutesDecember 16,2009

Agenda I tem;Continuing Review-Medical

Agenda If eni:; None

Agenda I tem; None

Pt; Schub, Sellmann Kevie'wejft Krach

'Iteyie'wer;:i?(Dees?:

Protocol T itle and MSC?#:''Seî q^ARd̂omizedDoublêuidCompansonmtKP 1̂̂:,̂ Kii?l^̂:®l{-,:l-| ::i

ItemDescri pti on X- . ,1":1;- ^~': :x̂

M revises consent form with a m^

D̂i scussion of Gontrovertea I ssues Summai-y;


| Reyisions,>CI aril âtipiMorStipuI atiQns::̂


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Committee Meeting MinutesDecember 16, 2009

Determinations and J ustifications Requir ed by Regulations and Guidelines:

N one

I RB Decision:

Approve Continuing Review with Stipulations

Additional I nfo: None

L ength of Approval: One Year

VoteYes: 9 No: 0 Abstain: 0 N ot Pr esent:

Members Not Present for Vote Due to Conflict of Interest: None


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12/17/2009

Selhnaim C Schulz

Psychat r yDepar t ment 8393^F282/2A West-B2450 Ri versideMinneapolis, MN 55454

RE : "Seroquel XR for the Management of Borderl ine Personality Disorder: A RandomizedDouble-Blind Comparison with Placebo"IRB Code Number: 07(»9M16844

Dear Dr. Schulz,

At the meeting on December 16,2009, the Institutional Review Board (TRB) reviewed thereferenced study, Tl ie following stipulations must be resolved, and written approval should be

received before renewed approval is confirmed.

• Please submit the most current version of your HI PAA Authorization Form for review.This form is now required at the time of continuing review, The IRB has initiated thisnew requirement to help maintain substantive and meaningful review of all continuingreview submissions.

The following changes to the consent form are stipulated:

• As this study is funded by a corporate sponsor, the following standard 'sponsor-funded'injury compensation language should be used in the consent form:

'In the event that this research activity results hi an injury, treatment wil l be

available, including fi rst aid, emergency treatment, and follow-up care as needed,Care for such injuries will be billed in the ordinary manner, to you or your insurancecompany. The sponsor of the study has some funds available to pay for care forinjuries resulting directly from being in this study. If you think that you have

suffered a research related injury and that you may be eligible for reimbursement ofsomemedca carecost s, l et the st udyph ysi cans kn owr i ght away' j

—I f the research contr act makes an exception for the corporate sponsor not to beliable for research related injury payment, then please provide documentation(pert i nent seci on o f thecont rac) tosupport ths. |

Please provide a copy of the revised consent form for review.

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-P-kase-note—n̂he-Gontwumg-r-eview-for-m̂t-stated̂hat-an-ame'ndment-̂ wouÛ̂

for review. The IRS has yet to receive this. Please submit (he amendment -when it is ready forreview.

The enrollment of new subjects may continue using previously approved consent document(s),We cannot confirm the renewal of the referenced study until these conditions arc met, I f yourresponse is not received within ninety days, the study will be filed inactive,

Please send your response to I-IRPP (M ayo Mail Code 820; D-528 Mayo Memorial Building;420 Delaware St. SE; Minneapolis, MN 55455), The signature of the Principal Investigator is

the only signature required with the response, Only one copy of the response is necessary.


Sincerely,

Movolny, CI Ptrch Compliance Supervisor

)/mq

CC: Scott Crow, Peter Milev, Michael Miller, Richelle Moen, Arm Romine, Marian Thompson

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SC.R-UIẐ-,̂2-

UNI VE RSI TY OF MI NNE SOTA °̂Ml b 4̂ [̂ ̂1%%̂^ b^uu— ~11

Twin Cities Campus Ambututory Research Center Riverside Prdfessiwol Swid'mg~6(16'2'4h~Ave>we Smth —~~

Department of Psychiatn-December 30 2009 MS/ ' . s - cAoo/ ' ' SmmW2

l wmc" >ww"Mi mMmi -i , AW55454

Chi st i na D obr ovo ny osw 6262748W

Institutional'Review BoardUniversity of MinnesotaMayo Mail Code 820D528 Mayo Memorial Building KLl'U J AN 0 6 2010420 Delaware Street S.E .Minneapolis, Minnesota 55455

RE : "Seroquet XR for the management of Borderl ine Personality Disorder (B PD)"H SC #0709IV 116844

Dear Christina:

Thank you for your Continuing Review of the referenced study. We are responding to

I RB stipulations as stated in your letter dated 17 DE C 2009, as well as submitti ngProtocoi Amendment #2 dated 30 DE C 2009.

Stipulations:1. E nclosed is the current approved version HI PAA form, version date 24 FE B 2009

& I RB approved on 19 J UN 2009.2. T he research-related injury language has been revised on p. 8 of the revised

consent form dated 30 DE C 2009.3, In addition, we have changed the signature line on p, 9 of the revised consent

form to read "Signature of Person Obtaining Consent" rather than "Signature ofI nvestigator."

Protocol Amendment #2, version date 30 DE C 2009

The amendment i tems are listed & notated in the Protocol Amendment Summarydocument dated 30 DE C 2009, The amended protocol includes changes highlighted inyellow. Please note the green highlights were from protocol Am #1, I RB approved on 02J UN 2008..

