Transcript PTN overview 2011-2012

Pediatric Trials Network
What Is The Pediatric Trials Network PTN?

Sponsored by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD)
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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
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Evidence of success will be completed trials that improve dosing,
safety information, labeling, and ultimately child health
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Structure of PTN
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Pediatric Trials Network (PTN) 2011
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Protocol: Metronidazole
Protocol Chair: Cohen-Wolkowiez
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Protocol Title: Safety and Pharmacokinetics of Multiple Dose
Metronidazole in Premature Infants
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Objective: Evaluate the safety, PK, and surrogate PD of
intravenous metronidazole in premature infants with
suspected serious infection
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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.
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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.
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Number of Sites: 3
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October, 2011 Enrollment Complete
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Demographic Distribution:
These data have not been peer-reviewed
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Metronidazole Individual EBE PK Parameter Estimates by
Post Natal Age Group:
These data have not been peer-reviewed
Group
<14
≥14
N
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CL (L/kg/h)
0.028 (0.018, 0.059)
0.039 (0.017, 0.125)
V (L/kg)
0.96 (0.83, 1.01)
0.96 (0.89, 1.05)
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Concentration vs. Time:
These data have not been peer-reviewed
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Clearance vs. Post Menstrual Age:
These data have not been peer-reviewed
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Protocol: Acyclovir
Protocol Chair: Smith
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Protocol Title: An Open Label Study to Describe the
Pharmacokinetics of Acyclovir in Premature Infants
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Objective: To evaluate the safety and PK of IV acyclovir in
premature infants with suspected systemic infections.
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Study Population: 20 Infants < 45 days postnatal age, suspected
to have a systemic infection divided into groups by gestational and
postnatal age
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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
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Number of Sites: 3
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First Patient Enrolled: September 19, 2011; target March 2012
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Protocol: Hydroxyurea
Protocol Chair: Neville
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Protocol Title: PK & Relative Bioavailability of a Liquid Formulation
of Hydroxyurea in Pediatric Patients with Sickle Cell Anemia
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Objective: relative bioavailabilty study and bioequivalence study
with new formulation
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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
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Study duration: a subset of patients in each age cohort will receive
single dose and a subset will receive multiple doses
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Number of Sites: Six
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First Patient: December, 2011
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Protocol: POPS Pediatric Opportunistic PK Study
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Protocol Title: Pharmacokinetics of Understudied Drugs
Administered to Children per Standard of Care
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Objectives:

Evaluate the PK of understudied drugs currently being administered to
children.
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Study Population: 500 children (birth-20 years) who are
receiving understudied drugs of interest per standard of
care as prescribed by their treating caregiver
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Study Duration: each child will participate in the study for
up to 90 days per drug; study conduct for 3 years
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Number of Sites: 15
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First Patient Enrolled: November, 2011
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Protocol: Lisinopril
Protocol Chair: Trachtman
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Protocol Title: Safety and Pharmacokinetics of
Lisinopril in Pediatric Kidney Transplant Recipients
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Objective: initial description of the PK-PD and safety of
lisinopril following transplantation
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Study population: 24 children ages 2-18 with kidney
transplant and stable allograft function
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Study participation: Up to 51 days; enrolled children will
receive multiple doses with multiple assessments for
potential endpoints for subsequent efficacy trial
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Number of Sites: 8
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Target to Enroll First Patient: January 2012
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Protocol: TAPE
Protocol Chair: Rahman
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Protocol Title: Taking the Guesswork out of
Pediatric Weight Estimation (TAPE): Validation
of the Mercy TAPE
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Objective: device trial to provide more accurate,
rapid estimation of weight in the acute care
setting—e.g., use in emergency setting or
resource poor countries for quick dosing
calculations
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Study population: 625 children 2months to 16
years old enrolled into 17 strata
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Protocol Final and target first enrollment
January 2012
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Other Task Orders
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Midazolam
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Analysis of previously collected data
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Provide supplemental data to support of the current
prescription labeling to include the treatment of seizures
Ampicillin
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Original written request, PK study and efficacy study in
infants
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PPRU (Pediatric Pharmacology Research Unit) collected
samples
Obesity
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Analysis to provide preliminary data and hand held
application for dosing in obese children
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Lessons Learned Main Contract Timelines
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Meropenem RFP NIH-NICHD-2005-18 released August
2005, submitted October 2005
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Signed September 2007 (24 months)
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Protocol in written as part of application; IND granted
March 2008 (31 months)
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Site contracts, IRB, investigators meeting
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First patient June 2008
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200 infants; last infant enrolled September 2009
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Lessons Learned Main Contract Timelines
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Meropenem RFP release to
signature 24 months
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Pediatric Trials Network RFP
3/2010, signature 6 months
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IND 31 months
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IND 7 months
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First patient 34 months
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First patient 9 months
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Last infant 48 months
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Last patient 18 months
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Clinical Study Report 60
months from RFP release
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Clinical study report 22
months (anticipated)
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Differences in timelines
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IRB vs. Contracts
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Single entity of PTN mitigates
 Risk to NIH
 Risk to investigators
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Contracts with sites
 Opportunistic study
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Contracts with vendors
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Comparison of output and efficiency
Legacy Trials vs PTN
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Legacy Trials Timeline
8 years
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PTN 12–18 months
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Similar number of patients
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PTN more INDs
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By 24 months: studies
enrolling more patients, in
more sites, under more
INDs
Detailed Comparison
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Pricing differential
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Per patient pricing reduced 30–50%
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Faculty (thought leadership)
 Winning a grant, conduct of the grant
 Junior faculty
 K23 awardees and young investigators
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Operations (staff) efficiency
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Pediatric Trials Network (PTN) 2012 tentative
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How Do I Participate in the PTN?
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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)
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PTN and POPS Continued
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15 or more therapeutics bundled into one protocol
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Samples stored locally and sent in batch
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Flexibility to add molecules
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Provide preliminary and supportive data for
subsequent trials
 Compare to epi-data
 Metronidazole example
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Provide a testing ground for sites—enrollment
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Facilitate contracts and infrastructure—enrollment
in between more traditional trials
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Contacting the PTN for the POPS trial
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POPS Protocol Chair: Micky Cohen-Wolkowiez
[email protected]
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POPS project lead: Barrie Harper
[email protected]
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www.pediatrictrials.org
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Limits of the mechanism
Opportunistic
PK and PK-PD
Safety
Efficacy
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