Clinical trial NCT01837719: Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat
Official title: A Randomized, 5-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Following a Light Meal, the Relative Bioavailability of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Under Fasted Conditions, and the Effect of Food on the Bioavailability of Atazanavir in the Fixed Dose Combination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-04-23
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


Eligibility 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Atazanavir
timeFrame: 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)
measure: 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
timeFrame: 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:
measure: Number of Participants Who Died and With Serious Adverse Events (SAEs)
timeFrame: On Day 24 or 31
measure: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
timeFrame: At Screening and on Days -1,4, 11, 18, and 31 (study discharge)
measure: Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings
timeFrame: At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31)
measure: Time of Maximum Observed Concentration (Tmax) of Atazanavir
timeFrame: 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)
measure: Observed Concentration at 24 Hours (C24) of Atazanavir
timeFrame: 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)
measure: Apparent Terminal Half-life (T-HALF) of Atazanavir
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of Cobicistat
timeFrame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
measure: Time of Maximum Observed Concentration (Tmax) of Cobicistat
timeFrame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
measure: Area Under the Concentration Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and Area Under the Concentration Curve From Time 0 to Infinity (AUC[INF]) of Cobicistat
timeFrame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
measure: T-HALF of Cobicistat
timeFrame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
Other outcomes:
Locations:
city: Austin
country: United States
facility: Ppd Development, Inc.
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.