We have enclosed the following documents for your review:1) Protocol Am #2 version date 30 DE C 20092) Protocol Am-#2 Summary 30 DE C 20093) Revised consent form version date 30 DE C 20094}Current approved version HI PA A form, version date 24 FE B 2009 & I RB

approved on 19 J UN 2009

Thank you and please contact Ann Romine, study coordinator, with any questions at

612.627-4843,

Sincerely,

S.̂ MM l̂ îS. Charles Schulz, MDPrincipal investigator

Driven to Discover5

Page £


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U N I V E R S I T Y O F M I N N E S OTA

Change I n Protocol RequestRCT .AN 13 2010

ŝHu-i/2- -0-jôt̂ y-f̂

z/,g/.,,AGE ME' / / Oni ^^ac^^ ^

-I nstr-uc.tJ oos;-Usa this form when submitting change requests on 1KB protocols.

t. Submit this form to the Human Research Protection Pr ogram:

U .S, Mail Address:Human Research Pr otection Program

M M C 820420 Delaware St. SEMi nneapoli s, M N 55455-0392

I RB Protocol I nformation

Campus Mail;Human Research Pr otection ProgramM M C 820Minneapoli s Campus

Delivor to:D-528 Mayo Memorial Building

. Minneapoli s Campus8-4:30, M-F

I RBSludy Number:

Currenl Principal I nvestigator:

l-'rbnary Title:

Submission Date

0709M 16844S. Charles SchulzMD, Dept Head30 DEC 2009

I ndn'.ale the type of change/addition and attach all applicable documents:I ZIProlocol Amendment; Version ,̂ Dated 30 UE C 2009[_J Revised J nvcstigator Brochure; Ver.siun , Unted

QR.ccruitinentChanges/Advertisemenl.s

DN otice of C losure to AccrualQChangei's') tn Study ProceduresdOl'her:

1. l r̂i ct'ly summari ze (lie uhungc(s). Kor prol.oco amendments, do not say "See summary of changes provided will)

amendment," Rather, summarize t)u> nature of the significant revisions.

Cl ari fication of procedures including visit windows, study mediuati un compliance, frequency of 2 side effectassessments, earl y discontinuatjon, ynd siratif'ication by genduT.

2, Describe the rationale lor the cttange(s);

To clari fy procedures Co ensure consistency of study methods across a)) 3study si tes.

3. In your opini on as principal investigator, how will tl iese changes affect the ovt'rall ri sk to subjects in this sfii dy?

These changes will not increase ri sk to subjects.

4. Do the changes to the study prnmpl changes to the consent form(s)?


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Continuing Review of I RB - PendingMedical Research

Review Period:09/25/2009-02/17/2011

Rev; 03/01/200.5

Study N umber: 0709I V I 16844Principal I nvestigator: Sellmann C SchulzTitle(s): Seroquel XR for the Management of Borderline Personality Disorder:


Study StatusActive (Enrolli ng Subjects)

Funding Source(s)F unding SourGe: ASTRAZEN E CA IN TLF unding Type;

PersonnelSchulz, Sellmann (P. I .)


Cullen, Kathryn (Co-'lnvestigator)

Man, Georges-J akofci (Staff/L ab)

H eller, M onik a (Staff/L ab)

H ouri, A laa (Staff/L ab)

Miller, Michael (Co-lnv̂stjgator)


Rom ine, Ann (Correspondent)

Vuchetich, J ohn (Co-lnvestigator)

Study Enrollment

N umber of Subjects A pproved for study:50

Number of subjects enrolled this review' period:

Ma eFema eUnknown Total

[I 4̂ J £ J S [Numtser of subjects enrolled to date:

The University of Minnesota is an equal opportuni ty educator & employer.©2004 by the Regents of the University of Mtnnesota.

P age 1


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Ma e Feme Unknown J o ^ E18114| 0f 22}|


Yes


Unanticipated Problem ReportingSince the most recent I RB continuing review approval, have any partJ Gipants withdrawn from theresearch?

Yes

8 early withdrawals and 1 lost to follow-up, 4 early withdrawals were due to adverse events, pri marily sedaitlon. 4due to subject personal circumstances.

Since the most recent I RB continuing review approval, have any partioipants complained about theresearch?

No

Have any serious and unantiGipated problems been reported to the IRB?

N o

Study SummarySummarize preliminary information about any results and/or trends:

At our site 22 subjects have been enrolled and have taken at least 1 dose, of study medication. 13 subects havecompleted all 11 visits of the study. 9 subjects have not completed the study. The majority of subjects whocompleted study to date show a decrease in symptoms from baseline as measured by the assessment scalescores. 2 other sites are parti cipating jn this trial. E ach site has an enrollmentgoalof33subJ Betstoobtain a totalof99 subjects enrolled. Enrollment numbers to date are as follows; University of Iowa: 27 subjects McLean Hospital,H an/ar d U niversity: 3 subjects E nrollment goals ma y:need to be adjusted per sit e as w e get closer to our enrollmenttotal.


Yes

Achartge in protocol, Amendment #3, dated J uly 20,2010, was approved perlRB letterdatec) Novembers, 2010.T his amendment adds an optional brain imaging (fM R t) addendum to the main study. T he Gonsentform and Br ainImaging Addendum dated October 20,2010 was also approved. To date no subjects have been enoll edthe brainimaging study,


No

The University of Minnesota is an equal opportunity educator & employer. Page 2©2004 by the Regents of the University of Minnesota.


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Since the most recent I RB continuing review approval, have there be@n any multi-center trial reports?

No

Since the most nScent 1RB continuing review approval, have there been any other informationrelevant to this research discovered, especially information about the risks and benefits associatedwith the research?

N o


Yes

The majority of subjecte who completed study to date show a decrease in symptoms from baseline as measured bythe assessment scale scores.

External Findings

I s there anything in the relevant recent literature that the IRB should know about concerning thisresearch?

N o

Consent/Assent FormsHave there been any changes to the consent and/or assent form (s) since the last I RB approval?

N o

Have translated consent short forms been used in conjunGtjon'with an interpreter to obtain .consentfor th is study?

N o

Other Comments

The'University of Minnesota is an equal opportunity educator &'employer- Pages©2004 by the Regents of the University of Minnesota.


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Ĉ 50

UNI VERSITY OF MINNESOTA ̂ ^

TwnCti es Ca mpus Depi rtmen of PsychatryF2S22AWst

Memo1450 Riverside AvenueM inneapolis, MN 55454

Office: 612-273-9800

To: S. Charles Schulz, M.D.

From:Scott Crow, M.D.

CC: Kathy Mischke and Kyle Rudser, Ph.D.

Date: April 7, 2010

Re: Seroquel XR BPD Study and Safety Meeting

We met for safety monitoring on March 3, 2010 and interviewed progress to date.The following study issues were reviewed and discussed;

1. There is not sufficient information available on the Harvard site; they haveincomplete information on only one patient and it i s unclear w hether they arerecrui ting or not,

2. No screen failures have been reported. Is this correct? I f there are screenfailures that is not problematic, but it would help in evaluating the rate ofrecruitment.

