Trial Outcomes & Findings for Drug Interaction Study (NCT NCT00646776)
NCT ID: NCT00646776
Last Updated: 2013-01-31
Results Overview
AUC24avg is AUC(0-24 hour) following dosing on Day 10 for RIB 150mg once daily (QD); AUC24avg is the area under the plasma concentration-time curve in 1 dosing interval (AUC\[TAU\]) divided by the number of days over the sampling duration for ATV/RTV 300/100 mg QD+RIB 150 mg twice weekly, i.e. AUC(TAU)/7.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
85 participants
Primary outcome timeframe
Pre-dose (0 hours [h]) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.
Results posted on
2013-01-31
Participant Flow
Of 85 enrolled participants, 52 participants did not receive the study drug (49 did not meet the study criteria and 3 were not needed as study was fully enrolled).
Participant milestones
| Measure |
RIB 150 mg Once Daily (QD)
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
18
|
|
Overall Study
COMPLETED
|
14
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
13
|
Reasons for withdrawal
| Measure |
RIB 150 mg Once Daily (QD)
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
9
|
|
Overall Study
Investigator discretion
|
0
|
4
|
Baseline Characteristics
Drug Interaction Study
Baseline characteristics by cohort
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
36 years
STANDARD_DEVIATION 5 • n=5 Participants
|
37 years
STANDARD_DEVIATION 9 • n=7 Participants
|
36 years
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Age, Customized
<65 years
|
15 participants
n=5 Participants
|
18 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
9 participants
n=5 Participants
|
5 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 participants
n=5 Participants
|
12 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other Race
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
26.1 kg/m^2
STANDARD_DEVIATION 3.2 • n=5 Participants
|
26.6 kg/m^2
STANDARD_DEVIATION 3.5 • n=7 Participants
|
26.4 kg/m^2
STANDARD_DEVIATION 3.3 • n=5 Participants
|
|
Height Continuous
|
173.7 cm
STANDARD_DEVIATION 7.3 • n=5 Participants
|
174.4 cm
STANDARD_DEVIATION 10.0 • n=7 Participants
|
174.1 cm
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Weight Continuous
|
79.1 kg
STANDARD_DEVIATION 12.0 • n=5 Participants
|
81.3 kg
STANDARD_DEVIATION 14.9 • n=7 Participants
|
80.3 kg
STANDARD_DEVIATION 13.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours [h]) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
AUC24avg is AUC(0-24 hour) following dosing on Day 10 for RIB 150mg once daily (QD); AUC24avg is the area under the plasma concentration-time curve in 1 dosing interval (AUC\[TAU\]) divided by the number of days over the sampling duration for ATV/RTV 300/100 mg QD+RIB 150 mg twice weekly, i.e. AUC(TAU)/7.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Average Area Under the Plasma Concentration-time Curve for 24 Hours (AUC24avg) for Rifabutin (RIB)
|
1565 nanograms*hour /milliliters (ng*h/mL)
Full Range 528.49 • Interval 960.1 to 2948.0
|
2311 nanograms*hour /milliliters (ng*h/mL)
Full Range 507.99 • Interval 1738.0 to 3108.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Cmax was derived from plasma concentration versus time for RIB and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of RIB
|
159.0 ng/mL
Full Range 50.52 • Interval 109.3 to 262.0
|
395.6 ng/mL
Full Range 54.32 • Interval 322.0 to 469.3
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Cmin was derived from plasma concentration versus time for RIB.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Minimum Plasma Concentration (Cmin) of RIB
|
28.89 ng/mL
Full Range 14.08 • Interval 16.25 to 67.44
|
40.49 ng/mL
Full Range 11.27 • Interval 29.21 to 61.59
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
AUC24avg is AUC(0-24 hour) following dosing on Day 10 for RIB 150 mg QD; AUC24avg is the area under the plasma concentration-time curve in 1 dosing interval (AUC\[TAU\]) divided by the number of days over the sampling duration for ATV/RTV 300/100 mg QD+RIB 150 mg twice weekly, i.e. AUC(TAU)/7
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
AUC24avg for 25-O-Desacetyl-RIB
|
117.7 ng*h/mL
Full Range 53.48 • Interval 46.0 to 240.7
|
1283 ng*h/mL
Full Range 260.71 • Interval 842.0 to 1634.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Cmax was derived from the plasma concentration versus time for 25-O-Desacetyl-RIB (a metabolite of RIB) and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmax of 25-O-Desacetylrifabutin (25-O-Desacetyl-RIB)
|
13.44 ng/mL
Full Range 4.50 • Interval 7.14 to 22.1
|
104.36 ng/mL
Full Range 21.31 • Interval 64.21 to 128.3
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Cmin was derived from plasma concentration versus time for 25-O-Desacetyl-RIB.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmin of 25-O-Desacetyl-RIB
|
2.79 ng/mL
Full Range 1.40 • Interval 2.03 to 5.42
|
31.97 ng/mL
Full Range 10.60 • Interval 22.13 to 53.44
