PENTA15: Pharmacokinetic Study of Once Versus Twice Daily Abacavir in HIV-1 Infected Children Aged 3 to <36 Months (PENTA15)

PENTA15: Plasma Pharmacokinetic Study of Once Versus Twice Daily Abacavir as Part of Combination Antiretroviral Therapy in Children With HIV-1 Infection Aged 3 Months to <36 Months

To compare the plasma pharmacokinetic (PK) parameters of q24h versus q12h dosing of abacavir in HIV-1-infected infants and children aged 3 months to 36 months

The secondary objectives of PENTA15 were:

To compare the plasma PK parameters of q24h versus q12h dosing of lamivudine in HIV-1-infected infants and children aged 3 months to 36 months who were receiving lamivudine in combination with abacavir

To compare age-related differences in the PK parameters of q24h versus q12h dosing of abacavir and lamivudine infants and children in 3 age groups (≥3 to <12 months, ≥12 to <24 months and ≥24 to <36 months)

To describe child and family acceptability of and adherence to q24h compared to q12h dosage regimens of abacavir and lamivudine

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Other: Intervention 1: PK assessment while on Twice Daily Abacavir; Other: Intervention 2: PK assessment while on Once Daily Abacavir

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Hôpital Port Royal
  • Paris, France
    • Hopital Robert Debre
• Germany
  • Munich, Germany
    • Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
• Italy
  • Padova, Italy, 35128
    • Clinica Pediatrica, Università di Padova
• Spain
  • Getafe, Spain
    • Hospital Universitario
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Hospital Gregorio Marañón
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital
  • London, United Kingdom
    • Evelina Children's Hospital
  • London, United Kingdom
    • St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants and children with confirmed presence of HIV-1 infection
• Infants and children aged 3 to <36 months
• Parents/guardians able and willing to give written, informed consent
• Currently on combination ART including Abacavir (ABC) oral solution with or without Lamivudine (3TC) oral solution, for at least 12 weeks and expected to stay on this regimen for at least a further 12 weeks.

• HIV-1 RNA viral load either;

  • suppressed HIV-1 RNA viral load (i.e. <400 copies/ml)
  • non-suppressed, but low, HIV-1 RNA viral load (i.e. 400-20 000 copies/ml). The non-suppressed children should have had a stable or decreasing HIV-1 RNA viral load prior to study entry and should be considered to be still gaining benefit from the current regimen
• Stable or rising CD4+ cell percent prior to study entry and should not be expected to fall within the next 12 weeks.

Exclusion Criteria:

• Intercurrent illness
• Receiving concomitant therapy except prophylactic antibiotics
• Abnormal renal or liver function (grade 3 or above)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Abacavir Once versus Twice Daily; This is a single arm study. Intervention 1: PK assessment while on Twice Daily Abacavir (Week 0) Intervention 2: PK assessment while on Once Daily Abacavir (Week 4)	Other: Intervention 1: PK assessment while on Twice Daily Abacavir; Week 0; Other Names: Ziagen; ABC; Other: Intervention 2: PK assessment while on Once Daily Abacavir; Week 4; Other Names: Ziagen; ABC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC) (0-24) of Abacavir on Twice Daily Dosing	Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication.	Week 0
Cmax of Abacavir on Twice Daily Dosing	Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours post-ingestion of medication.	Week 0
AUC(0-24) of Abacavir on Once Daily Dosing	Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication	Week 4
Cmax of Abacavir on Once Daily Dosing	Blood samples were taken at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 12 and 24 hours post-ingestion of medication.	Week 4

Collaborators and Investigators

• Sponsor: PENTA Foundation

Publications and helpful links

General Publications

• Paediatric European Network for Treatment of AIDS (PENTA). Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months. Antivir Ther. 2010;15(3):297-305. doi: 10.3851/IMP1532.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 25, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Estimate): March 20, 2014
• Last Update Submitted That Met QC Criteria: February 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: HIV; Lamivudine; Pharmacokinetics; Abacavir
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Abacavir; Dideoxynucleosides
• Other Study ID Numbers: PENTA15; 2005-004433-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No