3. Retention appears to be really excellent. However, clari fication is warrantedin regard to discontinuation of drug and discontinuation of study (i.e,, fromevaluation). I n order to allow for an intent to treat analysis at the end of the

study, patients should be continued to be evaluated to the degree they allowin the event i t is decided to discontinue treatment regimen.

4. There appear to be preexisting symptoms at study entry that are beingcaptured as AE 's, T hese should not be included as adverse events unlessthey increase in severity or frequency.

5. I f possible, severi ty ratings for the AE 's experienced by the Harvard siteenrollees should be provided.

6. I f subjects do not return pil l bottles for count i t appears that that should belisted as a protocol deviation.

L ast, it w as noted that r ecrui tment from across the sites is lagging behind that i niti allyproposed with current enrollment at less than half of what it is expected to be. I fenrollment stays at the current rate, the study is expected to finish in 5 years ratherthan the planned 2 years.

Driven to Discover5


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Seroquel XR BP D StudyData and Safety M onitoring M eeting 8/26/09

Attendance: Scott Crow, M.D,, Safety Officer

K athy M lschke, C linical Tr ial M onitorKyle Rudser, Biostatistician

Data regarding study recruitment, progress, and protocol adherence (all with blinded treatmentassignment) were reviewed, for the first 10 patients enrolled in :the study. Several issues forfurther clar ificatton/reiterati on were identified:

1, There should b6 clarification ,in the protocol as to whether 50 mg dose is given for thefirst two days or the entire first week.

2. I f an individual is discontinued from the study or withdraws from the study, there is someambiguity in the protocol as to what happens for follow-up. A 14 day follow-up isconducted for subjects who complete a regular end of study termination visit and this

should be the same for early termination/discontinuation subjects if possible, includingmonitoring for adverse events.

3. Al l adverse events, serious or not, and expected or not should be reported.

4. There has been some delay in entering of CRF data into the database. The delayappears to be gradually diminishing over the period of patient follow-up visits but there isan overall concern. While there is no specification of expected time to data entry, withintwo weeks of "visit 10" would seem appropriate for effective safety monitoring. Adverseevents, however, are stil l to be reported within timelines specifi ed in the protocol.

5. Clarification is needed regarding study rules for visitwindows and classification ofmissed visit/scheduling of subsequent visits.

6, Protocol deviations are not being reported. These include missed visits, missed doses,missing safety endpoints, and general occurrences that deviate from the protocol.

7, There is concern over the lack of data on identified safety endpojnts, Specifically;prolactin, glucose, cholesterol, triglycerides, and BMI (weight and height), which all needto be assessed at both baseline and end of study for all patients.


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M E M O R A N D U MTO Scott Crow MD

CC: Ann Romne

FROM: Dr. S. Charles Schulz, Head, Department of Psychiatry

RE : Seroquel XR BPD Study - Data and Safety Monitoring Meeting

DATE: October 28, 2009

I am writ ing this memorandum to ini tiate a discussion regarding the Data and Safety M onitoringMeeting of August 2009. Dr. Crow you are the safety officer and I appreciate your having discussedthe meeting with me and look forward to hearing your thoughts about my response to the meeting.

I w il l go through each of the point below:

1. I agree there should be clarification as to how long the 50 mg dose is given. I know that wechanged the original protocol after the feedback ffom the Titration and Taper McLean IRB.Attached is the Dosing amendment,

2. I believe it is a good idea to clarify how subjects are managed if they are discontinued or

withdraw from the study. I am not sure it is clear to the Data and Safety MonitoringCommittee that the design of the two week follow up is to be able to transfer people from thestudy to the next phase of their care. Also, people with borderline personality disorder havedifficulties with abandonment and we have always designed our studies to not have the lastrating period be the person's last appointment with us. Therefore, the idea of clarifying tha-tpeople who are withdrawing from the program or are discontinued should have the follow upis a good idea. We wil l request an amendment to clarify the follow-up for those subjects

(P.21).3. The idea of reporting all adverse effects events is of course appropriate. I need more specific

information about how our sites have been doing on this issue and suggestions for how tocomply with this statement.

4. I can understand concern regarding entering data from the CRF into the database. I am not

sure whether this is related to the suspension of entering subjects or some other reason. Ihave discussed with Ann having a teleconference of all sites so we can address this issue.

5. I can understand that it is important to clarify the "windows" and "classification of .missed

visit." We have designed a definition statement and wil l submit as an amendment.6, Regarding theissue of protocol "deviation" I would like Dr. Crow's opinion of protocol

deviation and then work to make sure that they are appropriately recorded.


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7. I have a question regarding the statement of lack of data on identified safely end-points. Ihave seen all of the laboratory studies at each point and am not qui te sure what the'DSMB isrequesting. In the meantime I wil l review laboratory data to examine for any missing values.

I look forward to discussing thi s with you both sooa so that I can make any needed changes to theprotocol.


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P: SchuzUn vers tyof Mnn esotaHSG# 0709M16844 Human Research Protection ProgramRevewer: Ognjanovc I nst i tui ona RevewBoar d

M eeting D ate: 01/26/2011

Ful l Committee Review—Continuing Review of Approved Research

I"An 1KB shall conduct cwtini iing revbw of research covered by this policy at intervals appropriate to the degree ofri sk, but not less than once per year, and shall have the authori ty to obsen'e of have a third party obsen'e theconsent process aii dlhe r esearch." 21CFR56.109 and45CF R46.109

"Continuing review of research must be substantive and meaningful." OHRP Guidaiice 1-15-0.7

Short T itle: Seroquel XR for the M anagement of Borderline Personality Disorder:A Randomized Double-Blind C omparison with P lacebo

Enrollment: ̂Open D Closed D On holdTreatment: [X] Continues Q Complete [_] 'Not a treatment study

Follow-up: Ĉontinues D Complete D N o follow-up required

Funding: D Federal [X] Industry Sponsored Q FoundationDepar t ment a QNone

Enrollment Numbers: Approved: 50 Enrolled: 22 Years active: 5

UPIRTSOs (Unanticipated Problem InvQlvlag Risk to Subjects or Others):Have any UPIRTSOs been reported m the last year? Q Yes ̂ No

