Phase I/II, Open-Label, Pharmacokinetic and Safety Study of a Novel Protease Inhibitor (BMS 232632, Atazanavir, ATV, Reyataz) in Combination Regimens in Antiretroviral Therapy (ART)-Naive and -Experienced HIV-Infected Infants, Children, and Adolescents

NCT00006604 Phase 1/Phase 2 COMPLETED Results posted

The purpose of this study was to find a safe and tolerable dose of the protease inhibitor (PI) atazanavir (ATV), with or without a low-dose boost of the PI ritonavir (RTV), when taken with other anti-HIV drugs in HIV infected infants, children, and adolescents. Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make, in part because these patients often do not take the drugs as prescribed. ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly. Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment (HAART)-experienced patients. This study aimed to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants, children, and adolescents. For this study, participants were enrolled in the United States and South Africa.

Details

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1/Phase 2
Status	COMPLETED
Enrolment	195
Start date	2000-11
Completion	2014-09

Conditions

• HIV Infections

Interventions

• ATV
• Ritonavir

Primary outcomes

• Number of Participants Who Experienced a Safety Endpoint of Interest Attributed to ATV — From study entry up to week 96
  Total Bilirubin \>= 5.1xULN, ECG Events and Other Grade 3+ toxicities attributed to study treatment. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) Toxicity Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the study team.
• Number of Participants Who Died — From study entry up to week 96
• Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC24h) — Week 1 (Day 7) Intensive PK-24hr (Pre-Dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose)
  Pharmacokinetics were determined by non-compartmental analysis and AUC0-24hr calculated by the linear trapezoidal method.
• Pharmacokinetic (PK) Parameter: Minimum Plasma Concentration (C24) — Week 1 (Day 7) Intensive PK-24hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose)
  Pharmacokinetics were determined by non-compartmental analysis. C24 determined visually, except in the instance when the patient re-dosed the study medication prior to the 24 hour blood draw or the 24 hour level was not obtained, in which case the C24 was calculated from the elimination rate (ke) and the last measured concentration.
• Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) — Week 1 (Day 7) Intensive PK-24 hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose)
  Pharmacokinetics were determined by non-compartmental analysis and Maximum concentration (Cmax) was determined visually.
• Pharmacokinetic (PK) Parameter: Clearance (CL/F) — Week 1 (Day 7) Intensive PK-24 hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose)
  Pharmacokinetics were determined by non-compartmental analysis and Apparent oral clearance (CL/F) was calculated as ATV dose divided by AUC0-24hr.

Countries

United States, Puerto Rico, South Africa