Safety, Tolerability and Pharmacokinetics of Efavirenz in HIV-Infected Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00364793
First received: August 15, 2006
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Cmax and Cmin were derived from plasma concentrations versus time using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.

  • 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 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was < LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in micromolars*time (µM•h).

  • Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations of EFV were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F was calculated by dividing the dose of EFV by AUC(TAU) of EFV. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).

  • Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations of EFV were determined using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).


Secondary Outcome Measures:
  • 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 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA < 400 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA < 400 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were < 400 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA < 400 c/mL in the predefined Week 48 visit window; denominator was all treated participants.

  • The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 48 as Analyzed by Different Algorithms - All Treated Participants [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA < 50 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA < 50 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were < 50 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA < 50 c/mL in the predefined Week 48 visit window; denominator was all treated participants.

  • The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA < 400 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA < 400 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were < 400 c/mL; denominator was all who remained on treatment through Week 24.

  • The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA < 50 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA < 50 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were < 50 c/mL; denominator was all who remained on treatment through Week 24.

  • Log10 c/mL HIV RNA Changes From Baseline Through Week 48 - Treated Participants [ Time Frame: Baseline through Week 48 ] [ Designated as safety issue: No ]
    HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • CD4 Cell Count Change From Baseline at Weeks 24 and 48 - Treated Participants [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
    A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • Percent of CD4 Cells Change From Baseline at Weeks 24 and 48 - Treated Participants [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
    A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • 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 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]
    Center for Disease Control and Prevention (CDC) classification of Class C events used to define acquired immunodeficiency syndrome (AIDS): include pneumocystis pneumonia, pneumonia, pulmonary tuberculosis. AE=new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. AE Severity: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling (Division of AIDs Table, published December 2004). Baseline=within 50 days post screening, prior to start of study drug. 2 categories for death presented (on-treatment and enrolled/not treated).

  • Number of Participants With Liver Function Test Laboratory Abnormalities - Treated Population [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]
    Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. Division of AIDS Table (DAIDS) for Grading Severity of Adult and Pediatric AEs version (v) Dec 2004. Upper limit of normal (ULN): lower limit of normal (LLN), alanine transaminase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). ALT Grade (Gr) 1: 1.25 to 2.5*ULN; Gr 2: 2.6 to 5.0*ULN; Gr 3: 5.1 to 10.0*ULN; Gr 4: >10.0*ULN. AST Gr 1: 1.25 to 2.5*ULN; Gr 2: 2.6 to 5.0*ULN; Gr 3: 5.1 to 10.0*ULN; Gr 4: >10.0*ULN. Total bilirubin Gr 1: 1.25 to 1.5*ULN; Gr 2: 1.6 to 2.5*ULN; Gr 3: 2.6 to 5.0*ULN; Gr 4: >5.0*ULN. ALP (U/L) Gr 1: 1.25 to 2.5*ULN, Gr 2: 2.6 to 5.0*ULN, Gr 3: 5.1 to 10.0*ULN, Gr 4: >10.0*ULN. Albumin (low) Gr 1: 3 grams per deciliter (g/dL) to <LLN ; Gr 2: 2.0-2.9 g/dL; Gr 3: < 2 g/dL. Gr 4: Not applicable. Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • Number of Participants With Lipid and Glucose Laboratory Abnormalities - Treated Participants [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]
    Abnormalities were determined from measurements analyzed at central or local laboratory. DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Total Cholesterol (fasting) Gr 1: 170 - 199 mg/dL; Gr 2: 200 - 300 mg/dL; Gr 3 >300 mg/dL; Gr 4 Not Applicable(NA). LDL cholesterol, fasting: Gr 1: 110-129 mg/dL; Gr 2: 130-189 mg/dL; Gr 3 >=190 mg/dL; Gr 4 NA. Triglycerides, fasting: Gr 1: NA; Gr 2 500-750 mg/dL; Gr 3: 751-1,200 mg/dL; Gr 4: >1,200 mg/dL. Glucose, serum, high, fasting and (non-fasting): Gr 1: 110 - 125 (116-160) mg/dL; Gr 2: 126-250 (161- 250) mg/dL; Gr 3: 251-500 (251-500) mg/dL; Gr 4: >500 (> 500) mg/dL. Glucose, serum, low, >=1 month of age (<1 month): Gr 1: 55-64 (50-54) mg/dL; Gr 2: 40-54 (40-49) mg/dL; Gr 3: 30-39 (30-39) mg/dL; Gr 4: <30 (<30) mg/dL. Baseline: within 50 days after the screening visit and was prior to start of study medication (Week 1). Only those in 4th arm were old enough to fast prior to testing; other arms did not have fasting samples taken.