Are there concerns to be discussed by the Committee? Q Yes 1 ̂N o

Study Summary: ̂Adequate D Deficient[_] None - too earl y Q None - data analysis elsewhere

External Findings: ̂ DSMB letter D Progress report D Action letter

Consent and Assent F orms; ̂ Submitted D Missing d' Waived or not applicable

HI PAA Form$; D Submitted d Missing D Waived or not applicableQ Closed to enrollment - forms are no longer pertinent

Are all persons listed on consent form also listed in the I RB records? Q Yes ̂ No

I nclusion of Children in Research:If children are included in this research confirm that they should still be included,

D Yes D No ̂ NA - children excludedI f children are included, is there new information which affects the regulatory classification

(45CFR46 Subpart D) indicate the change,

(404) M inimal riskD (405) Gr eater t han mini mal r isk ; but holds pfospeG t of direct benefits I Q subjects.Q (406) G reater than mi nimal ri sk; no prospect of direct benefit to subjects, but li k ely toyield generalizable knowledge about the subjects disorder or condition.

University ofMimiesotaIRBContinuing ReviewFonnVersion October 2010


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Substantive Changes: I f any of the following are evident from the continuing review report,describe the changes for Committee discussion,

Change hi risk or benefit

D Change in subject populationMinor changes in consent form

D Major changes in consent form

Q Change in fundingQ Change in conflict of interest

Change in data management

I tems for Committee Discussion:- Scott C row w as a member of DSM B and a co-investigator?

Dr. Crow is reviewing subjects' adverse events

for all three sites to monitor subjects' safety,this lias been approved by the IRB previously and

is included in 4.4 of protocol.-Dr Shul tz i s a member of the Scienti fic Advisory Board of Astr a Zeneca (the sponsor), where they discussother uses of the medication Seroquel, and Dr Shultz is the Pl of this study that is trying to investigate ifSeroquel can be used for other pur poses than thus far approved. C onflict of interest?

Recommended Stipulations:- Scott Crow is mentioned in the consent, but is not an investigator on the IRB application,

Recommended Suggestions:

Dr. Crow is a cuiTent Co-PI on the study. He was added after

original review oftlie project,

Recommended Action;

gguuumilllllliilBl.HIII

Q Approve as Submitteda Approve with Suggestions

Approve with Stipulations as notedResponse to original reviewerResponse can be reviewed by IRB staff

a Approval Deferred - additional information required

Continuing Review Interval: [X] Annually

[_] Every 6 monthsQuarterly

Q Other interval:

I have completed a substantive and meaningful review based on the mformation made availableat this lime.

Print name of reviewer; Simona Ognjanovic Date; 1/26/2011


I f you choose to submit this form electronically, please send to irb(%umn.edu.Forms submitted from a utnn.edu account do not need a hard-copy signature.

University of Mi nnesota IRBContinuing ReviewFonnVersion October 2010


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Committee IVI eeting Minutes

J anuary 26, 2011

Agendaltem:1Continuing Review-MedicaI

Agenda I tem:; None

Agenda I tem: None

pl: Schulz, Sellmann ReViêyer; Pgnjanoxic

Reviewer: N oMe

Protocol Title and HSC :̂''Seroquel XR for ^ARandomizedDoublêlmdConip î ŝpni ŴPI aĉ

I tem Description:-N6ne . l '-l ,\ :-^%

| Di stussioalof:e(mtroYerted:Issues, Summary:̂ , f̂,;:';;,; :;V;-; ,;̂

The I RB committee notes that the Pl 's conflict of interest management pl an has been reviewed previously by the I RBCommittee. T he committee acknowledges current, I RB approved language in the consent form that r eferences thePl 's role on the Scientifi c Advisory B oard.The committee also notes that Dr. Scott C row is a co-investigator and he is monitoring adverse events from all threeparti cipating si tes. This does not create a confli ct of interest as r esearchers are required to monitor adverse events.

iRevisions, Clarifications or jStipulatidns:N one

Change ii i Risk/Benefit Balance;N one

Committee Must Address:

E l 21C F R56.111 &45C F R46.111(Applicable Cr iteria M et)

D 21CFR50.23 &45CFR.116(Waiver or Alteration of Consent Process)

D 21CFR50.27 &45CFR46.117(Waiver of Consent Documentation)

D 45CF R46-Subpart B(Research I nvolving Pregnant Women or Fetuses)

D 45CF R46-Subpart C(Research Involving Prisoners—Indicate Level of Risk, e.g. Mi nimal orGreater Than Minimal)

D 21C FR 50 & 45CF R46-Subpart D(Research I nvolving Children—Detail I nclusion or E xclusion J ustificationand Indicate Level of Risk, e.g. Minimal or Greater Than Minimal,Describe Consent Requirements as Specifi ed in 21CFR50.55 and

45CFR46.408)

Determinations and J ustifi cations Required by Regulations and Guidelines;N one

I RB Decision: Approve Continuing Renewal



Vote Yes: No: 0 Abstain: 0 Not Present:


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Date: 02/07/2011To: S. Charles, Schulz ([email protected])

From: [email protected]

Subject: #STUDYNBR#- PI #PI LASTNAME #- IRB - APVD Continuing Review

Message: TO : [email protected], [email protected], [email protected], [email protected],

[email protected], [email protected], [email protected],

The IRB: Human Subjects Committee renewed its approval of the referenced studylisted below:

Study Number: 0709M16844Principal Investigator: Sellmann SchulzExpiration Date: 01/25/2012Approval Date: 01/26/2011Title(s): Seroquel XR for the Management of Borderline Personality Disorder: A

Randomized Double-Blind Comparison with Placebo

This e-mail confirmation is your official U niversity of Minnesota HRPP notification ofcontinuing review approval. You will not receive a hard copy or letter. T his secure

electronic notification between password protected authentications has been deemed by

the University of Minnesota to constitute a legal signature.

You may go to the View Completed section of http://eresearch.umn.edu/ to view orprint your continuing review submission.

For grant certification purposes you will need this date and the Assurance ofCompliance number, which is FWA00000312 (Fairview Health Systems Research

F W A 00000325, G ill ette C hildrens Specialty H ealthcare F W A 00004003). Approvalwill expire one year from that date. You will receive a report form two months before

the expiration date.

