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

NCT01837719 | Completed Phase 1 Results

• 1 other identifier: AI424-511
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1)

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of Atazanavir

  Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Cmax was derived from plasma concentration versus time data.

  Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

• Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and From Time 0 to Infinity (AUC[INF]) for Atazanavir

  Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. AUC(0-T) and AUC(INF) were derived from plasma concentration versus time data.

  Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

Secondary Outcomes (10)

• Number of Participants Who Died and With Serious Adverse Events (SAEs)

  On Day 24 or 31

• Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests

  At Screening and on Days -1,4, 11, 18, and 31 (study discharge)

• Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings

  At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31)

• Time of Maximum Observed Concentration (Tmax) of Atazanavir

  Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

• Observed Concentration at 24 Hours (C24) of Atazanavir

  Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

Study Arms (5)

Treatment A: Atazanavir + Cobicistat coadministered

EXPERIMENTAL

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

Drug: Atazanavir; Drug: Cobicistat

Treatment B: Atazanavir/Cobicistat FDC

EXPERIMENTAL

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

Drug: Atazanavir/Cobicistat FDC

Treatment C: Atazanavir + Cobicistat coadministered

EXPERIMENTAL

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

Drug: Atazanavir; Drug: Cobicistat

Treatment D: Atazanavir/Cobicistat FDC

EXPERIMENTAL

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

Drug: Atazanavir/Cobicistat FDC

Treatment E: Atazanavir/Cobicistat FDC

EXPERIMENTAL

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

Drug: Atazanavir/Cobicistat FDC

Interventions

Atazanavir DRUG

300-mg capsule

Also known as: BMS-232632

Treatment A: Atazanavir + Cobicistat coadministered; Treatment C: Atazanavir + Cobicistat coadministered

Cobicistat DRUG

150-mg tablet

Treatment A: Atazanavir + Cobicistat coadministered; Treatment C: Atazanavir + Cobicistat coadministered

Atazanavir/Cobicistat FDC DRUG

Atazanavir 300-mg/cobicistat 150-mg FDC tablet

Treatment B: Atazanavir/Cobicistat FDC; Treatment D: Atazanavir/Cobicistat FDC; Treatment E: Atazanavir/Cobicistat FDC

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• nd- or 3rd-degree A-V block or clinically relevant abnormalities in ECG findings
• Positive result on urine screening for drugs of abuse

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Ppd Development, Inc.

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Sevinsky H, Tao X, Wang R, Ravindran P, Sims K, Xu X, Jariwala N, Bertz R. A randomized trial in healthy subjects to assess the bioequivalence of an atazanavir/cobicistat fixed-dose combination tablet versus administration as separate agents. Antivir Ther. 2015;20(5):493-500. doi: 10.3851/IMP2913. Epub 2014 Oct 31.

  PMID: 25361436 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Atazanavir Sulfate; Cobicistat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles

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: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: April 23, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 29, 2014
• Results First Posted: August 29, 2014

Record last verified: 2014-08

Locations

US (1)