  • Number of Participants With Serum Chemistry Abnormalities - Treated Participants [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]
    Central/local laboratory. DAIDS v 2004. Bicarbonate, low: Gr 1: 16 milliequivalents per liter (mEq/L) - < LLN; Gr 2: 11.0-15.9 mEq/L; Gr 3: 8.0-10.9 mEq/L; Gr 4: <8.0 mEq/L; calcium, high Gr 1: 10.6-11.5 mg/dL; Gr 2: 11.6-12.5 mg/dL; Gr 3 12.6-13.5 mg/dL; Gr 4: >13.5 mg/dL; calcium, low Gr1: 7.8-8.4 mg/dL; Gr2: 7.0-7.7 mg/dL; Gr3: 6.1-6.9 mg/dL; Gr 4: <6.1 mg/dL; creatinine Gr1: 1.1-1.3*ULN; Gr 2: 1.4-1.8*ULN; Gr 3: 1.9-3.4*ULN; Gr 4: >=3.5*ULN; lipase Gr 1: 1.1-1.5*ULN; Gr 2: 1.6-3.0*ULN; Gr 3: 3.1-5.0*ULN; Gr 4: >5.0*ULN; potassium high (low) Gr 1: 5.6-6.0 (3.0-3.4) mEq/L; Gr 2: 6.1-6.5 (2.5-2.9) mEq/L; Gr 3: 6.6-7.0 (2.0-2.4) mEq/L; Gr 4: >7.0 (<2.0) mEq/L; sodium, high (low) Gr 1: 146-150 (130-135) mEq/L; Gr 2: 151-154 (125-129) mEq/L; Gr 3: 155-159 (121-124) mEq/L; Gr 4: >=160 (<=120) mEq/L; uric acid Gr 1: 7.5-10.0 mg/dL; Gr 2: 10.1-12.0 mg/dL; Gr 3: 12.1-15.0 mg/dL; Gr 4: >15.0 mg/dL. Baseline within 50 days post screening, prior to start of study medication.

  • Number of Participants With Hematologic Abnormalities - Treated Participants [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]
    Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. DAIDS DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Hemoglobin Gr 1: 8.5-10.0 g/dL; Gr 2: 7.5-8.4 g/dL; Gr 3: 6.50-7.4 g/dL; Gr 4: <6.5 g/dL; Platelets, decreased: Gr 1: 100.000-124.999*10^9/L; Gr 2: 50.000-99.999*10^9/L; Gr 3: 25.000-49.999*10^9/L; Gr 4: <25.000*10^9/L; White blood cell count (WBC) decreased Gr 1: 2.000-2.500*10^9/L; Gr 2: 1.500-1.999*10^9/L; Gr 3: 1.000-1.499*10^9/L; Gr 4: <1.000*10^9/L. Baseline visit was within 50 days post screening and was prior to start of study drug (Week 1).