In the event that you submitted a consent document with the continuing review form, ithas also been reviewed and approved. I f you provided a summary of subjects'experi ence to include non-UPI RT SO events, these are hereby acknowledged.

As Principal Investigator of this project, you are required by federal regulations to

inform the IRB of any proposed changes in your research that wil l affect humansubjects. Changes should not be initiated until written IRB approval is received.Unanticipated problems and adverse events should be reported to the IRB as theyoccur . Results of inspections by any external regulatory agency (i.e. PDA) must bereported immediately to the IRB . Research projects are subject to continuing review.

I f you have any questions, please call the IRB office at (612) 626-5654. The IRBwishes you continuing success with your research.


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Continuing Review of I RB - PendingMedical Research

Review Period:12/03/2010-01/25/2012

R ev: 03/01/200?

Study N umber: 0709M 16844Principal I nvestigator: Sellmann C SchulzTitle(s): Seroquel XR for the Management of Borderline Personality Disorder:



Funding Source(s)F unding Source: ASTRA ZEN E C A IN TLF unding Type;

PersonnelSchulz, Sellmann (P. I .)


Cullen, Kathryn (Co-lnvestigator)

Man, Georges-J akob (Staff/Lab)

H ourj, Al aa (Staff/L ab)




R oots, M onik a (Staff/L ab)


50~ ~~~ ' - ' ' -•- ---- -- -—' • | tota enr o l ed 3 4


Ma eFema eUnknownTota

ENumber of subjects

M a l err

I:enrolled to

Female

K

3Edate;

Unknown

, 10:

14|

Total14~

The University of Minnesota I s.an equal opportunityaducatorS, employer. ' Page 1©2004 by the Regents ofthe University of Minnesota.


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Yes

T otal nati onal accmal to date; 60

Unanticipated Problem ReportingSince the most recent I RB continuing review apppoval, have g>ny participants withdrawn from theresearch?

Yes

There have been 4 early withdrawals, al l due to adverse event: sedation,

Since the most recent IRB continuing review approval, have any participants complained about theresearch?

No

Have any serious and unanticipated problems been reported to the IRB?

N o

Study SummarySummarize preliminary iriformatlon about any results ancl/or trends;

One of 3 participating sites wi thdrew from the study early in 2011, M cLean H ospital at H arva rd U niversity, pl M aryZanar inl, T he site withdrew due to inability to enroll subjects. The 2 remainin g sites,D of M N & D of I owa, w ill becompleting the enrollment goal of 99 total subjects.

Have there been any changes in protocol approved by the I RBsince last continuing review?

No

Sincethe most recent I RB continuing review approval, have there been anyi progress reports on theresearch?

No

Since the most recent I RB continuing review approval, have there been any multi-center trial reports?

No

Since the most recent I RB continuing review approval, have there been any other informationrelevant to this research dificovered, especially information about the risks and benefits associatedwith the research?

No

The University of Minnesota is an equal opportunity educator& employer. Page 2©2004 by the Regents of (he Universi ty of Minnesota.


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Since the most recent I RB confinuing review approval, have subjects experienced any benefits?

Yes

Some subjects have reported reduction I n th eir symptoms of B orderli ne P ersonal ity D isorder,

External FindingsI s there anything in the relevant recent I itergfure that the IRB should know about concerning'thisresearch?

No

Consent/Assent/HI PAA FormsHave there been any changes to the consent and/or assent form (s) since the .last I RB approval?

No

Have translated consent short forms been usecl in conjunction with an interpreter to obtain consentfor th is study?

No

Other Comments

W e hope to complete enrollment for the study in 1 year ^

The'University of Minnesota is:an equal opportunity educator & employer- Page 3©2004 by the Regents of the University of Minnesota.


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MemoTo: S. Charles Schulz, M.D.

From: Scott Crow, M.D.

CC; Kyle Rudser Ph.D., and Kathy Mischke

Date: 11/8/2011

Re: Seroquel X R BP D Study Safety M onitoring M inutes

Safety monitoring and enrollment dgta were reviewed to date and the following werenoted.

1. Tjme to data entry has dJ minjshedi substantially, particularly at the Minnesotasite with the median now approaching 10 days. This is extremely useful foradequate and timely safety monitoring.

2. I t was noted previously that one subject at the Iowa site had weight gain ratedat mild but recorded as an SAE; it had been requested that this be clari fiedand likely corrected. This has not yet been done but needs to be done.

3, Baseline safety data are now present for all newly enrolled subjects which alsorepresents gn important improvement,

4. A substantial number of AE s have a severity rating: of "unknown". In order tofacilitate safety monitoring, severity ratings need to be clarified and gssignedto these AE s.

5. As noted previously, it appears that screen fails are being tracked and enteredinfo the data base at the I owa site but they are not be entered at theMinnesota site (unless in fgct there are truly no screen fails which seemsunli kely). U ltimately it is of greatest importan t simply tha t these be trackedand entered somewhere as they will undoubtedly be needed for reporting trial

results ultimately. On the other hand they are being entered at the Iowa siteand it would be best to handle this consistently across sites, by themechanism of entering them for the Minnesota site as well.


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P: SchuzUn vers tyof MnnesotaHSC# 0709M16844 Human Research Protection ProgramRevewer: QucH I nst i tui onal RevewBoard

M eeting Date: 11/16/2011

Ful l Committee Review—Continuing Review of Approved ResearchI 'I

"An 1KB shall conduct coi-itiiitiiiig review of research mvet'ed by this policy at intervals appropriate to the- degree ofrisk, but not less than once per year, and shall have the authority to observe or have a third party obsen'e theconsent process and the research," 21CFR56.109 and 45CFR46,109

"Cantiming review of research must be substantive and meatsingfiil." OHRP Guidance 1-15-07I • ••

Short T itle: Seroquel X R for the M anagement of Borderl ine P ersonali ty Disorder

Enrollment: [X] Open d Closed Q On holdTreatment: [X] Continues Q Complete Q "Not a treatment studyFollow-up: [3 Continues 0 Complete Q N o follow-up required

Funding: D Federal | 1̂ Industry Sponsored d Foundationm Departmental Q Noile

Enrollment Numbers: Approved: 50 Enrolled: 34 Years active: 4

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others);Have any UPI RT SOs been reported In the last year? Q Yes CX] NoAre there concerns to be discussed by the Committee? Q Yes [̂ N o

Study Summary; :[X] Adequate D DeficientQ TSI one - too early Q None - data analysis elsewhere

External Findings: ̂DgMB letter Q Progress report D Action letter

Consent and Assent F orms: [X]; Submitted D Missing Q Waived or not applicable

HI PAA Forms: ̂ Submitted D M issing Q Waived or not applicable,D Closed to enrollment - forms are w longer pertinent

Are all persons listed on consent form also li sted in the mB records? [̂ Yes Q No

Inclusion of Child fen in Research:I f children are included in this research confirm that they should still be included.