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (0h) on Days 6, 8, 10, and 11, and post-dose (1h,2h,3h,4h,6h,8h,12h) on Day 10 for RIB 150 mg QD; and pre-dose (0h) on Days 4, 8,11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis. The RIB 300 mg arm represents an extrapolation of the RIB 150 mg arm and as such, does not have a value for "Number of Participants Analyzed". AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
AUCtot represents the total free RIB plus 25-O-Desacetyl-RIB output. It is calculated as: AUCtot (micromolar\[µM\]\*h) = AUC24avg(RIB)(ng\*h/mL)/847.016 (g/mole) + AUC24avg(25-O-Desacetyl-RIB)(ng\*h/mL)/804.979(g/mole). The 300 mg RIB arm represents an extrapolation from the 150 mg RIB group.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=14 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=7 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Total Area Under the Plasma Concentration-time Curve (AUCtot)
|
2.00 µM*h
Full Range 0.68 • Interval 1.19 to 3.77
|
4.38 µM*h
Full Range 0.57 • Interval 3.52 to 5.35
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Cmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmax of ATV
|
5633 ng/mL
Full Range 940.84 • Interval 4110.0 to 7130.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Cmin was derived from the plasma concentration versus time for ATV.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmin of ATV
|
920.69 ng/mL
Full Range 497.07 • Interval 444.0 to 2190.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
AUC(TAU) was derived from the plasma concentration versus time for ATV, and was calculated by linear and log-linear trapezoidal summations using a mixed log-linear algorithm.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
AUC(TAU) for ATV
|
51795 ng*h/mL
Full Range 12680.65 • Interval 37082.0 to 83050.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Tmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV
|
2.00 Hour
Full Range 0.88 • Interval 2.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
T-half was obtained directly from the concentration-time data. T-half following doses administered for treatment ATV/RTV 300/100 mg QD+RIB 150 mg twice weekly.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Terminal Elimination Half-life (T-half) of ATV
|
11.89 Hour
Standard Deviation 3.65 • Interval 7.58 to 18.98
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Cmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmax of RTV
|
1466 ng/mL
Full Range 467.23 • Interval 830.0 to 2200.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Cmin was derived from the plasma concentration versus time for RTV.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Cmin of RTV
|
40.54 ng/mL
Full Range 34.78 • Interval 20.8 to 130.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
AUC(TAU) was derived from the plasma concentration versus time for RTV, and was calculated by linear and log-linear trapezoidal summations using a mixed log-linear algorithm.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
AUC(TAU) for RTV
|
8699 ng*h/mL
Full Range 3002.89 • Interval 5619.0 to 12999.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Tmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Tmax of RTV
|
4.00 Hour
Full Range 0.87 • Interval 3.0 to 6.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.Population: All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
T-half was obtained directly from the concentration-time data.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=9 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
T-half of RTV
|
4.45 Hour
Standard Deviation 0.65 • Interval 3.52 to 5.66
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 to 30 days after the last dose of study drug.Population: All treated participants.
AEs were defined as new, untoward medical occurrences/worsening of pre-existing medical condition, whether drug-related or not. SAEs were defined as any AE that: resulted in death; was life threatening; resulted in a persistent or significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was a cancer; or was an overdose. Discontinuation from the study was due either to an AE or was conducted at the investigator's discretion.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
Deaths
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
Other SAEs
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
AEs
|
5 Participants
|
13 Participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
AE leading to discontinuation
|
1 Participants
|
9 Participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
Discontinuation due to investigator discretion
|
0 Participants
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.Population: All treated participants. If a value had "not evaluable" in the dataset, then these participants were not counted (hemoglobin and hematocrit).
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin/hematocrit: \<0.85 x pre-treatment (pre-Rx) value. Platelet count: \<0.85 x lower limit of normal (LLN) (or, if pre-Rx value \<LLN, then \<0.85 x pre-Rx value) or \>1.5 x upper limit of normal (ULN). Leukocytes: \<0.9 x LLN or \>1.2 x ULN (or, if pre-Rx value \<LLN, then \<0.85 x pre-Rx or \>ULN. If pre-Rx value \>ULN, then \>1.15 x pre-Rx or \<LLN).
