IMPAACT P1066: Raltegravir (RAL) safety and efficacy in treatment experienced HIV infected (+) youth 2 to 18 years of age through week 48 S. Nachman 1 , E. Acosta 2 , N. Zheng 3 , H. Teppler 4 , B. Homony 4 , X. Xu 4 , C. Alvero 3 , E. Handelsman 5 , C. Worrell 6 , B. Graham 7 , M. Toye 8 , A. Wiznia 9 , and the P1066 Group 4th International Workshop on HIV Pediatrics Washington DC, USA, 20-21 July 2012 1 SUNY Stony Brook, Pediatrics, Stony Brook, United States; 2 University of Alabama at Birmingham, Birmingham, United States; 3 Harvard School of Public Health, Boston, United States; 4 Merck, North Wales, United States; 5 Division of AIDS, NIAID, NIH, Bethesda, United States; 6 Natl Inst of Child Hlth and Human Devt, Bethesda, United States; 7 Frontier Science Inc, Buffalo, United States; 8 Baystate Medical Center, Springfield, United States; 9 Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, United States
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IMPAACT P1066: Raltegravir (RAL) safety and efficacy in treatment experienced
HIV infected (+) youth 2 to 18 years of age through week 48
S. Nachman1, E. Acosta2, N. Zheng3, H. Teppler4, B. Homony4, X. Xu4, C. Alvero3, E. Handelsman5, C. Worrell6, B. Graham7,
M. Toye8, A. Wiznia9, and the P1066 Group
4th International Workshop on HIV Pediatrics Washington DC, USA, 20-21 July 2012
1SUNY Stony Brook, Pediatrics, Stony Brook, United States; 2University of Alabama at Birmingham, Birmingham, United States;
3Harvard School of Public Health, Boston, United States; 4Merck, North Wales, United States;
5Division of AIDS, NIAID, NIH, Bethesda, United States; 6Natl Inst of Child Hlth and Human Devt, Bethesda, United States;
7Frontier Science Inc, Buffalo, United States; 8Baystate Medical Center, Springfield, United States;
9Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, United States
Background
New antiretrovirals are needed for HIV+ children.
IMPAACT P1066 is an international Phase I/II open label multicenter trial to evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of multiple RAL formulations in treatment experienced HIV+ youth
Study Design (1) Open label, multi-center study conducted in US, South
Africa, Botswana, Brazil, Argentina Population: HIV+ youth who failed ≥ one ART regimen
with HIV RNA >1000 < 2yrs may have failed only PMTCT
2-stage study: Stage 1 performed intensive PK for dose
finding/safety Stage 2 enrolled additional patients at selected (final)
dose Dose selection based on intensive PK and safety data:
RAL film-coated (adult) tabs: 400 mg BID for 6-18 yrs and ≥ 25kg RAL chewable: weight-based dosing at ~6mg/kg (75-300mg)
BID for 2 -<12 yrs RAL oral granules for suspension (< 2yrs) ongoing
RAL was given with an optimized background regimen Subjects were enrolled sequentially in 5 age cohorts
Study Design (2) Formulation Summary
Cohort Age Formulation I 12-18 yrs Adult
IIA 6-11 yrs Adult IIB 6-11 yrs Chewable III 2-5 yrs Chewable IV 6mos – 2 yrs Granules for Susp V 4wks – 6mos Granules for Susp
Chewables available in 25 mg and 100 mg (scored), orange banana flavor Granules in sachets of 100 mg, reconstitute in 5mL water, banana flavor
Study Design (3) Endpoints: Safety: Grade 3+ or serious adverse events (AE) Efficacy:
Primary: vRNA < 400c/mL or ≥1 log reduction Secondary: vRNA < 50c/mL, change in CD4 count (%) Used Observed Failure missing data approach
Time points: Primary: 24 wk Secondary: 48 wk
Analysis Populations: Primary : subjects who received only the final selected dose ITT population: all treated subjects
Here we present demographics and 48 week safety and
efficacy data in 96 subjects 2-18yr (Cohorts I-III) who received RAL only at the final selected dose
Recommended Dose for Raltegravir (ISENTRESS) Chewable Tablets in Pediatric Patients 2 to Less Than 12 Years of Age –
From US Product Circular Body weight (kg) Dose Number of Chewable
tablets 10 to <14 kg 75 mg twice daily 3 x 25 mg twice daily 14 to <20 kg 100 mg twice daily 1 x 100 mg twice daily 20 to <28 kg 150 mg twice daily 1.5 x 100* mg twice
daily 28 to < 40 kg 200 mg twice daily 2 x 100 mg twice daily At least 40 kg 300 mg twice daily 3 x 100 twice daily
• The weight based dosing recommendation for the chewable tables is based on approximately 6 mg/kg/dose twice daily
• *The 100 mg chewable tablet is scored and can be divided into equal halves
The study team would like to thank the sponsors, sites and families who
participated in this study NIAID: Ed Handelsman NICHD: Carol Worrell Merck: Hedy Teppler Merck: Brenda Homony Merck: Xia Xu Merck: Matthew Rizk Merck: Larissa Wenning Merck: Elizabeth Rhee SDAC: Terrence Fenton SDAC: Nan Zheng SDAC: Carmelita Alvero SSS: Kim Hudgens and
Liz Petzold
FSTRF: Bobbie Graham Pharmacist: Lynette Purdue Pharmacologist: Edward Acosta Virologist: Lisa Frenkel Immunologist: Steve Douglas Lab Technologist: Nancy Tustin Lab Manager: Carrie Fry Investigators: Steve Spector