D Yes D No IEI NA - children excludedI f chil dren are Included, is there new inforrnation which affects the regulatory classification

(45C F R46 Subpart D ) indicate the cihange.

D (404) M inimal ri skD (405) Gr eater than mi nimal ri sk; but h olds prospect of direct benefits to subjects,D (406) Gr eater than mini mal ri sk; no prospect of direct benefit to subjects, but li kely toyield generaU zable kncnyledge about the subject's disorder QI ' conditioti,

University ofMumesotaIRBConttnumg Review FormV ersion October 2010


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Substantive Changes: I f any of the following are evident from the eontinuing review report,describe the changes for Committee diseussioti.

0 Change iti risk or benefit

0 Change In subject populationQ Min6r changes in consent form

Major changes in consent form

C hange in fundingChange in coiiflict of interestChange in data management

I tems for Committee Discussion:P l reports that the H arvard site dropped out, leaving only U ofM and l& wa,

Recommended Stipulations:1. For continuing review, i t i$ reported that 34 subjects have been enrolled, but the D8M B r eport notes thatscreen failures have not been registered in the study database. Confirm whether the sum of 34 enrolieesincludes screen fai lur es.2. Update the out-of-study contact address.

Recommended Suggestions:1. Considering that D of M has enrolled 57% of subjects, the nati onal goal is 99 subjects, and the localall owance is 50 subjects, i t may be necessary to increase the local all owance,2. On page 2 of the consent form, update the number of study sites from "3" to "2".

Recommended Action: Q Approve as SubmittedApprove with SuggestionsApprove with Stipulations as noted

1 Response to original reviewer

R̂esponse can be reviewed by IRE staffQ Approval Deferred - additional information required

Continuing Review Interval: Kl AnnuallyD E very 6 months

Quarterlya Other interval:

/ have completed a substarnive and mecinmgful review based on the information made. availcibleat this time.

Print name of reviewer: Donald C, QilicH Date: 11/16/2011


I f you choose to submit this form eleptronically, please send to irhfTOtim.edu.Forms submitted from a unin.edu account do n&t need a hard-copy signature.

University of Minnesota IRBGontiliumg Review FormV ersion October 2010


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Committee Meeting Minutes

November 16, 2011

Agenda I tem;Continuing Review-IVI edical

Agenda I temi None

Agenda Item ̂ None

Kt: Schulz, Sellmann IR.evievyer̂ Quick

IRevieyrer; 3None

Protocol Title and̂ HSC Ŝ̂ 'SeroîA^Randomized;Double-Blma'Gomp:ayiŝ

I tem Description:Wonê11.-71®

Di scussion of C ohtrovertedlssues Summary;

There were no contr overted issues.

tRevisionŝ :Clari fl (̂ tibr is:o)ĉ Stipul ations;;:;̂ ;j;̂ :';l:":̂ ^̂^̂^̂ ̂':;l'l l:'̂ ?/''?'̂:l î '̂ "'':lll:;l ':̂

I t appears as though this study has enroll ed a total of 34 subjects. Is this correct? The DS MB r eport notesthat screen failures have not been registered in the study database. Confirm whether the sum of 34 enrollees includesscreen failures.

[Change in Risk/Bemefit Balance;N one

Committee Must Address:

E l 21CF R56.111 & 45CF R46.111(Applicable Criteria M et)

D 21CFR50.23 & 45CFR.U6(Waiver or Alteration of Consent Process)

D 21CF R50.27 & 45CF R46.117(Waiver of Consent Documentati on)

D45CFR46-SubpartB(Research Involving Pregnant Women or Fetuses)

D 45CF R46-Subpart C(Research Involving Pri soners—Indicate Level of Risk, e.g. Mi nimal orGreater Than Minimal)

D 21CFR 50 & 45CFR 46-Subpart D(Research I nvolving Children—Detail I nclusion or E xclusion J ustificationand I ndicate Level of Risk, e.g. Minimal or Greater Thau Minimal,Describe Consent Requirements as Specified in 21CFRS0.55 and45CF R46.408)

Determinations and J ustifications Requir ed by Regulations and Guidelines:None

I RB Decision:Approve Continuing Review with Stipulations



Vote Yes: B No: 0 Abstain: 0 Not Present:

Members Not Present for Vote Due to Conflict of I nterest: Crow


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11/21/2011

Sell tnann C Schulz

P sychi& try, D ept of8393AF282/2AWest-B2450 Riverside AveMinneapolis, MN 55454

RE : "S r̂oquel XR for the Management of Borderline Personality Disorder: A RandomizedDouble-Blind Comparison with Plaeebo"IRB Code Number: 0709M16844

Dear Dr. Schulz,

A t the meeting on N ovember 1$, 2011, the Instituti onal R eview B oard (I R B) r eviewed andrenewed approval for the referenced study. The IRB stipulated the following:

• K appears as though this study has enroll ed a total' of 34 subjects. I s this correct? TheDSMB report notes that screen failures have not been registered in the study database.Confirm whetlier the sum of 34 enrollees includes screen failures.

Please provide a response for I RB review.

I f your response is not received within ninety days, the study wil l be filed inactive.

Please send your response to HRPP (Mayo Mail Code 820; D-528 Mayo Memorial Bmlding;420 Delawar e St. SE ; M inneapolis, M N 55455), T he signature of the P rin cipal I nvestigator isthe only signature required with the response, Only one copy of the response is necessary.


