- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01837719
Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat (Atazanavir)
August 19, 2014 updated by: Bristol-Myers Squibb
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
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 Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
64
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Texas
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Austin, Texas, United States, 78744
- Ppd Development, Inc.
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 49 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment A: Atazanavir + Cobicistat coadministered
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
|
300-mg capsule
Other Names:
150-mg tablet
|
Experimental: Treatment B: Atazanavir/Cobicistat FDC
Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8
|
Atazanavir 300-mg/cobicistat 150-mg FDC tablet
|
Experimental: Treatment C: Atazanavir + Cobicistat coadministered
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
|
300-mg capsule
Other Names:
150-mg tablet
|
Experimental: Treatment D: Atazanavir/Cobicistat FDC
Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22
|
Atazanavir 300-mg/cobicistat 150-mg FDC tablet
|
Experimental: Treatment E: Atazanavir/Cobicistat FDC
Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
|
Atazanavir 300-mg/cobicistat 150-mg FDC tablet
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of Atazanavir
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)
|
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
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)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Died and With Serious Adverse Events (SAEs)
Time Frame: On Day 24 or 31
|
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.
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On Day 24 or 31
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Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Time Frame: At Screening and on Days -1,4, 11, 18, and 31 (study discharge)
|
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.
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At Screening and on Days -1,4, 11, 18, and 31 (study discharge)
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Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings
Time Frame: At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31)
|
A 12-lead ECG was recorded at predose and 4 hours post dose at screening, Days -1, 1, 8 15, 22, 29 and study discharge.
ECGs were recorded after the patient had been supine for at least 5 minutes.
All ECG readings post dosing (including unscheduled) were included.
|
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
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)
|
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.
Tmax 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)
|
Observed Concentration at 24 Hours (C24) of Atazanavir
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)
|
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.
C24 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)
|
Apparent Terminal Half-life (T-HALF) of Atazanavir
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)
|
Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29.
T-HALF 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)
|
Maximum Observed Plasma Concentration (Cmax) of Cobicistat
Time Frame: 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)
|
Blood samples for testing 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 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
|
Time of Maximum Observed Concentration (Tmax) of Cobicistat
Time Frame: 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)
|
Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29.
Tmax was derived from plasma concentration versus time data.
|
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)
|
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
Time Frame: 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)
|
Blood samples for testing 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 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)
|
T-HALF of Cobicistat
Time Frame: 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)
|
Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29.
T-HALF was derived from plasma concentration versus time data.
|
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)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2013
Primary Completion (Actual)
June 1, 2013
Study Completion (Actual)
June 1, 2013
Study Registration Dates
First Submitted
April 18, 2013
First Submitted That Met QC Criteria
April 22, 2013
First Posted (Estimate)
April 23, 2013
Study Record Updates
Last Update Posted (Estimate)
August 29, 2014
Last Update Submitted That Met QC Criteria
August 19, 2014
Last Verified
August 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Cobicistat
- Atazanavir Sulfate
Other Study ID Numbers
- AI424-511
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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