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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 ) T he primary objective of the Pediatric Trials Network:
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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
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 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
Demographic Distribution: These data have not been peer-reviewed
Metronidazole Individual EBE PK Parameter Estimates by Post Natal Age Group: These data have not been peer-reviewed
Concentration vs. Time: These data have not been peer-reviewed
Clearance vs. Post Menstrual Age: These data have not been peer-reviewed
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 < 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
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
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
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
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 setting—e.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
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
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
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)
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
Comparison of output and efficiency Legacy Trials vs PTN Detailed Comparison • Legacy Trials Timeline 8 years • PTN 12–18 months • Similar number of patients • PTN more INDs • By 24 months: studies enrolling more patients, in more sites, under more INDs
Pricing differential • Per patient pricing reduced 30–50% • Faculty (thought leadership) • Winning a grant, conduct of the grant • Junior faculty • K23 awardees and young investigators • Operations (staff) efficiency
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)
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 sites—enrollment • Facilitate contracts and infrastructure—enrollment in between more traditional trials
Contacting the PTN for the POPS trial • POPS Protocol Chair: Micky Cohen-Wolkowiez michael.cohenwolkowiez@duke.edu • POPS project lead: Barrie Harper barrie.harper@duke.edu • www.pediatrictrials.org
Limits of the mechanism Opportunistic PK and PK-PD Safety Efficacy