Transcript 2014 03 27 PTN slides for FDA

PEDIATRIC TRIALS
NETWORK
March 27, 2014
A project of the Best Pharmaceuticals for Children Act
Why are studies in children difficult?
• Limited number of patients with the disease
• No “healthy child/baby volunteer”
• Low rates of parental informed consent
• Perceived study risks
• Limited blood volume and timed sampling
• Sick population – increases variability
• Lack of clinical pharmacology expertise
• Lack of pediatric PK/PD modeling expertise
How Did The PTN Start?
“Create an infrastructure for investigators to conduct
trials that improve pediatric labeling and child health.”
– Sponsored by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD)
– Network for studying drug product formulation, age-appropriate
drug dosing, efficacy, safety, and device validation
– Success: Completed trials that improve dosing, safety
information, labeling, and ultimately child health
Pediatric Trials Network
• PI: Benjamin
• Since 2010, ~25 ongoing projects, 12 clinical trials
• Phase 1 and 2 studies
• All therapeutic areas
• 5 CSRs submitted to FDA
• 4-6 potential label changes
• Training of fellows/junior faculty
PTN Structure
PTN Administrative Core
Name
Role
Center
Daniel Benjamin, MD, Phd
Network PI
Duke University, Durham, NC
Gregory Kearns, Pharm D, PhD
Chair, Clin. Pharmacology Core Children's Mercy Hospital &Clinics, Kansas City, MO
Edmund Capparelli, Pharm D
Chair, Pharmacometrics Core
UC San Diego, San Diego, CA
Andrew Muelenaer, MD
Chair, Devices Core
Virginia Tech Carilion School of Medicine, Roanoke, VA
John van den Anker, MD, PhD
Co-Chair, Mentorship Core
GWU School of medicine & Health Science, Washington, DC
Kelly Wade, MD, PhD
Co-Chair, Safety & Ethics Core Children's Hospital of Philadelphia, Philadelphia, PA
Michael O'Shea, MD
Co-Chair Devices Core
Wake Forest University Medical Center, Winston-Salem, NC
P. Brian Smith, MD
Network Co-Investigator
Duke University, Durham, NC
Michael Cohen-Wolkoweiz, MD, PhD Network Co-Investigator
Duke University, Durham, NC
Matthew Laughon, MD
Administrative Core
UNC Memorial Hospital, Chapel Hill, NC
Ian Paul, MD
Administrative Core
Penn State College of Medicine, Hershey, PA
Anne Zajicek, MD, PharmD
Branch Chief
NIH/NICHD, Bethesda, MD
David Siegel, MD
NICHD COTR
NIH/NICHD, Bethesda, MD
Perdita Taylor-Zapata, MD
NICHD COTR
NIH/NICHD, Bethesda, MD
Ravinder Anand, PhD
DCC PI
The Emmes Corporation, Rockville, MD
Traci Clemons, PhD
DCC Co-PI
The Emmes Corporation, Rockville, MD
PTN Fellows
Fellow
Specialty
TO#
Skill (PK/operations)
Daniela Testoni
Neonatology
fluconazole, Pediatrix, POPS
Operations/PK
Julie Autmizguine
ID
SCAMP, staph-trio, POPS
Operations/PK
Daniel Gonzalez
Pharmacology
lorazepam, staph-trio
Operations/PK
Lawrence Ku
Neonatology
bpd, SCAMP
Operations/PK
Susi Hupp
Critical Care
methadone
Operations
Jessica Erickson
ID
clinda obesity
Operations
Yamini Virkud
Allergy
sildenafil
Operations
Kanecia Zimmerman
Critical Care
pantoprazole, POPS
Operations
Christoph Hornik
Cardiology
Pediatrix, ampicillin, obesity database Biostatistics, Operations
Mario Sampson
Pharmacology
metronidazole, acyclovir
Operations/PK
Margreet Van Ginkel
Clinical Research
obesity database
Operations
Kristian Becker
Clinical Research
obesity database
Operations
Pediatric Trials Network
PTN Site Participation
• 255 investigators at 138 sites expressed interest in
participating
• Anticipate ~60 sites actively enrolling in trials conducted in
2014
• Growth of the “rapid start network”, a pediatric clinical trial