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes
Hemoglobin
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes
Hematocrit
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes
Platelet count
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes
Leukocytes
|
1 Participants
|
7 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.Population: All treated participants. If a value had "not evaluable" in the dataset, then these participants were not counted(neutrophils + bands \[absolute\], monocytes \[absolute\], basophils \[absolute\] and eosinophils \[absolute\]).
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Neutrophils+bands (absolute): \<=1.50 x 10\^3 cells/microliter (uL). Lymphocytes (absolute): \<0.75 x 10\^3 cells/uL or \>7.50 x 10\^3 cells/uL. Monocytes (absolute): \>2.00 x 10\^3 cells/uL. Basophils (absolute): \>0.40 x 10\^3 cells/uL. Eosinophils (absolute): \>0.75 x 10\^3 cells/uL.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Neutrophils+bands (absolute)
|
1 Participants
|
10 Participants
|
—
|
|
Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Lymphocytes (absolute)
|
1 Participants
|
5 Participants
|
—
|
|
Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Monocytes (absolute)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Basophils (absolute)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Eosinophils (absolute)
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.Population: All treated participants. If a value had "not evaluable" in the dataset, then these participants were not counted (ALP, AST, ALT, bilirubin \[total\], bilirubin \[direct\], BUN and creatinine).
MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, AST, ALT:\>1.25xULN (if pre-Rx \>ULN, then \>1.25xpre-Rx). Bilirubin (total), bilirubin (direct), BUN:\>1.1xULN (if pre-Rx \>ULN, then \>1.25xpre-Rx). Creatinine:\>1.33xpre-Rx. Sodium (serum):\<0.95xLLN or \>1.05xULN (if pre-Rx \<LLN, then \<0.95xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.05xpre-Rx or \<LLN). Potassium (serum):\<0.9xLLN or \>1.1xULN (if pre-Rx \<LLN, then \<0.9xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1xpre-Rx or \<LLN).
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
ALP
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
AST
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
ALT
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
Bilirubin (total)
|
0 Participants
|
17 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
Bilirubin (direct)
|
0 Participants
|
16 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
BUN
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
Creatinine
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
Sodium (serum)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)
Potassium (serum)
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.Population: All treated participants.
MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. Chloride (serum), calcium (total), protein (total):\<0.9xLLN or \>1.1xULN (if pre-Rx \<LLN, then \<0.9xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1xpre-Rx or \<LLN). Bicarbonate:\<0.8xLLN or \>1.2xULN (if pre-Rx value \<LLN, then \<0.8xpre-Rx value or \>ULN. If pre-Rx \>ULN, then \>1.2xpre-Rx value or \<ULN). Phosphorous (inorganic):\<0.85xLLN or \>1.25xULN (if pre-Rx \<ULN, then \<0.85xpre-Rx or \<ULN. If pre-Rx \>ULN, then \>1.25x re-Rx or \<LLN).
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Chloride (serum)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Calcium (total)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Protein (total)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Bicarbonate
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Phosphorous (inorganic)
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.Population: All treated participants. If a value had "not evaluable" in the dataset, then these participants were not counted(albumin, creatine kinase, uric acid and LDH).
MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. Glucose (fasting serum): \<0.8 x LLN or \>1.5 ULN (if pre-Rx \<LLN, then \<0.8 x pre-Rx or \>ULN. If pre-Rx \>ULN, then \>2.0 x pre-Rx or \<LLN. Albumin: \<0.9 x LLN (if pre-Rx \<LLN, then \<0.9 x pre-Rx). Creatine kinase: \>1.5 x ULN (if pre-Rx \>ULN, then \>1.5 x pre-Rx). Uric acid: \>1.2 x ULN (if pre-Rx \>ULN, then \>1.25 x pre-Rx). LDH: \>1.25 x ULN (if pre-Rx \>ULN, then \>1.5 x pre-Rx).
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
Glucose (Fasting Serum)
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
Albumin
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
Creatine Kinase
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
Uric Acid
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
LDH
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1, Day 7 and discharge.Population: All participants who received the study drug on Day 1 were included in the analysis. If a value had "not evaluable" in the dataset, then these participants were not counted (for all parameters: protein, glucose and blood).
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs. Protein, glucose and blood: \>=2+ (or, if pre-treatment value \>=1+, then \>= 2 x pre-treatment value).
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With MAs in Urinalysis
Protein
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With MAs in Urinalysis
Glucose
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With MAs in Urinalysis
Blood
|
0 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Day -1 and study discharge.Population: All participants who received the study drug on Day 1 were included in the analysis.
