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

NCT00364793 | Completed Phase 1 Results

• 1 other identifier: AI266-922
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 17

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.

Conditions

HIV Infections

Keywords

HIV, Pediatric

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population

  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.

  Week 2

• 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

  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).

  Week 2

• Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population

  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).

  Week 2

• Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population

  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).

  Week 2

Secondary Outcomes (24)

• 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

  Week 48

• The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 48 as Analyzed by Different Algorithms - All Treated Participants

  Week 48

• The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants

  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

  Week 24

• Log10 c/mL HIV RNA Changes From Baseline Through Week 48 - Treated Participants

  Baseline through Week 48

Study Arms (4)

EFV+ddI+FTC in patients >= 3 months to < 6 months

EXPERIMENTAL

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)

EFV+ddI+FTC in patients >=6 months to < 2 years

EXPERIMENTAL

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)

EFV+ddI+FTC in patients >= 2 years to < 3 years

EXPERIMENTAL

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)

EFV+ddI+FTC in patients >= 3 years to <= 6 years

EXPERIMENTAL

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)

Interventions

Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) DRUG

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)

Also known as: Sustiva, BMS-561525

EFV+ddI+FTC in patients >= 2 years to < 3 years; EFV+ddI+FTC in patients >= 3 months to < 6 months; EFV+ddI+FTC in patients >= 3 years to <= 6 years; EFV+ddI+FTC in patients >=6 months to < 2 years

Eligibility Criteria

• Age: 3 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (17)

Local Institution

Buenos Aires, Buenos Aires, 1425, Argentina

Location

Local Institution

Capital Federal, 1425, Argentina

Location

Local Institution

Cali, Colombia

Location

Local Institution

Colima, Colima, 28019, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44280, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44520, Mexico

Location

Local Institution

Df, Mexico City, 06720, Mexico

Location

Local Institution

Morelia, Michioacan, 58000, Mexico

Location

Local Institution

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution

Puebla City, Puebla, 72000, Mexico

Location

Local Institution

San Luis Potosí City, 78240, Mexico

Location

Local Institution

Panama City, 0816-00383, Panama

Location

Local Institution

Bloemfontein, Free State, 9301, South Africa

Location

Local Institution

Westdene, Gauteng, 2092, South Africa

Location

Local Institution

Cape Town, Western Cape, 7505, South Africa

Location

Local Institution

Bangkok, 10330, Thailand

Location

Local Institution

Bangkok, 10700, Thailand

Location

Related Publications (1)

• 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.

  PMID: 26379163 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

HIV Infections

Interventions

efavirenz; Didanosine; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2006
• First Posted: August 16, 2006
• Study Start: February 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: July 1, 2013
• Last Updated: April 29, 2014
• Results First Posted: April 11, 2014

Record last verified: 2014-04

Locations

ZA (3); ME (8); PA (1); AR (2); TH (2); CO (1)