Pediatric Trials NetworkPediatric Trials Network

What Is The Pediatric Trials Network PTN?What Is The Pediatric Trials Network PTN?

Sponsored by the Eunice Kennedy Shriver National Institute of Sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Child Health and Human Development (NICHD)

The primary objective of the Pediatric Trials Network:The primary objective of the Pediatric Trials Network:

Create an infrastructure for investigators to conduct trials that improve Create an infrastructure for investigators to conduct trials that improve pediatric labeling and child health.pediatric labeling and child health.

PTN is studying product formulation, drug dose, efficacy, safety, PTN is studying product formulation, drug dose, efficacy, safety, and device validation and device validation

Evidence of success will be completed trials that improve dosing, Evidence of success will be completed trials that improve dosing, safety information, labeling, and ultimately child healthsafety information, labeling, and ultimately child health

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Structure of PTNStructure of PTN

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Pediatric Trials Network (PTN) 2011Pediatric Trials Network (PTN) 2011

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Protocol Title: Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants

Objective: Evaluate the safety, PK, and surrogate PD of intravenous metronidazole in premature infants with suspected serious infection

Study Population:16 to 32 participants <32 weeks gestational age with suspected serious infection. Participants will be divided into 2 groups based on postnatal age.

Study Duration: original target 18 months (finished in 12); each participant will participate in the study for up to 15 days: 2-5 days of study drug administration followed by 10 days of adverse events monitoring.

Number of Sites: 3

October, 2011 Enrollment Complete

Protocol: Metronidazole Protocol: Metronidazole Protocol Chair: Cohen-WolkowiezProtocol Chair: Cohen-Wolkowiez

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Demographic Distribution: Demographic Distribution: These data have not been peer-reviewedThese data have not been peer-reviewed

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Metronidazole Individual EBE PK Parameter Estimates by Metronidazole Individual EBE PK Parameter Estimates by Post Natal Age Group: Post Natal Age Group:

These data have not been peer-reviewedThese data have not been peer-reviewed

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Concentration vs. Time: Concentration vs. Time:

These data have not been peer-reviewed These data have not been peer-reviewed

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Clearance vs. Post Menstrual Age: Clearance vs. Post Menstrual Age:

These data have not been peer-reviewedThese data have not been peer-reviewed

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Protocol: Acyclovir Protocol: Acyclovir Protocol Chair: SmithProtocol Chair: Smith

Protocol Title: An Open Label Study to Describe the Protocol Title: An Open Label Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants Pharmacokinetics of Acyclovir in Premature Infants

Objective: To evaluate the safety and PK of IV acyclovir in Objective: To evaluate the safety and PK of IV acyclovir in premature infants with suspected systemic infections. premature infants with suspected systemic infections.

Study Population: 20 Infants < 45 days postnatal age, suspected Study Population: 20 Infants < 45 days postnatal age, suspected to have a systemic infection divided into groups by gestational and to have a systemic infection divided into groups by gestational and postnatal agepostnatal age

Study Duration: each infant will be in the study for up to 13 days; Study Duration: each infant will be in the study for up to 13 days; goal is to provide final component of PK data for subsequent goal is to provide final component of PK data for subsequent efficacy trialefficacy trial

Number of Sites: 3Number of Sites: 3

First Patient Enrolled: September 19, 2011; target March 2012 First Patient Enrolled: September 19, 2011; target March 2012

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Protocol: HydroxyureaProtocol: HydroxyureaProtocol Chair: NevilleProtocol Chair: Neville

Protocol Title: PK & Relative Bioavailability of a Liquid Formulation Protocol Title: PK & Relative Bioavailability of a Liquid Formulation of Hydroxyurea in Pediatric Patients with Sickle Cell Anemiaof Hydroxyurea in Pediatric Patients with Sickle Cell Anemia

Objective: relative bioavailabilty study and bioequivalence study Objective: relative bioavailabilty study and bioequivalence study with new formulationwith new formulation

Study Population: 40 children ages 2-17 with sickle cell anemia or Study Population: 40 children ages 2-17 with sickle cell anemia or sickle beta-zero thalassemia; two-armed study with older children sickle beta-zero thalassemia; two-armed study with older children (bioequivalence) enrolled first(bioequivalence) enrolled first

Study duration: a subset of patients in each age cohort will receive Study duration: a subset of patients in each age cohort will receive single dose and a subset will receive multiple dosessingle dose and a subset will receive multiple doses

Number of Sites: SixNumber of Sites: Six

First Patient: December, 2011First Patient: December, 2011

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Protocol Title: Pharmacokinetics of Understudied Drugs Protocol Title: Pharmacokinetics of Understudied Drugs Administered to Children per Standard of CareAdministered to Children per Standard of Care

Objectives:Objectives: Evaluate the PK of understudied drugs currently being administered to

children.