Sincerely,

Felicia. Mroczkowski, CIP

Research Compliance SupemsorFM/mq

CC; Scott Crow, Kathryn Cullen, Michael Mil ler, Richelle Moen, Ann Romine


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Continuing Review of I RB - Pending

Medical Research

Review Period;10/21/2011-11/14/2012

R ev; 03/01/2005

Study N umber: 0709M 16844Principal I nvestigator: S Charles SchulzTitle(s): Seroquel XR for the Management of Borderline Personality Disorder:



Funding Source(s)Funding Source: AST RA ZEN E C A IN TLF unding Type:

PersonnelSchulz, S Charles (P. I .)

C arlson, W illiam (Staff/La b)


Cullen, Kathryn (Co-lnvestigator)

Davis, Aubrey (Staff/Lab)

F ryza. Br andon (Staff/Lab)

HanG/ L ab |

He e, Mnka( Saf / Lab|

Houri, Alaa (Correspondent)




Stepka, M egan (Staff/Lab)

W atroba, L exa (Staff/L ab)

Investigational Drug(s)

The University of Minnesota is an equal opportunity educators employer- page 1©2004 by the Regents of the University of Minnesota.


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IND Number: 45,456IND Holder: AstraZeneca Pharmaceuticals L P (Sponsor)


50

Number of subjects enrolled this reporting period:

Ma eFema eUnknownTotaR~

Number of

Malef20-

subjects

Kenrolled to

FemaleT35~

~J £date:

Unknown

10 C

1̂3

Total55_

]

\I


Yes


Unanticipated Problem ReportingSince the most recent I RB continuing review approval, have any participants withdrawn from theresearch?

Yes

4 earl y withdrawals since last continuing review. 2 were due to adverse events, 1 was due to inefficacy, and 1 wasdue to subject moving away. 3 screen failures since last Gontinui ng review.

Since the most recent I RB continuing review approvali have any participants complained about theresearch?

No

Have any serious and unanticipated problems been reported to the IRB?

Yes

13 J UL 2012 - UPIRTSO report date 06 AUG 2012- Submission acknowledged by IRB No changes to consentform or study were needed.

Study SummarySummarize preliminary infonnation about any results and/or trends:

W e are nearing the end of ow enrollment for th is study. Our total enrollment for both al l 3 sites will beapproximately 90 subjects (this total does not include screen failures). All subjects will have completed study by theend of 2012 or early 2013.


The University of Minnesota is an equal opportunity educator & employer- Page 2©2004 by the Regents of the University of Minnesota.


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Yes

M R I a ddendum an d M R I h ealthy contr ols w ere added to the main stu dy. Consents documents wi ll be uploadedhere.


N o

Since the most recent I RB continuing review approval, have there been any multi-center trial reports?

No

Since the most recent I RB continuing review approval, have there been any other informationrelevant to this research discovered, especially information about the risks and benefits associatedwith the research?

No


Yes

Some subjects have reported a decrease in their symptoms of Borderl ine Personali ty Disorder.

External FindingsI s there anything in the relevant recent literature that the I RB should know about conGerning thisresearch?

No

Consent/Assent/HI PAA FormsHave there been any changes to the consent and/or assent form(s) since the last I RB approval?

Yes

The main study consent was updated and approved by the IRB on Aug 9,2012.

Have translated consent short forms been used in conjunction with an interpreter to obtain consentfor this study?

No

Other Comments

The University of Minnesota is an equal opportunity educator & employer- page 3©2004 by the Regents of the University of Minnesota.


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P: SchuzUn vers tyof Mnn esotaHSC# 0709M16844 Humaa Research Protection ProgramRevewer: Quck I nst i tui onal RevewBoardMeeting Date: 10/31/12

Full Committee Review—Continuing Review of Approved ResearchI

"An 1KB shall conduct continuing review of research covered by this policy at Intervals cippropriateto the degree ofrisk, but not less than once per year, and shall have the authority to observe or have a third party observe theconsmt process and the research." 21CFR56.109and45CFR46.109

"Coittinuing review of research must be substantive and meaningful ." OHRF Guidance 1-15-07

Short T itle: Seroquel X R for the M anagement of Borderl ine Personali ty Disorder

Enrollment; [X] Open Q Closed D On holdTreatment: ̂Continues Q Complete Q Not a treatment studyFollow-up: 13 Continues Q; Complete Q N o follow-up required

Funding: C] Federal ^ : Sponsored Q Foundation D Departmental

Enrollment Numbers: Approved; 50 Enrolled; 55 Years active; 6

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others):Have any UPI RT SOs been reported in the last year? ̂Yes D N oAre there concerns to be discussed by the Committee? | _| Yes D>3 No

Study Summary: Q Adequate d Deficient[X] None - too early Q Notte - data analysis elsewhere

t

External Findings; QDSMB letter D Progress report D Action letter

Consent and Assent F orms: ̂ Submitted Q Missing Q'Waived or not appl icableHI PAA FOrmS: D Submitted ̂ Missing D Waived or not applicable

0 Closed to enrollment - forms are no longer pertinentAre all persons listed on consent form also listed on the IRB roster? [̂Yes D No

I nclusion of Children in Research:I f children ar e included in this r esearch confirm that they should stil l be included.

Yes D No | EI NA - children excludedI f children are included this ii iGlusion must meet one of the following criteria for risk/benefitassessment according to federal regulation (2ICFR56 and 45CFR46 Subp̂rt D),

(404) M inimal risk(405) G reater th an mini mal ri sk; but holds prospect of direct benefits to subjects,

Q (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely toyield generalizable knowledge about the subject's disorder or condition,

University of Minnesota I RBContinuing Review FormV ersion 10/27/09


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Substantive Changes: If any ofthe following are evident from the continuing review,describe the changes for Committee discussion,

Change inrisk or benefit Q Change in fundingChange in. subject population | _j Change in conflict of interest

D Minor changes in consent form Q Change I n data managementMajor changes in consent form

I tems for Committee Discussion:M RI was added in the last year. C fintrol subjects were added in the last year.

