Pediatric Trials Network

1
Pediatric Trials Network
2
What Is The Pediatric Trials Network PTN?

• Sponsored by the Eunice Kennedy Shriver National
  Institute of Child Health and Human Development
  (NICHD)
• The primary objective of the Pediatric Trials
  Network
• Create an infrastructure for investigators to
  conduct trials that improve pediatric labeling
  and child health.
• PTN is studying product formulation, drug dose,
  efficacy, safety, and device validation
• Evidence of success will be completed trials that
  improve dosing, safety information, labeling, and
  ultimately child health

3
Structure of PTN
4
Pediatric Trials Network (PTN) 2011
5

Protocol Metronidazole Protocol Chair
Cohen-Wolkowiez

• 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 Population16 to 32 participants lt32 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

6
Demographic Distribution These data have not
been peer-reviewed
7
Metronidazole Individual EBE PK Parameter
Estimates by Post Natal Age Group These data
have not been peer-reviewed
8
Concentration vs. Time These data have not
been peer-reviewed
9
Clearance vs. Post Menstrual Age These data
have not been peer-reviewed
10
Protocol Acyclovir Protocol Chair Smith

• Protocol Title An Open Label Study to Describe
  the Pharmacokinetics of Acyclovir in Premature
  Infants
• Objective To evaluate the safety and PK of IV
  acyclovir in premature infants with suspected
  systemic infections.
• Study Population 20 Infants lt 45 days postnatal
  age, suspected to have a systemic infection
  divided into groups by gestational and postnatal
  age
• 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 efficacy
  trial
• Number of Sites 3
• First Patient Enrolled September 19, 2011
  target March 2012

11
Protocol HydroxyureaProtocol Chair Neville

• Protocol Title PK Relative Bioavailability of
  a Liquid Formulation of Hydroxyurea in Pediatric
  Patients with Sickle Cell Anemia
• Objective relative bioavailabilty study and
  bioequivalence study with new formulation
• Study Population 40 children ages 2-17 with
  sickle cell anemia or sickle beta-zero
  thalassemia two-armed study with older children
  (bioequivalence) enrolled first
• Study duration a subset of patients in each age
  cohort will receive single dose and a subset will
  receive multiple doses
• Number of Sites Six
• First Patient December, 2011

12

Protocol POPS Pediatric Opportunistic PK Study

• Protocol Title Pharmacokinetics of Understudied
  Drugs Administered to Children per Standard of
  Care
• Objectives
• Evaluate the PK of understudied drugs currently
  being administered to children.
• Study Population 500 children (birth-20 years)
  who are receiving understudied drugs of interest
  per standard of care as prescribed by their
  treating caregiver
• Study Duration each child will participate in
  the study for up to 90 days per drug study
  conduct for 3 years
• Number of Sites 15
• First Patient Enrolled November, 2011

13
Protocol LisinoprilProtocol Chair Trachtman

• Protocol Title Safety and Pharmacokinetics of
  Lisinopril in Pediatric Kidney Transplant
  Recipients
• Objective initial description of the PK-PD and
  safety of lisinopril following transplantation
• Study population 24 children ages 2-18 with
  kidney transplant and stable allograft function
• Study participation Up to 51 days enrolled
  children will receive multiple doses with
  multiple assessments for potential endpoints for
  subsequent efficacy trial
• Number of Sites 8
• Target to Enroll First Patient January 2012

14
Protocol TAPEProtocol Chair Rahman

• Protocol Title Taking the Guesswork out of
  Pediatric Weight Estimation (TAPE) Validation of
  the Mercy TAPE
• Objective device trial to provide more accurate,
  rapid estimation of weight in the acute care
  settinge.g., use in emergency setting or
  resource poor countries for quick dosing
  calculations
• Study population 625 children 2months to 16
  years old enrolled into 17 strata
• Protocol Final and target first enrollment
  January 2012

15
Other Task Orders

• Midazolam
• Analysis of previously collected data
• Provide supplemental data to support of the
  current prescription labeling to include the
  treatment of seizures
• Ampicillin
• Original written request, PK study and efficacy
  study in infants
• PPRU (Pediatric Pharmacology Research Unit)
  collected samples
• Obesity
• Analysis to provide preliminary data and hand
  held application for dosing in obese children

16
Lessons Learned Main Contract Timelines

• Meropenem RFP NIH-NICHD-2005-18 released August
  2005, submitted October 2005
• Signed September 2007 (24 months)
• Protocol in written as part of application IND
  granted March 2008 (31 months)
• Site contracts, IRB, investigators meeting
• First patient June 2008
• 200 infants last infant enrolled September 2009

17
Lessons Learned Main Contract Timelines

• Meropenem RFP release to signature 24 months
• IND 31 months
• First patient 34 months
• Last infant 48 months
• Clinical Study Report 60 months from RFP release

• Pediatric Trials Network RFP 3/2010, signature 6
  months
• IND 7 months
• First patient 9 months
• Last patient 18 months
• Clinical study report 22 months (anticipated)

18
Differences in timelines

• IRB vs. Contracts
• Single entity of PTN mitigates
• Risk to NIH
• Risk to investigators
• Contracts with sites
• Opportunistic study
• Contracts with vendors

19
Comparison of output and efficiency

• Legacy Trials vs PTN

• Detailed Comparison

• Legacy Trials Timeline 8 years
• PTN 1218 months
• Similar number of patients
• PTN more INDs
• By 24 months studies enrolling more patients, in
  more sites, under more INDs

20
Pricing differential

• Per patient pricing reduced 3050
• Faculty (thought leadership)
• Winning a grant, conduct of the grant
• Junior faculty
• K23 awardees and young investigators
• Operations (staff) efficiency

21
Pediatric Trials Network (PTN) 2012 tentative
22
How Do I Participate in the PTN?

• The POPS study
• children interact with the health care system
  (e.g., admitted to the PICU or seen in the ER)
• on a prioritized off-patent therapeutic that has
  insufficient dosing information in their clinical
  stratum
• age-based e.g., premature neonates
• acuity based e.g., resuscitation meds
• clinical-based e.g., ethnicity, obesity
• ask for consent to take blood at pre-specified
  times based on dosing interval (Q4 vs. Q24)

23
PTN and POPS Continued

• 15 or more therapeutics bundled into one protocol
• Samples stored locally and sent in batch
• Flexibility to add molecules
• Provide preliminary and supportive data for
  subsequent trials
• Compare to epi-data
• Metronidazole example
• Provide a testing ground for sitesenrollment
• Facilitate contracts and infrastructureenrollment
  in between more traditional trials

24
Contacting the PTN for the POPS trial

• POPS Protocol Chair Micky Cohen-Wolkowiez
  michael.cohenwolkowiez_at_duke.edu
• POPS project lead Barrie Harper
  barrie.harper_at_duke.edu
• www.pediatrictrials.org

25
Limits of the mechanism
Opportunistic
PK and PK-PD
Safety
Efficacy
26
(No Transcript)