Study Population: 500 children (birth-20 years) who are Study Population: 500 children (birth-20 years) who are receiving understudied drugs of interest per standard of receiving understudied drugs of interest per standard of care as prescribed by their treating caregivercare as prescribed by their treating caregiver

Study Duration: each child will participate in the study for Study Duration: each child will participate in the study for up to 90 days per drug; study conduct for 3 yearsup to 90 days per drug; study conduct for 3 years

Number of Sites: 15Number of Sites: 15

First Patient Enrolled: November, 2011First Patient Enrolled: November, 2011

Protocol: POPS Pediatric Opportunistic PK StudyProtocol: POPS Pediatric Opportunistic PK Study

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Protocol: LisinoprilProtocol: LisinoprilProtocol Chair: TrachtmanProtocol Chair: Trachtman

Protocol Title: Safety and Pharmacokinetics of Protocol Title: Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant RecipientsLisinopril in Pediatric Kidney Transplant Recipients

Objective: initial description of the PK-PD and safety of Objective: initial description of the PK-PD and safety of lisinopril following transplantationlisinopril following transplantation

Study population: 24 children ages 2-18 with kidney Study population: 24 children ages 2-18 with kidney transplant and stable allograft functiontransplant and stable allograft function

Study participation: Up to 51 days; enrolled children will Study participation: Up to 51 days; enrolled children will receive multiple doses with multiple assessments for receive multiple doses with multiple assessments for potential endpoints for subsequent efficacy trialpotential endpoints for subsequent efficacy trial

Number of Sites: 8Number of Sites: 8

Target to Enroll First Patient: January 2012Target to Enroll First Patient: January 2012

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Protocol: TAPEProtocol: TAPEProtocol Chair: RahmanProtocol Chair: Rahman

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Protocol Title: Taking the Guesswork out of Protocol Title: Taking the Guesswork out of Pediatric Weight Estimation (TAPE): Validation Pediatric Weight Estimation (TAPE): Validation of the Mercy TAPEof the Mercy TAPE

Objective: device trial to provide more accurate, Objective: device trial to provide more accurate, rapid estimation of weight in the acute care rapid estimation of weight in the acute care setting—e.g., use in emergency setting or setting—e.g., use in emergency setting or resource poor countries for quick dosing resource poor countries for quick dosing calculationscalculations

Study population: 625 children 2months to 16 Study population: 625 children 2months to 16 years old enrolled into 17 strata years old enrolled into 17 strata

Protocol Final and target first enrollment Protocol Final and target first enrollment January 2012January 2012

Other Task OrdersOther Task Orders

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MidazolamMidazolam Analysis of previously collected dataAnalysis of previously collected data

Provide supplemental data to support of the current Provide supplemental data to support of the current prescription labeling to include the treatment of seizuresprescription labeling to include the treatment of seizures

AmpicillinAmpicillin Original written request, PK study and efficacy study in Original written request, PK study and efficacy study in

infantsinfants

PPRU (Pediatric Pharmacology Research Unit) collected PPRU (Pediatric Pharmacology Research Unit) collected samplessamples

ObesityObesity Analysis to provide preliminary data and hand held Analysis to provide preliminary data and hand held

application for dosing in obese childrenapplication for dosing in obese children

Lessons Learned Main Contract TimelinesLessons Learned Main Contract Timelines

Meropenem RFP NIH-NICHD-2005-18 released August Meropenem RFP NIH-NICHD-2005-18 released August 2005, submitted October 20052005, submitted October 2005

Signed September 2007 (24 months)Signed September 2007 (24 months)

Protocol in written as part of application; IND granted Protocol in written as part of application; IND granted March 2008 (31 months)March 2008 (31 months)

Site contracts, IRB, investigators meetingSite contracts, IRB, investigators meeting

