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Pediatric Clinical Trials at the National Institutes
of Health
Anne Zajicek, MD, PharmDObstetric and Pediatric Pharmacology
BranchCenter for Research for Mothers and
ChildrenNational Institute of Child Health and Human
Development, NIH
Outline
ClinicalTrials.gov listings Pediatric Clinical Trials in the Obstetric and
Pediatric Pharmacology Branch Pediatric Pharmacology Research Units Network Best Pharmaceuticals for Children Act Grants
ClinicalTrials.gov
Industry: 5250 total studies (adults + children), 813 enrolling children (15 %)
Other Federal Agencies: 627 total studies, 151 in children (24 %)
NIH: 4892 total studies, 1400 in children
(29 %)
Pediatric Clinical Trials: ongoing/all trials including closed Sponsor
PhaseNIH Other Fed FDA Industry Univ/Org
I172/681 14/38 6/12 62/179 286/604
II342/1311 27/57 18/27 209/606 591/1311
III210/637 23/61 6/14 342/1043 406/896
IV36/96 12/35 1/1 169/381 238/447
I - IV685/2548 69/167 26/45 721/2066 1342/2908
All1400/4892 151/356 41/82 813/2341 2391/4610
Break-down by InstituteInstitute Total Trials In children
NCI 1669 414
NHLBI 322 120
NIAID 395 188
NICHD 244 175
NIDDK 270 101
NIMH 367 111
NINDS 240 65
NIDA 229 43
ORD 19 12
Obstetric Pharmacology Research Units
Funded in 2004 Define pharmacokinetic (PK),
pharmacodynamic (PD), pharmacogenomic (PG) changes that occur during pregnancy Opportunistic PK studies PK studies of 17α hydroxyprogesterone caproate
used to prevent of preterm delivery PK/PD/PG studies in glyburide
Pediatric Pharmacology Research Units
First funded in 1994 Purpose: to improve knowledge of PK, PD,
PG in children 13 sites Performs Phase 1, 2, 3 studies in children of
all ages
NIH Rapid Access to Interventional Development (RAID)
Purpose: to make available, on a competitive basis, certain critical resources needed for the development of new small molecule therapeutic agents
Projects associated with NICHD Metastin Friedrich ataxia
More funding available than projects- please apply Contact information
(301) 594-4660 [email protected]
Best Pharmaceuticals for Children Act
Legislation signed into law 2002, sunsets Oct 2007
Purpose: improve pediatric labeling Extends marketing exclusivity for on-patent
drugs if FDA-requested studies (as described in the Written Request) are performed
For off-patent drugs: NIH prioritizes drugs for study, sponsors clinical trials if the Written Request declined
Master List of all Off-Patent Drugs which lack adequate pediatric labeling
N=200
Consultation with experts in pediatric practice and research
Develop, prioritize, publish an Annual List
N=5-15
Consider for prioritizing: Availability of S/E dataAre additional data needed?Will new studies produce health benefits?Reformulation?
Drugs on the Priority List: January 2003
FR 68: 13; Jan 21, 2003
Azithromycin
Baclofen Bumetanide Dobutamine Dopamine Furosemide Heparin
Lithium
Lorazepam Rifampin Sodium nitroprusside Spironolactone
Drugs on the Priority List: August 2003
FR 68: 156; Aug 13, 2003
Ampicillin/sulbactam Diazoxide
Isoflurane Lindane Meropenem
Metoclopramide Piperacillin/
tazobactam Promethazine
Drugs on the Priority List: February 2004
FR 69:30; February 13, 2004
AmpicillinKetamine Vincristine Dactinomycin Metolazone
Drugs on the Priority List: January 2005
FR 70:17; January 27, 2005
Ivermectin Hydrocortisone valerate Hydrochlorothiazide Ethambutol Griseofulvin Methadone Hydroxychloroquine Sevelamer Morphine
Drugs on the Priority List: January 2006 FR 71:79; April 25, 2006
Sickle Cell Disease: Hydroxyurea Oncology: Methotrexate, Daunomycin Poisoning: Pralidoxime Other disease areas of continuing
interest/discussion: ADHD Hypertension Parasitic Diseases Influenza
Off-Patent Written Requests Issued by FDA Lindane Rifampin
Methicillin resistant Staph aureus endocarditis CNS shunt infections
Meropenem Vincristine Actinomycin-D Ampicillin Griseofulvin Methotrexate
Off-Patent Written Requests Issued by FDA
Lorazepam Sedation Status epilepticus
Nitroprusside Azithromycin
for Ureaplasma pneumonia Azithromycin for Chlamydia
Baclofen* Lithium Morphine* Hydroxyurea*
Off-Patent Written Requests Declined by Industry
Rifampin MRSA endocarditis CNS shunt infections
Meropenem Vincristine Dactinomycin Ampicillin Griseofulvin Methotrexate
Off-Patent Written Requests Declined by Industry
Lorazepam Sedation Status epilepticus
Nitroprusside Azithromycin
for Ureaplasma pneumonia Azithromycin for Chlamydia
Baclofen* Lithium Morphine*
On-Patent Written Requests Declined by Industry
Morphine* Bupropion Sevelamer Zonisamide Hydroxyurea Baclofen* Dexrazoxane Eletriptan Metoclopramide*
Pediatric Studies that are on-going under BPCA
Contracts
Contracts awarded Lorazepam for sedation
Is lorazepam more effective than midazolam? How should lorazepam be given, by intermittent bolus
or by continuous infusion? Lorazepam for status epilepticus
What is the correct dose of lorazepam to treat seizures?
Is lorazepam more effective or safer than diazepam for children in status epilepticus?
BPCA Studies on-going
Nitroprusside for controlled hypotension What is the dose-response relationship for nitroprusside? Is there tolerance to the hypotensive effect?
Ketamine (pre-clinical) Does ketamine cause apoptosis?
Lithium for acute mania Is lithium safe and effective for the treatment of acute
mania in children with bipolar disease? Baclofen for spasticity in cerebral palsy
Is oral baclofen safe and effective in children with cerebral palsy?
BPCA Studies On-going
Methylphenidate Replication of cytogenetic studies in children
receiving methylphenidate
Intra-Agency Agreements Vincristine Actinomycin-D
What is the incidence of toxicity in children? What are the toxicities, and is there a relationship to dose,
diagnosis, age, weight? Is there a relationship between systemic exposure and
efficacy/toxicity?
Methotrexate and neurocognition Is the method of dosing MTX related to neurocognitive
changes in children with high-risk acute lymphocytic leukemia?
Daunomycin: relationship of disposition to body size Hydroxyurea in sickle-cell disease
Contracts under Negotiation
Meropenem for complicated intra-abdominal infections
Grant
Morphine To evaluate the relationship of developmental
stage (defined by both gestational and postnatal age) to the disposition of morphine and the clinical response
Coordinating Center
Purpose: Coordinate patient enrollment Coordinate, monitor data collection Report adverse events and other data (usually blinded) to
Data Safety Monitoring Board (DSMB) Analyze, organize results into a supplemental NDA for
submission to FDA
Contract awarded to Premier Research, Philadelphia, Pennsylvania
Summary
NIH is sponsoring clinical studies in children that will produce improvements in pediatric therapeutics