Prilosec1® 20 mg TabletsRx to OTC Switch

Daiva Shetty, M.D.

Division of Over-the-Counter Drug Products (HFD-560)

Food and Drug Administration1

Prilosec1® Rx to OTC Switch: Overview

• Regulatory History

• Proposed Label

• Target Population

• Actual Use Study #007

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Differences Between the Original and Resubmission NDA

Original Resubmitted

Dose 10 mg 20 mg

Target Population > 12 years > 18 years Anybody with HB HB > 2 x/week

Uses Relief and prevention Prevention of frequent HB

Duration 10 days 14 days(intermittent) (continuous)

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Overview of the Program

• Actual Use Study– #007

• Three Label Comprehension Studies– #02255– #12179– #17859

• Proposed OTC Labeling• Safety Update

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Prilosec1® Rx to OTC Switch: Overview

• Regulatory History

• Proposed Label

• Target Population

• Actual Use Study #007

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Proposed Label: Uses

• for prevention of the symptoms of frequent heartburn for 24 hours

• only for those who suffer heartburn two or more days a week

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Proposed Label: Directions

Adults 18 years of age or older:• for prevention of frequent heartburn, swallow

1 tablet with a glass of water in the morning• take every day for 14 days• do not continue beyond 14 days unless

directed by your doctor. If your frequent heartburn continues or returns, it could be a sign of a more serious condition.

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Proposed Label: Warning

Heartburn warning. Heartburn can be a sign of a more serious condition. Notify your doctor if you have had heartburn for 3 months or longer without talking to your doctor.

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Prilosec1® Rx to OTC Switch: Overview

• Regulatory History

• Proposed Label

• Target Population

• Actual Use Study #007

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OTC Issues for Prilosec1®

Are consumers able to:• self-select/de-select

– identify risk factors• self-treat

– follow label directions for dosing and duration of use

– follow label directions when to see their HCP

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Actual Use Study #007: Study Design

• Multi-center

• Open-label

• All-comers

• Minimal inclusion/exclusion criteria

• 3-month duration

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Primary Objective

How consumers use omeprazole in naturalistic OTC conditions following proposed labeling instructions

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Results: Self-SelectionParticipated in a self-selection interview 1,301

Answer not available 1Self-selected product “Not appropriate” 49

Self-selected product “Appropriate” 1,251(Self-Selection Population)

Answer not available 1Subject < 18 years of age 3Chose not to participate 384

Chose to participate 863

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Chose Not to Participate N=384

• Study participation inconvenient 115• Don’t try new medicine without

MD approval 104• Happy with current HB medication 32• Too expensive 19• Don’t use medication 5• Other 113

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Chose to Participate N=863

Did not meet study criteria 9Purchased study medication 854

Did not return any diaries 92Lost to follow-up 82Withdrew consent 8Adverse event 1Investigator decision 1

Returned one or more diaries 762

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Returned One or More Diaries N=762

Returned blank diaries 4Returned diaries & used study drug 758(Treated population)

Not available for 3-month follow-up 109Available for 3-month follow-up 649

Subject Disposition: Summary

T re a te d P o p u la tio n(N = 7 5 8 )

C o m p le te d th e S tu d y b y R e tu r n in g D ia r ie s(N = 7 6 2 )

P u r c h a se d S tu d y M e d ic a tio n(N = 8 5 4 )

D ec id e d to P a r tic ip a te(N = 8 6 6 )

S ta te d th a t P r ilo se c 1 is A p p r o p r ia te fo r T h e m to U seS e lf-S e le c t io n P o p u la tio n

(N = 1 ,2 5 1 )

P a r tic ip a te d in S e lf-S e le c t io n In te r v iew(N = 1 ,3 0 1 )

Excluded from Study(N=12)+

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Demographics

(Self-Selection Population N=1,251)

• 59% Females• 16-91 Years of age, mean 48• 65% Caucasian• 18% Black • 2% Asian• 1.2% American Indian• 9.4% Low Literacy Group

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Heartburn History: Duration

(Self-Selection Population N=1,251)

< 3 months 29 (2.3%)

4-12 months 99 (7.9%)

1-2 years 238 (19%)

3-5 years 314 (25%)

> 5 years 567 (45%)

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Heartburn History: Frequency

(Self-Selection Population N=1,251)

< 1 day a week 169 (14%)

2-3 days a week 425 (34%)

4-5 days a week 164 (13%)

6-7 days a week 489 (39%)

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Consultation for HB with Health Care Provider (HCP): Definition

• Advice from a physician or supporting HCP, or

• Use of a prescription HB medication

• The contact was not confirmed

• Specific information was not collected (what issue was discussed and what advice was given)

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Consultation for HB with HCP

Self-Selection Population (N=1,251)

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over 1 year(17%)

within 1 year(46%)

never(37%)

Correct Self-Selection: Definition

• HB > 2 days/week

• > 18 years old

• Not pregnant/lactating

• Not allergic to omeprazole

• No contraindicated symptoms that were not reported to HCP

• No contraindicated medications that were not discussed with a HCP

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Correct Self-Selection: ResultsSelf-Selection Population (N=1,251)

Correct 76% (n=961)

Incorrect 24% (n=290)• HB < 1 day/week 169

• Contraindicated symptoms 134

• Contraindicated medications 15

• Age < 18 years 3

• Pregnant or nursing 1

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Purchasing Patterns

Purchase Population (N=854)

• 94% (799) 1 carton*• 2% (20) 2 cartons• 1% (8) 3 cartons• 3% (27) 4 cartons

* Each carton contained 14 tablets

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Compliance with Labeled Directions

Treated Population (N=758)

Compliant 478 (63%)

Not compliant: 280 (27%)

Exceeded 1 dose per day 69 (9%)

Exceeded 1 tablet per dose 31 (4%)

Exceeded 14 consecutive days 23 (3%)

Took for less than 14 days 249 (33%)

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Return of Frequent HeartburnTreated Population available for 3-month follow-up (N=649)

• 43% (n=276) Did not have HB• 57% (n=373) Frequent HB returned:

– 46% (171) Antacid HB medicine – 27% (99) Rx HB medicine– 21% (78) OTC acid reducer– 20% (75) Consulted HCP– 10% (36) Changed lifestyle– 6% (22) Did not do anything

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Study Limitations

• Relatively short duration (3 months)

• Did not address if Prilosec1 will be used intermittently (few courses over a year)

• Did not address the concomitant usage of other HB medications

• Did not assess if consumers understand that Prilosec1 is not for relief of acute HB

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Actual Use Study: Conclusions

• Most of the consumers who self-selected Prilosec1 as appropriate for their use had a long history of frequent HB

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Overall Conclusions (cont.)• Even though the label stated to see HCP prior to the

use of Prilosec1, 1/3 of the subjects did not do so

• More than half of the treated population had their HB return:– Majority switched to other HB medicine (Rx or OTC)

– 1/5 went to see their HCP

• Unclear how the interaction with HCP prior or after the use of Prilosec1 would have influenced consumer behavior

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Overall Conclusions (cont.)

• Prilosec1 is likely to be used by consumers with contraindicated symptoms

• Prilosec1 is likely to be used by consumers with infrequent HB

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