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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atazanavir | Drug | 300-mg capsule |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
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
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:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ppd Development, Inc. | Austin | Texas | 78744 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25361436 | Derived | 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. |
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A total of 149 patients were enrolled and 64 randomized to 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC), with a 7-day washout period between treatments. Approximately 32 were to be discharged after Period 4, based on treatment sequence. Those remaining were to continue to and be discharged at end of Period 5.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants Who Received Treatment | All participants who received atazanavir with cobicistat in 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC). Treatment A: 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 B: 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 C: Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day15 or 22. Treatment D: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22. Treatment E: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1: Days 1-7 (Treatment A or B) |
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| Cobicistat | Drug | 150-mg tablet |
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| Atazanavir/Cobicistat FDC | Drug | Atazanavir 300-mg/cobicistat 150-mg FDC tablet |
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| 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) |
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| NOT COMPLETED |
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| Period 2: Days 8-14 (Treatment B or A) |
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| Period 3: Days 15-21 (Treatment C or D) |
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| Period 4: Days 22-28 (Treatment D or C) |
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| Period 5: Days 29-31 (Treatment E) |
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All participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants Who Received Treatment | All participants who received atazanavir with cobicistat in 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC). Treatment A: 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 B: 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 C: 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 D: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day15 or 29. Treatment E: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Body mass index | Mean | Standard Deviation | kg/m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Primary | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
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| Secondary | 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. | All participants who received at least 1 dose of any study drug. | Posted | Number | Participants | On Day 24 or 31 |
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| Secondary | 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. | All participants who received at least 1 dose of study drug and had laboratory test results available. | Posted | Number | Participants | At Screening and on Days -1,4, 11, 18, and 31 (study discharge) |
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| Secondary | Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings | 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. | All participants who received at least 1 dose of study medication and were evaluable. | Posted | Number | Participants | At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31) |
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| Secondary | Time of Maximum Observed Concentration (Tmax) 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. Tmax was derived from plasma concentration versus time data. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Median | Full Range | Hours | 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) |
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| Secondary | Observed Concentration at 24 Hours (C24) 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. C24 was derived from plasma concentration versus time data. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Apparent Terminal Half-life (T-HALF) of Atazanavir | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Mean | Standard Deviation | Hours | 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) |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Cobicistat | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Time of Maximum Observed Concentration (Tmax) of Cobicistat | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Median | Full Range | Hours | 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) |
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| Secondary | 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 | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. n=evaluable participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
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| Secondary | T-HALF of Cobicistat | 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. | All participants who received any study medication and had any available concentration-time data. All available derived pharmacokinetic (PK) parameter values were included in the PK data set and reported, but only those with adequate PK profiles were included in the summary statistics and statistical analysis. | Posted | Mean | Standard Deviation | Hours | 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) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 64 | 1 | 64 | ||
| EG001 | 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. | 0 | 64 | 3 | 64 | ||
| EG002 | 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. | 0 | 63 | 0 | 63 | ||
| EG003 | 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. | 0 | 63 | 0 | 63 | ||
| EG004 | 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. | 0 | 31 | 0 | 31 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069446 | Atazanavir Sulfate |
| D000069547 | Cobicistat |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
Not provided
Not provided
| Asian |
|
| A linear mixed-effect model with treatment as fixed effects and participant as a random effect will be used to estimate the effect of a light meal and the fasted state on the natural logarithms of exposure of atazanavir when given as an FDC | Mixed Models Analysis | Geometric mean ratio | 1.423 | 2-Sided | 90 | 1.273 | 1.590 | Geometric mean ratio was calculated as Treatment B/Treatment D | No | Superiority or Other |
| To assess the relative bioavailability of atazanavir under fasted (Treatment D) versus fed (Treatment C) states, a linear mixed-effects model was applied to the natural logarithms of atazanavir Cmax with treatment, period, and sequence as fixed effects and participant (sequence) as a random effect. | Mixed Models Analysis | Geometric mean ratio | 1.137 | 2-Sided | 90 | 1.000 | 1.292 | Geometric mean ratio is calculated as Treatment D/Treatment C | No | Superiority or Other |
| A linear mixed-effect model with treatment as fixed effects and participant as a random effect will be used to estimate the effect of a high fat meal and the fasted state on the natural logarithms of exposure of atazanavir when given as an FDC | Mixed Models Analysis | Geometric mean ratio | 0.862 | 2-Sided | 90 | 0.701 | 1.059 | Geometric mean ratio is calculated as Treatment E/Treatment D | No | Superiority or Other |
| A linear mixed-effect model with treatment as fixed effects and participant as a random effect will be used to estimate the effect of high fat and light meals on the natural logarithms of exposure of atazanavir when given as an FDC | Mixed Models Analysis | Geometric mean ratio | 0.643 | 2-Sided | 90 | 0.545 | 0.759 | Geometric mean ratio is calculated as Treatment E/Treatment B | No | Superiority or Other |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
|
|
|
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 |
| OG003 | 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 |
| OG004 | 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 |
|
|
| 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
|
|
| OG003 | 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 |
| OG004 | 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 |
|
|
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 |
| OG003 | Treatment D: Atazanavir/Cobicistat FDC | Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day15 or 22 |
| OG004 | 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 |
|
|
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 |
| OG003 | 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 |
| OG004 | 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 |
|
|
|
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 |
| OG003 | 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 |
| OG004 | 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 |
|
|
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 |
| OG003 | Treatment D: Atazanavir/Cobicistat FDC | Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day15 or22 |
| OG004 | 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 |
|
|
|
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
| OG003 | 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 |
| OG004 | 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 |
|
|
| OG002 |
| 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 |
| OG003 | Treatment D: Atazanavir/Cobicistat FDC | Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day15 or 22 |
| OG004 | 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 |
|
|
|
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
| OG003 | 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 |
| OG004 | 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 |
|
|