First patient June 2008First patient June 2008

200 infants; last infant enrolled September 2009200 infants; last infant enrolled September 2009

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Lessons Learned Main Contract TimelinesLessons Learned Main Contract Timelines

Meropenem RFP release to Meropenem RFP release to signature 24 monthssignature 24 months

IND 31 monthsIND 31 months

First patient 34 monthsFirst patient 34 months

Last infant 48 monthsLast infant 48 months

Clinical Study Report 60 Clinical Study Report 60 months from RFP releasemonths from RFP release

Pediatric Trials Network RFP Pediatric Trials Network RFP 3/2010, signature 6 months 3/2010, signature 6 months

IND 7 monthsIND 7 months

First patient 9 monthsFirst patient 9 months

Last patient 18 monthsLast patient 18 months

Clinical study report 22 Clinical study report 22 months (anticipated)months (anticipated)

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Differences in timelinesDifferences in timelines

IRB vs. ContractsIRB vs. Contracts

Single entity of PTN mitigatesSingle entity of PTN mitigates Risk to NIHRisk to NIH Risk to investigatorsRisk to investigators

Contracts with sitesContracts with sites Opportunistic studyOpportunistic study

Contracts with vendorsContracts with vendors

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Comparison of output and efficiencyComparison of output and efficiency

Legacy Trials vs PTNLegacy Trials vs PTN

Legacy Trials Timeline Legacy Trials Timeline 8 years8 years

PTN 12–18 monthsPTN 12–18 months

Similar number of patientsSimilar number of patients

PTN more INDsPTN more INDs

By 24 months: studies By 24 months: studies enrolling more patients, in enrolling more patients, in more sites, under more more sites, under more INDsINDs

Detailed ComparisonDetailed Comparison

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Pricing differentialPricing differential

Per patient pricing reduced 30–50%Per patient pricing reduced 30–50%

Faculty (thought leadership)Faculty (thought leadership) Winning a grant, conduct of the grantWinning a grant, conduct of the grant Junior facultyJunior faculty K23 awardees and young investigatorsK23 awardees and young investigators

Operations (staff) efficiencyOperations (staff) efficiency

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Pediatric Trials Network (PTN) 2012 tentativePediatric Trials Network (PTN) 2012 tentative

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How Do I Participate in the PTN? How Do I Participate in the PTN?

The POPS study: The POPS study: children interact with the health care system children interact with the health care system

(e.g., admitted to the PICU or seen in the ER)(e.g., admitted to the PICU or seen in the ER) on a prioritized off-patent therapeutic that has on a prioritized off-patent therapeutic that has

insufficient dosing information in their clinical insufficient dosing information in their clinical stratumstratum

age-based: e.g., premature neonatesage-based: e.g., premature neonatesacuity based: e.g., resuscitation medsacuity based: e.g., resuscitation medsclinical-based: e.g., ethnicity, obesityclinical-based: e.g., ethnicity, obesity

ask for consent to take blood at pre-specified ask for consent to take blood at pre-specified times based on dosing interval (Q4 vs. Q24)times based on dosing interval (Q4 vs. Q24)

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PTN and POPS ContinuedPTN and POPS Continued

15 or more therapeutics bundled into one protocol15 or more therapeutics bundled into one protocol

Samples stored locally and sent in batchSamples stored locally and sent in batch

Flexibility to add moleculesFlexibility to add molecules

Provide preliminary and supportive data for Provide preliminary and supportive data for subsequent trials subsequent trials Compare to epi-dataCompare to epi-data Metronidazole exampleMetronidazole example

Provide a testing ground for sites—enrollmentProvide a testing ground for sites—enrollment

Facilitate contracts and infrastructure—enrollment Facilitate contracts and infrastructure—enrollment in between more traditional trialsin between more traditional trials

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Contacting the PTN for the POPS trialContacting the PTN for the POPS trial

POPS Protocol Chair: Micky Cohen-Wolkowiez POPS Protocol Chair: Micky Cohen-Wolkowiez michael.cohenwolkowiez@duke.edu

POPS project lead: Barrie Harper POPS project lead: Barrie Harper barrie.harper@duke.edu

www.pediatrictrials.org

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Limits of the mechanismLimits of the mechanism

OpportunisticOpportunistic

PK and PK-PDPK and PK-PD

SafetySafety

EfficacyEfficacy

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