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

Bristol-Myers Squibb64 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1)

Interventions

AtazanavirDRUG

300-mg capsule

CobicistatDRUG

150-mg tablet

Atazanavir/Cobicistat FDCDRUG

Atazanavir 300-mg/cobicistat 150-mg FDC tablet

Eligibility

Sex: ALLMin age: 18 YearsMax age: 49 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Ppd Development, Inc.

Austin, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Secondary Outcomes

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

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant who receives an investigational product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. An SAE is any untoward medical occurrence that at any dose results in death; is life-threatening; or requires or prolongs inpatient hospitalization.

Time frame: On Day 24 or 31

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

LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment; h=high; hpf=high power field. Abnormal criteria: Leukocytes, low (\*10\^3 c/uL): \<0.85\*preRx if preRx\<LLN; \<0.9\*LLN if LLN≤preRx≤ULN;\< 0.9\*LLN if preRx=missing;\<LLN if preRX\>ULN. Neutrophils, low (\*10\^3 c/uL): \<0.85\*preRx if preRx\<1.5; \<1.5 if preRx=missing; \<1.5 if preRx ≥1.5. Bilirubin, h (mg/dL): \>1.1\* ULN if preRx≤ULN; \>1.1\*ULN if preRx=missing; \>1.25\*preRx if preRx\>ULN. Bilirubin, h (mg/dL): \>1.1\* ULN if preRx≤ULN; \>1.1\*ULN if preRx=missing; \>1.25\*preRx if preRx\>ULN. Blood, urine, h: ≥2\*preRx if preRx≥1; ≥2 if preRx \<1; ≥2 if preRx=missing. RBCs/WBCs, h (hpf): ≥2 if preRx=missing ≥2 if preRx\<2 ≥4 if preRx ≥2. Creatine kinase, h (U/L): \>1.5\*preRx if preRx\>ULN; \>1.5\*ULN if preRx≤ULN; \>1.5\*ULN if preRx=missing; AST, h (U/L): \>1.25\* preRx if preRx\>ULN; \>1.25\*ULN if preRx≤ULN; \>1.25\*ULN if preRx=missing. Lactate dehydrogenase, h (U/L): \>1.25\*ULN if preRx≤ULN; \>1.25\*ULN if preRx=missing; \>1.5\*preRx if preRx\>ULN.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.