Clinical trial NCT00364793: Safety, Tolerability and Pharmacokinetics of Efavirenz in HIV-Infected Children
Official title: An Open-label Study of Liquid and Sprinkled Formulations of Efavirenz Administered in Combination With Didanosine and Emtricitabine in HIV-infected Infants and Children 3 Months to 6 Years of Age.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: HIV, Pediatric
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-08-16
Enrollment: 56
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to find the dose of Efavirenz for young children. The safety and how the medication is tolerated will also be studied.


Eligibility criteria: Inclusion Criteria:

* HIV-1 infected; \>=3 months of age to \<=6 years of age (at time of treatment); screening plasma viral load \>=1000 copies/mL

Exclusion Criteria:

* Genotypic or phenotypic resistance to EFV, ddl, or FTC/lamivudine (3TC) at screening

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: Area Under the Plasma Concentration Time Curve (AUC) Over One Dosing Interval From Time Zero to 24 Hours Post-dose(TAU) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
Secondary outcomes:
measure: The Number of Participants With Plasma HIV RNA < 400 Copies Per Milliliter (c/mL) at Week 48 as Analyzed by Different Algorithms - All Treated Participants
timeFrame: Week 48
measure: The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 48 as Analyzed by Different Algorithms - All Treated Participants
timeFrame: Week 48
measure: The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants
timeFrame: Week 24
measure: The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants
timeFrame: Week 24
measure: Log10 c/mL HIV RNA Changes From Baseline Through Week 48 - Treated Participants
timeFrame: Baseline through Week 48
measure: CD4 Cell Count Change From Baseline at Weeks 24 and 48 - Treated Participants
timeFrame: Baseline to Weeks 24 and 48
measure: Percent of CD4 Cells Change From Baseline at Weeks 24 and 48 - Treated Participants
timeFrame: Baseline to Weeks 24 and 48
measure: Number of Participants With On-Treatment Adverse Events (AEs), Related Adverse Events, Serious Adverse Events (SAEs), Death, Discontinuation Due to Adverse Events, and CDC Class C AIDS Events
timeFrame: Baseline to Week 96
measure: Number of Participants With Liver Function Test Laboratory Abnormalities - Treated Population
timeFrame: Baseline to Week 96
measure: Number of Participants With Lipid and Glucose Laboratory Abnormalities - Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Serum Chemistry Abnormalities - Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Hematologic Abnormalities - Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Treated Participants With Resistance Associated Genotypic and Phenotypic Changes in Viruses - Participants With Virologic Failure, Lack of Suppression or Viral Load Rebound
timeFrame: Baseline to Week 48
measure: Number of Participants With Acquisition of Resistance to EFV Categorized by AUC Relationship - Evaluable Pharmacokinetic Population
timeFrame: Baseline to Week 48
measure: Cmax and Cmin of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: AUC (TAU) of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: CLT/F of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: CLT/F/kg of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: Terminal Phase Elimination Half-life (T-HALF) in Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
timeFrame: Week 2
measure: The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants
timeFrame: Weeks 60, 72, 84, and 96
measure: The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants
timeFrame: Weeks 60, 72, 84, and 96
measure: Log10 c/mL HIV RNA Changes From Baseline at Weeks 60, 72, 84 and 96 - Treated Participants
timeFrame: Baseline through Weeks 60, 72, 84, and 96
measure: CD4 Cell Count Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants
timeFrame: Baseline to Weeks 60, 72, 84, and 96
measure: Percent of CD4 Cells Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants
timeFrame: Baseline to Weeks 60, 72, 84, and 96
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Capital Federal
country: Argentina
facility: Local Institution
city: Cali
country: Colombia
facility: Local Institution
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Morelia
country: Mexico
facility: Local Institution
state: Michioacan
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Colima
country: Mexico
facility: Local Institution
city: Puebla
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Ciudad De Panama
country: Panama
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: Free State
city: Westdene
country: South Africa
facility: Local Institution
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution
state: Western Cape
city: Bangkok
country: Thailand
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Pavia-Ruz N, Rossouw M, Saez-Llorens X, Bunupuradah T, Taylor M, Yang R, Sevinsky H, Krystal M, Lataillade M, Seekins D, Biguenet S. Efavirenz Capsule Sprinkle and Liquid Formulations With Didanosine and Emtricitabine in HIV-1-infected Infants and Children 3 Months to 6 Years of Age: Study AI266-922. Pediatr Infect Dis J. 2015 Dec;34(12):1355-60. doi: 10.1097/INF.0000000000000913.