  • Number of Treated Participants With Resistance Associated Genotypic and Phenotypic Changes in Viruses - Participants With Virologic Failure, Lack of Suppression or Viral Load Rebound [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    At baseline, treatment-naïve screened by genotype; treatment-experienced screened by genotype and phenotype. Genotypic resistance: presence of substitutions in reverse transcriptase (RT) gene and/or presence of mutations that confer resistance to nucleoside reverse transcriptase inhibitor class. Phenotype resistance: FTC: > 3.1* the 50% inhibitory concentration (IC50) of the control strain; EFV: > 3.3* IC50 ; ddI: > 2.6*IC50. Virologic failure: <1 log10 decrease in HIV RNA from Week 16 on; confirmatory HIV RNA within 14-35 days; HIV RNA > 10,000 c/mL with prior value < 400 c/mL; confirmatory HIV RNA 14-35 days. Monogram Biosciences Phenosense™ assay ( EFV and FTC: biologic cutoffs=3 and 3.5, respectively; ddI: clinical cutoff: lower limit=1.39; upper limit = 2.2.); VircoTYPE™ HIV-1 v 4.3.01( EFV, FTC: biologic cutoffs=3.3 and 3.1, respectively;ddI: clinical cutoff: lower limit = 0.9; upper limit = 2.6. No genotypic/phenotypic changes in presence of virologic failure=no resistance.

  • Number of Participants With Acquisition of Resistance to EFV Categorized by AUC Relationship - Evaluable Pharmacokinetic Population [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    PK parameters were evaluated 2 weeks post start of dosing. Based on observed AUC, measured in micromoles (μM)*h, dosing was increased, remained the same, or decreased at next visit to achieve the desired AUC (110-380 μM*h). Number of participants who became resistant was categorized by those who required additional dosing after Week 2 (AUC<110 μM*h) and those who did not. AUC: derived from plasma concentration of EFV versus time. Plasma concentrations for determination of AUC were obtained using a validated LC-MS/MS method. LLOQ for EFV = 10.0 ng/mL and ULOQ = 8,000 ng/mL. AUC calculated by log- and linear trapezoidal summations. Genotypic resistance=presence of substitutions in the RT gene and/or presence of mutations that confer resistance to entire nucleoside reverse transcriptase inhibitor class. Phenotypic resistance=EFV: > 3.3* IC50 of control strain. Assays: Monogram Biosciences Phenosense™ GT (EFV biologic cutoff=3) and VircoTYPE™ HIV-1 v 4.3.01( EFV biologic cutoff=3.3).

  • Cmax and Cmin of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Cmax and Cmin were derived from plasma concentration versus time. Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. All reportable Cmin values were <LLOQ in all age groups except >=6 months to < 2 years (Group 2); LLOQ/2 was imputed for those summary statistics;in Group 2, 9 of 10 Cmin values were <LLOQ; LLOQ/2 was imputed for those samples for summary statistics. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.

  • AUC (TAU) of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations were obtained using a validated LC-MS/MS at Week 2. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was < LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in nanograms*time per milliliter (ng•h/mL).

  • CLT/F of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F was calculated by dividing the dose of ddI by AUC(TAU) of ddI. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).

  • CLT/F/kg of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).

  • Terminal Phase Elimination Half-life (T-HALF) in Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the T-HALF was summarized using a mean. Terminal elimination plasma half-life=ln2 divided by K where K is the absolute value of the slope of the terminal phase of the plasma profile as determined by log-linear regression of at least three data points. T-HALF was measured in hours (h).

  • The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants [ Time Frame: Weeks 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA < 400 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were < 400 c/mL; denominator was all who remained on treatment through the specific week.

  • The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants [ Time Frame: Weeks 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA < 50 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were < 50 c/mL; denominator was all who remained on treatment through the specific week.

  • Log10 c/mL HIV RNA Changes From Baseline at Weeks 60, 72, 84 and 96 - Treated Participants [ Time Frame: Baseline through Weeks 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • CD4 Cell Count Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants [ Time Frame: Baseline to Weeks 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).

  • Percent of CD4 Cells Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants [ Time Frame: Baseline to Weeks 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).