consortium affiliated with PTN to a total of approximately
100 sites
PTN Update
•
Metronidazole: 3 sites, 24 premature infants at risk for NEC. Protocol chair: Michael
Cohen-Wolkowiez. Enrollment and analysis complete, CSR submitted to FDA, published in
PIDJ
•
Acyclovir: 3 sites, 32 preterm and term infants with suspected HSV. Protocol chair: Brian
Smith. Enrollment and analysis complete, CSR submitted to FDA, published in PIDJ
•
TAPE weight estimate device: 3 sites, 625 children. Protocol chair: Sue Rahman,
Children’s Mercy Hospital, Kansas City, MO. Enrollment and analysis complete. CSR
submitted to FDA, published Ann of Emer Med
•
Hydroxyurea: 6 sites, 40 children. Protocol chair: Kathleen Neville, Children’s Mercy
Hospital, Kansas City, MO. Enrollment and analysis complete. CSR submitted to FDA
•
Opportunistic (POPS I and POPD II): 36sites, 1200 children. Protocol chair: Michael
Cohen-Wolkowiez. Enrollment ongoing (>1000 enrolled to date)
•
Lisinopril PK: 8 sites, 24 children with kidney transplants and HTN. Protocol chair: Howard
Trachtman, NYU Langone Medical Center. Enrollment complete. Analysis ongoing
PTN Update
•
Midazolam meta-analysis: Support change of current midazolam labeling to include the
treatment of seizures in children ages 2 years and older using existing PK and safety data.
Protocol chair: Brian Smith. Analysis in progress.
•
Ampicillin meta-analysis: PK analysis in combination with 2 retrospective cohort studies of
infants with sepsis and/or meningitis. 1 site, 64 infants. Protocol chair: Michael CohenWolkowiez. Data collection and analysis complete, CSR submitted to FDA. PAS poster.
•
Obesity informatics: Literature search to create a database with published PK studies for
the NIH Priority Drug List relevant to pediatric obesity. Protocol chair: Kevin Watt.
Literature review complete. PAS poster.
•
Staph microtrials: 9 sites, 96 infants, 3 anti-staph drugs. Protocol chair: Matt Laughon,
UNC. Enrollment ongoing.
•
Sildenafil: 5 sites, up to 24 infants with pulmonary arterial hypertension or lung disease.
Protocol chair: Matt Laughon, UNC. Enrollment ongoing.
•
Clindamycin obesity: 6 sites, up to 32 children. Safety/PK study of multiple-dose IV and
oral clindamycin in obese children. Protocol chair: Janice Sullivan, University of Louisville,
KY. Enrollment ongoing. Federated IRB.
PTN Update
•
Methadone PICU: 4 sites, up to 36 patients. Protocol chair: Kevin Watt. Enrollment
ongoing.
•
Diuretics in NICU: retrospective review: 2 sites, 700 pts. Protocol Chair: Matt
Laughon, UNC. Data collection ongoing.
•
Piperacillin-tazobactam, clindamycin, metronidazole, ampicillin safety in infants with
complicated intraabdominal infections (SCAMP): 50 sites, 374 subjects, Protocol
Chair: Michael Cohen-Wolkowiez. Site start up
•
Pantoprazole obesity: 3 sites and 60 children. Study to determine effect of obesity on
the PK/PD of pantoprazole in children. Protocol chair: Greg Kearns, Children’s Mercy
Hospital, Kansas City, MO. Site start up.
•
Pediatrix meta-analysis of safety of 11 drugs: Retrospective data analysis; database
to include >300 sites and >800,000 infants and data from FDA. Protocol chair: Brian
Smith. Data analysis.
•
Fluconazole safety meta-analysis: 33 sites, 361 infants enrolled in an earlier RCT.
Protocol chair: Brian Smith. Data analysis.
PTN Resources
• How to get involved:
https://pediatrictrials.org/how-to-get-involved
• How to develop a concept sheet:
https://pediatrictrials.org/how-to-get-involved/forhealthcare-professionals