Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)

Treatments: Drug: Atazanavir/Cobicistat FDC; Drug: Atazanavir; Drug: Cobicistat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01837719

AI424-511

Details and patient eligibility

About

The purpose of the study is to compare the pharmacokinetics and bioequivalence of atazanavir in a fixed-dose combination with cobicistat with that of atazanavir coadministered with cobicistat as single agents.

Enrollment: 64 patients

Sex: All

Ages: 18 to 49 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Healthy men and women, ages 18 to 49 years
• Body mass index 18 to 32 kg/m^2, inclusive
• Women of childbearing potential (WOCBP) who were not pregnant or breastfeeding
• WOCBP and men who are sexually active with WOCBP must use acceptable contraceptive methods

Key Exclusion Criteria:

• Any significant acute or chronic medical illness

• Current or recent (within 3 months of study drug administration) gastrointestinal tract disease

• Any major surgery within 4 weeks of study drug administration

• Any gastrointestinal tract surgery (including cholecystectomy) that could have an impact on the absorption of study drug

• Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only)

• Blood transfusion within 4 weeks of study drug administration

• Inability to tolerate oral medication, to be venipunctured, or to tolerate venous access

• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination or electrocardiogram (ECG) findings, vital sign measurements, or results of clinical laboratory tests, beyond what is consistent with the target population

• Any of the following 12-lead ECG findings prior to study drug administration, confirmed by repeat testing

  • PR ≥210 msec
  • QRS ≥120 msec
  • QT ≥500 msec
  • QTcF ≥450 msec

• 2nd- or 3rd-degree A-V block or clinically relevant abnormalities in ECG findings

• Positive result on urine screening for drugs of abuse

• Positive result on blood screening for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or -2 antibody

• Laboratory test results indicating levels outside of the ranges specified below:

  • Alanine aminotransferase >upper limit of normal (ULN)
  • Aspartate aminotransferase >ULN
  • Total bilirubin >ULN
  • Serum creatinine >ULN

Trial design

64 participants in 5 patient groups

Treatment A: Atazanavir + Cobicistat coadministered

Experimental group

Description:

Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, following a light meal on Day 1 or 8

Treatment:

Drug: Atazanavir

Drug: Cobicistat

Treatment B: Atazanavir/Cobicistat FDC

Experimental group

Description:

Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8

Treatment:

Drug: Atazanavir/Cobicistat FDC

Treatment C: Atazanavir + Cobicistat coadministered

Experimental group

Description:

Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day 15 or 22

Treatment:

Drug: Atazanavir

Drug: Cobicistat

Treatment D: Atazanavir/Cobicistat FDC

Experimental group

Description:

Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22

Treatment:

Drug: Atazanavir/Cobicistat FDC

Treatment E: Atazanavir/Cobicistat FDC

Experimental group

Description:

Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29

Treatment:

Drug: Atazanavir/Cobicistat FDC