Trial Outcomes & Findings for Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat (NCT NCT01837719)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

64 participants

Primary outcome 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)

Results posted on

2014-08-29

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Period 1: Days 1-7 (Treatment A or B) STARTED	64
Period 1: Days 1-7 (Treatment A or B) COMPLETED	64
Period 1: Days 1-7 (Treatment A or B) NOT COMPLETED	0
Period 2: Days 8-14 (Treatment B or A) STARTED	64
Period 2: Days 8-14 (Treatment B or A) COMPLETED	63
Period 2: Days 8-14 (Treatment B or A) NOT COMPLETED	1
Period 3: Days 15-21 (Treatment C or D) STARTED	63
Period 3: Days 15-21 (Treatment C or D) COMPLETED	63
Period 3: Days 15-21 (Treatment C or D) NOT COMPLETED	0
Period 4: Days 22-28 (Treatment D or C) STARTED	63
Period 4: Days 22-28 (Treatment D or C) COMPLETED	63
Period 4: Days 22-28 (Treatment D or C) NOT COMPLETED	0
Period 5: Days 29-31 (Treatment E) STARTED	31
Period 5: Days 29-31 (Treatment E) COMPLETED	30
Period 5: Days 29-31 (Treatment E) NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Period 2: Days 8-14 (Treatment B or A) Withdrawal by Subject	1
Period 5: Days 29-31 (Treatment E) Poor compliance/noncompliance	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants Who Received Treatment n=64 Participants 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.
Age, Continuous	32.5 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Race/Ethnicity, Customized White	29 Participants n=5 Participants
Race/Ethnicity, Customized Black	33 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Body mass index	26.5 kg/m^2 STANDARD_DEVIATION 2.9 • n=5 Participants

PRIMARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Maximum Observed Plasma Concentration (Cmax) of Atazanavir	3832 ng/mL Geometric Coefficient of Variation 39	4104 ng/mL Geometric Coefficient of Variation 32	2585 ng/mL Geometric Coefficient of Variation 45	2941 ng/mL Geometric Coefficient of Variation 44	2545 ng/mL Geometric Coefficient of Variation 43

PRIMARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
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 AUC(0-T)	32775 ng*h/mL Geometric Coefficient of Variation 38	34905 ng*h/mL Geometric Coefficient of Variation 32	25017 ng*h/mL Geometric Coefficient of Variation 46	27875 ng*h/mL Geometric Coefficient of Variation 41	25873 ng*h/mL Geometric Coefficient of Variation 40
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 AUC(0-INF)	33523 ng*h/mL Geometric Coefficient of Variation 39	35673 ng*h/mL Geometric Coefficient of Variation 32	25547 ng*h/mL Geometric Coefficient of Variation 47	28378 ng*h/mL Geometric Coefficient of Variation 42	26510 ng*h/mL Geometric Coefficient of Variation 40

SECONDARY outcome

Timeframe: On Day 24 or 31

Population: All participants who received at least 1 dose of any study drug.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=64 Participants 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: Atazanavir/Cobicistat FDC n=64 Participants 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: Atazanavir + Cobicistat Coadministered n=64 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Number of Participants Who Died and With Serious Adverse Events (SAEs) Deaths	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Died and With Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

Population: All participants who received at least 1 dose of study drug and had laboratory test results available.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Leukocytes (low)	3 Participants	2 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Neutrophils, absolute (low)	2 Participants	4 Participants	3 Participants	2 Participants	1 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Bilirubin, total (high)	1 Participants	0 Participants	0 Participants	3 Participants	4 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Bilirubin, direct	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Blood, urine (high)	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Red blood cells (RBC), urine (high)	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests White blood cells (WBC), urine (high)	2 Participants	0 Participants	0 Participants	3 Participants	2 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Creatine kinase (high)	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Aspartate aminotransferase (AST) (high)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests Lactate dehydrogenase (high)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

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)

Population: All participants who received at least 1 dose of study medication and were evaluable.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings QT interval >500 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings PR interval >210 msec	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings QRS interval >120 msec	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings QTcF>450 msec	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Time of Maximum Observed Concentration (Tmax) of Atazanavir	3.00 Hours Full Range 39 • Interval 2.0 to 5.5	2.50 Hours Interval 2.0 to 4.05	2.00 Hours Interval 1.0 to 8.0	2.00 Hours Interval 1.0 to 6.0	3.54 Hours Interval 2.0 to 8.02

SECONDARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Observed Concentration at 24 Hours (C24) of Atazanavir	416 ng/mL Geometric Coefficient of Variation 58	449 ng/mL Geometric Coefficient of Variation 52	295 ng/mL Geometric Coefficient of Variation 63	337 ng/mL Geometric Coefficient of Variation 56	398 ng/mL Geometric Coefficient of Variation 45

SECONDARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Apparent Terminal Half-life (T-HALF) of Atazanavir	7.54 Hours Standard Deviation 2.91	7.50 Hours Standard Deviation 2.60	7.25 Hours Standard Deviation 2.49	7.21 Hours Standard Deviation 2.28	7.14 Hours Standard Deviation 2.99

SECONDARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Maximum Observed Plasma Concentration (Cmax) of Cobicistat	1321 ng/mL Geometric Coefficient of Variation 32	1348 ng/mL Geometric Coefficient of Variation 29	952 ng/mL Geometric Coefficient of Variation 39	1033 ng/mL Geometric Coefficient of Variation 38	1060 ng/mL Geometric Coefficient of Variation 32

SECONDARY outcome

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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
Time of Maximum Observed Concentration (Tmax) of Cobicistat	2.52 Hours Interval 1.0 to 5.0	2.52 Hours Interval 1.0 to 5.0	2.00 Hours Interval 1.0 to 5.0	2.00 Hours Interval 1.0 to 5.0	4.00 Hours Interval 1.0 to 12.0

SECONDARY outcome

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)

Population: 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

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.

Outcome measures

Outcome measures
Measure	Treatment A: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=62 Participants 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: Atazanavir + Cobicistat Coadministered n=63 Participants 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: Atazanavir/Cobicistat FDC n=63 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22	Treatment E: Atazanavir/Cobicistat FDC n=30 Participants Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
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 AUC(0-T)	8738 ng*h/mL Geometric Coefficient of Variation 42	8866 ng*h/mL Geometric Coefficient of Variation 38	6541 ng*h/mL Geometric Coefficient of Variation 47	7204 ng*h/mL Geometric Coefficient of Variation 44	7916 ng*h/mL Geometric Coefficient of Variation 39
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 AUC(INF) (n=63, 62, 63, 63, 28)	9045 ng*h/mL Geometric Coefficient of Variation 45	9178 ng*h/mL Geometric Coefficient of Variation 41	7884 ng*h/mL Geometric Coefficient of Variation 45	7408 ng*h/mL Geometric Coefficient of Variation 46	8298 ng*h/mL Geometric Coefficient of Variation 39

SECONDARY outcome

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)

Population: 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.

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.