Once daily regimen of ftc ddi efv in arv therapy na ve children
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Once-Daily Regimen of FTC, DDI, EFV in ARV Therapy-Naïve Children. PACTG 1021. Organization. Pediatric AIDS Clinical Trials Group NIAID and NICHD sponsored Drug and expertise provided by: Triangle Pharmaceuticals – Gilead Sciences Bristol Myers Squibb. Justification.

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Presentation Transcript

Organization
Organization Children

  • Pediatric AIDS Clinical Trials Group

    • NIAID and NICHD sponsored

  • Drug and expertise provided by:

    • Triangle Pharmaceuticals – Gilead Sciences

    • Bristol Myers Squibb


Justification
Justification Children

  • Once a day regimen improves compliance

  • Long half-life drugs might be more forgiving

  • Side effect profiles for all three drugs (FTC, ddI, EFV) individually are manageable


Patient population
Patient Population Children

  • ARV Naïve (allowed perinatal prophylaxis)

  • Three cohorts, n=37:

    • 90 days to <3 years (not reported at this meeting – currently enrolling)

    • 3 years to 12 years [21 subjects]

    • 13 years to 21 years [16 volunteers]

  • Enrollment between 9/18/2001 and 10/23/2002

  • Data cut off – August 2, 2004



Regimen once daily
Regimen (Once Daily) Children

  • FTC 6 mg/kg (maximum 200 mg)

  • ddI 240 mg/m2 (maximum 400 mg)

    • Oral suspension or ddI enteric coated beadlet capsules

  • Efavirenz – Dosing Table

    • Oral solution (30 mg/ml)

    • Capsules (50/100/200 mg)


Study design
Study Design Children

  • Open label, Phase I-II

  • Every 4 week visits through week 96

  • Intense PK at weeks 2, 8/12, and time of discontinuation

  • Multiple spot levels drawn

  • Intention to Treat Analysis

  • Endpoints: Safety, tolerance, proportion <50 HIV copies/ml; <400 HIV copies/ml


Pk result
PK Result Children

  • FTC and ddI pharmacokinetics provided anticipated AUCs

  • EFZ – Initial levels below anticipated for children ≤12 years receiving oral solution, so dose increased

    • Median AUCs (prior to adjustment)


Adverse events
Adverse Events Children

  • 2 children discontinued before 2 weeks due to rash (one Grade 3, one Grade 2)

  • No subjects with laboratory abnormalities attributed to drug regimen

    • 1 Grade 4 hypoglycemia, 2 grade 3 CPK considered “possibly” related

  • 2 subjects had Grade 3 symptoms attributed to the regimen (rash; dizziness [wk1 – resolved spontaneously])


Viral response
Viral Response Children




Discontinuations
Discontinuations Children

  • 10/37 Subjects discontinued treatment

    • 2 Rashes

    • 3 Virologic failure

    • 2 Adolescents incarcerated

    • 2 Subjects felt visits were inconvenient

    • 1 Subject moved out of the country

  • No Deaths or new Category C diagnoses


Conclusions
Conclusions Children

  • Once daily Combination of FTC/ddI/EFZ well tolerated – 2 subjects with rash

  • Efficacy appeared to be good:

    • Using ITT, 72% <50 copies at week 96

    • Only 3/37 discontinued because of viral failure

  • CD4 response was very positive: median CD4 % went from 17% to 32%


Acknowledgement
Acknowledgement Children

  • Thank you to study volunteers and their families

  • Thank you to clinic staff of the 16 sites


Pactg 1021 study team

Ross E. McKinney, Jr, M.D. Children

Mobeen Rathore, M.D.

Chengcheng Hu, Ph.D.

Paula Britto, M.S.

Michael Hughes, Ph.D.

Mary Elizabeth Smith, M.D.

Leslie K. Serchuk, M.D.

Joyce Kraimer, M.S.

Alberto A. Ortiz, M.S.

Linda Draper

Paul Tran, R.Ph.

Patricia Flynn, M.D.

Ram Yogev, M.D.

Stephen Spector, M.D

Coleen Cunningham, M.D.

Elaine Abrams, M.D.

Melissa Scites, R.N.

Ruth Dickover, Ph.D.

Adrianna Weinberg, M.D.

John Rodman, Pharm.D.

H. Robert Blum, Ph.D.

Gregory E. Chittick

Laurie Reynolds

PACTG 1021 Study Team


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