Enrollment: 56
Study Start Date: February 2007
Study Completion Date: July 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EFV+ddI+FTC in patients >= 3 months to < 6 months
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)

Oral Solution, Capsules or Tablets, Oral, once daily

Efavirenz (EFV) per weight-based dosing nomogram (max 720 mg)

Didanosine (ddI) 240 mg/m2 (max 400 mg)

Emtricitabine (FTC) 6 mg/kg (max 200 mg)

Where EFV oral solution is commercially available: 48 weeks or until 3rd birthday (whichever is longer);

Where EFV oral solution NOT commercially available: until 7th birthday or until able to swallow EFV capsules (whichever occurs first)

Other Names:
  • Sustiva
  • BMS-561525
Experimental: EFV+ddI+FTC in patients >=6 months to < 2 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)

Oral Solution, Capsules or Tablets, Oral, once daily

Efavirenz (EFV) per weight-based dosing nomogram (max 720 mg)

Didanosine (ddI) 240 mg/m2 (max 400 mg)

Emtricitabine (FTC) 6 mg/kg (max 200 mg)

Where EFV oral solution is commercially available: 48 weeks or until 3rd birthday (whichever is longer);

Where EFV oral solution NOT commercially available: until 7th birthday or until able to swallow EFV capsules (whichever occurs first)

Other Names:
  • Sustiva
  • BMS-561525
Experimental: EFV+ddI+FTC in patients >= 2 years to < 3 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)

Oral Solution, Capsules or Tablets, Oral, once daily

Efavirenz (EFV) per weight-based dosing nomogram (max 720 mg)

Didanosine (ddI) 240 mg/m2 (max 400 mg)

Emtricitabine (FTC) 6 mg/kg (max 200 mg)

Where EFV oral solution is commercially available: 48 weeks or until 3rd birthday (whichever is longer);

Where EFV oral solution NOT commercially available: until 7th birthday or until able to swallow EFV capsules (whichever occurs first)

Other Names:
  • Sustiva
  • BMS-561525
Experimental: EFV+ddI+FTC in patients >= 3 years to <= 6 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)

Oral Solution, Capsules or Tablets, Oral, once daily

Efavirenz (EFV) per weight-based dosing nomogram (max 720 mg)

Didanosine (ddI) 240 mg/m2 (max 400 mg)

Emtricitabine (FTC) 6 mg/kg (max 200 mg)

Where EFV oral solution is commercially available: 48 weeks or until 3rd birthday (whichever is longer);

Where EFV oral solution NOT commercially available: until 7th birthday or until able to swallow EFV capsules (whichever occurs first)

Other Names:
  • Sustiva
  • BMS-561525

  Eligibility

Ages Eligible for Study:   3 Months to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364793

Locations
Argentina
Local Institution
Buenos Aires, Argentina, 1425
Local Institution
Capital Federal, Argentina, 1425
Colombia
Local Institution
Cali, Colombia
Mexico
Local Institution
Df, Distrito Federal, Mexico, 06720
Local Institution
Guadalajara, Jalisco, Mexico, 44520
Local Institution
Guadalajara, Jalisco, Mexico, 44280
Local Institution
Morelia, Michioacan, Mexico, 58000
Local Institution
Monterrey, Nuevo Leon, Mexico, 64460
Local Institution
Colima, Mexico, 28019
Local Institution
Puebla, Mexico, 72000
Local Institution
San Luis Potosi, Mexico, 78240
Panama
Local Institution
Ciudad De Panama, Panama, 0816-00383
South Africa
Local Institution
Bloemfontein, Free State, South Africa, 9301
Local Institution
Westdene, Gauteng, South Africa, 2092
Local Institution
Cape Town, Western Cape, South Africa, 7505
Thailand
Local Institution
Bangkok, Thailand, 10700
Local Institution
Bangkok, Thailand, 10330
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00364793     History of Changes
Other Study ID Numbers: AI266-922
Study First Received: August 15, 2006
Results First Received: March 6, 2014
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
HIV, Pediatric

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Didanosine
Efavirenz
Emtricitabine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014