Recommended Stipulations:1. Our records indicate that 50 subjects were approved for the study but 55 have been enrolled. Explainhow over-enrollr nent occurred and measures taK en to prevent recurr ence, inform the IRB how manysubjects are required and provide justification,2. Submit a 5-yr renewa l.3. Update the out-of-study contact address in the.main consent form for pati ents.4. Submit a current HI P AA form.

Recommended Suggestions:

Recommended Action: Q Approve as SubmittedQ Approve with Suggestions

Approve with Stipulations as notedResponse to original reviewer

[>


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Committee Meeting MinutesOctober 31,2012

Agendaltem:Continuing Review-J VIedical

Agenda I tem: None

A ênclâ tem: None

PI : Schulz, S Charles R eview er; ^ Qu ick

Reviewer: None

Protocol Title and HSC :̂"Seroqu^̂ARandpmizedDduI llêutdComparteonwithPlhacebo''̂

I tem Description:Time for 5 year renewal.

iD iscussidn of Contt-overted I ssues Sumimary:


]RevsonS). Carifl


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Committee Meeting MinutesOctober 31,2012

I RB Decision:

Approve Continuing Review with Stipulations



Vote Yes: | No: 0 Abstain: 0 Not Present:

Members Not Present for Vote Due to Conflict of I nterest: None


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November 5,2012

S Charles SchulzPsychiatry, Dept of

F282/2AWest-B8393A2450 Riverside AveMinneapolis, MN 55454

RE : "Seroquel XRfor tile Management of Borderline Personality Disotder; A RaiidomizedDoubleB̂l ind Comparison with P laceboIRB Code Number: 0709M16844

Dear Dr. Schulz,

At the meeting on October 31,2012 the Institutional Review Board (I RB) reviewed and renewedapproval for the referenced study. The'I RB stipulated the following;

• Til e Fairview Research H elpline office moved off-campus as of M ay 7,2011. The telephonenumber is unchanged; however, please correct the address in tile Contacts and Questions sectionof all consent forms, This section should read; "If5?ou have any questions or concerns regarding

the study and W ould lik e to talk to someone other th an th e researcher(s), you ar e encour aged tocontact the Fairview Research H elpline at telephone nuinber 612-672-7692 or toll free at866-508-6961. You may also contact fliis office in writing or m person at Fain'iew Research

AdmMstmiion, 243 3 Energy Park Drive, St. Paid, MN 55108"• I n response to evolving federal guidelines and increased scrutiny by regulators, the IRB must in

some cages reconsider studies ori ginally reviewed over 5 years ago. To ensure that the IRB has

accurate informati on, investigators are required to provide a five year renewal •fonn for thesestudies. Since the original application of this study dEites from September 20,07, you ate asked to

complete a- five year renewal form. T he most cuft'ent form catt be downloaded firotti our web siteat; http://www.research.umn.edu/irb/fom-is.htm]. Provide the five year renewal form within 90

days.

• Pl ease submit a current HI PAA form.

Please provide a response and revised consent form for I RB review.

I f your response is not received w ithi n ni nety days, the study wi ll be filed inactive.

Please send your electronic response to HRPP ([email protected]). The signature of the Principal

I nvestigator is the only signature required with the response. Only one copy of the response is necessary.I f you have any questions, please contact the IRB office at 612-626-5654.

Sincerely,

6̂f̂Fe c aMoczkowk CP |Research Compliance SupervisorFM/acCC: Scott Crow, Kafhryu Cullen, Alaa Houri, Michael Miller, Richelle Moen, Ann. Roltiine


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UNI VE RSITY OF MI NNESOTA RECD NOV 2 Q 2012

TwnCti es Campus Ambuat oryRe&ewch Ce nter F2S2 2AWst

Depa r t ment of PsycMMywowvŵeŵe^M hmeapolis, M N 55454Medical SchoolOffi ce: 612-626-5001

November 20, 2012

F elicia M roczkowskiI nstitutional Review BoardU niversity of M innesotaMayo Mail Code 820D528 M ayo M emorial B uilding420 Delaware Street S.E.Minneapolis, Minnesota 55455

RE : "Seroquel XR for the management of Borderl ine Personality Disorder (BPD)"H SC #0709M 16844

Dear Felicia;

Thank you for your Continuing Review of the referenced study. We are responding toIRB stipulations as stated in your letter dated November 5, 2012.

1) T he consent form has been updated to include the correct address in, the GontQOtsand Questions section on page 9.

2) We have completed the IRB Five Year Renewal F orm,

3) We are submitting the current HtPAA form, version date 24 FEB 2009. No changeshave been made to the HIPAA form,

The following documents are enclosed;1. Consent form version date 20 NOV 20122. IRB Five Year Renewal Form3. HIPAA form version date 24 FE B 2009

Thank you and please contact Ann Romine, study coordinator, with any questions at612-626-6812.

Sincerely,

i Û M A^S. Charles Schulz, MDprincipal I nvestigator


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U N I V E R S I T Y OF M I N N E S O TA

Five Year Renewal

Route this form to;

See instructions below.Rev; 10/1/09

I nstructions:Use this form whensubmftting for five-year renewal on I RB profocpls,

), Submit this form to the Research Subjects' Proteaions Programs Office:

U.S. Mail Address:Human Research Protection Program

M M C 820420 Delaware St. SEMinneapoli s, MN 554S5-0392

I RB Protocol I nformation

Campus M ail:Human R6seareh Protection Program

M M C 820'Minneapolis Campus

Deliver to;D-528 M ayo M emorial B uildingMinneapoli s Campus8-4:30, M-F

IRB Study Number:C urrent P rincipal Investigator;

Primary Title:

0709M 16844S, Charles Schulz, MDSeroquel XR for the Management of Borderline Personality Disorder (BPD)

1. State the original hypothesis or research question in a few short sentences:

T he hypothesis of this proposal i s that Seroquel X R w il l be stati stically superior to placebo inthi s controlled teial. A double-blind, placebo-controlled randomized tri al is proposed to test

the efficacy and safety of Seroquel XR, A fixed dose strategy wil l be employed - 150 mg/dand 300 mg/d.

2. Summarize any major changes to this study in the past five years. F or instance, describe any new findings, any significantchanges in the protocol or project design, indicate any changes in study personnel;

1) The Brain I maging

seroquel xr for borderline personality disorder continuing review, university of minnesota irb

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