ECG abnormalities were defined as findings that are clinically meaningful as judged by the investigator. A 12-lead ECG was recorded at least 5 minutes after the participant had been lying down and all ECG recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
|
0 Participants
|
3 Participants
|
—
|
SECONDARY outcome
Timeframe: Vital signs:screening, prior to dosing on Day 1, Day 7, study discharge. Physical examination:screening, Day -1, Day 7, study dischargePopulation: All treated participants.
Vital signs assessments and physical examination were conducted throughout the study. Vital signs assessments included body temperature, respiratory rate, blood pressure (systolic and diastolic), and heart rate. Physical examination included a neurological examination (if ocular signs or symptoms occurred, a reflex to slit lamp exam was performed by an ophthalmologist). The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs or physical examination were clinically meaningful.
Outcome measures
| Measure |
RIB 150 mg Once Daily (QD)
n=15 Participants
Participants were administered an oral dose of rifabutin (RIB) 150 mg QD on Days 1 to 10. RIB was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
n=18 Participants
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QD on Days 1 to 17 and an oral dose of RIB 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Study treatment was given in the morning within 5 minutes of completing a light meal. Participants were admitted to the clinical facility the evening prior to dosing (Day -1) and remained confined for the duration of the study.
|
RIB 300 mg QD
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Vital Signs or Physical Examination Findings
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
ATV/RTV 300/100mg+RIB 150mg
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
RIB 150mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ATV/RTV 300/100mg+RIB 150mg
n=18 participants at risk
|
RIB 150mg
n=15 participants at risk
|
|---|---|---|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
11.1%
2/18
|
0.00%
0/15
|
Other adverse events
| Measure |
ATV/RTV 300/100mg+RIB 150mg
n=18 participants at risk
|
RIB 150mg
n=15 participants at risk
|
|---|---|---|
|
Cardiac disorders
PALPITATIONS
|
5.6%
1/18
|
0.00%
0/15
|
|
Cardiac disorders
VENTRICULAR EXTRASYSTOLES
|
5.6%
1/18
|
0.00%
0/15
|
|
Eye disorders
EYE PAIN
|
5.6%
1/18
|
0.00%
0/15
|
|
Eye disorders
EYE PRURITUS
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
11.1%
2/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
DIARRHOEA
|
22.2%
4/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
DRY MOUTH
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
FREQUENT BOWEL MOVEMENTS
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
GINGIVAL PAIN
|
0.00%
0/18
|
6.7%
1/15
|
|
Gastrointestinal disorders
LIP SWELLING
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
MOUTH ULCERATION
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
NAUSEA
|
5.6%
1/18
|
6.7%
1/15
|
|
Gastrointestinal disorders
SWOLLEN TONGUE
|
5.6%
1/18
|
0.00%
0/15
|
|
Gastrointestinal disorders
VOMITING
|
5.6%
1/18
|
6.7%
1/15
|
|
General disorders
CHEST DISCOMFORT
|
5.6%
1/18
|
0.00%
0/15
|
|
General disorders
CHEST PAIN
|
5.6%
1/18
|
0.00%
0/15
|
|
General disorders
CHILLS
|
11.1%
2/18
|
6.7%
1/15
|
|
General disorders
FATIGUE
|
5.6%
1/18
|
0.00%
0/15
|
|
General disorders
FEELING COLD
|
5.6%
1/18
|
0.00%
0/15
|
|
General disorders
PAIN
|
16.7%
3/18
|
6.7%
1/15
|
|
General disorders
PYREXIA
|
33.3%
6/18
|
6.7%
1/15
|
|
Hepatobiliary disorders
JAUNDICE
|
16.7%
3/18
|
0.00%
0/15
|
|
Infections and infestations
CELLULITIS
|
5.6%
1/18
|
0.00%
0/15
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
27.8%
5/18
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
0.00%
0/18
|
13.3%
2/15
|
|
Nervous system disorders
DIZZINESS
|
16.7%
3/18
|
0.00%
0/15
|
|
Nervous system disorders
HEADACHE
|
16.7%
3/18
|
13.3%
2/15
|
|
Nervous system disorders
HYPOAESTHESIA
|
5.6%
1/18
|
0.00%
0/15
|
|
Psychiatric disorders
SLEEP DISORDER
|
5.6%
1/18
|
0.00%
0/15
|
|
Renal and urinary disorders
POLLAKIURIA
|
11.1%
2/18
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
CHOKING SENSATION
|
5.6%
1/18
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
5.6%
1/18
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
5.6%
1/18
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGEAL OEDEMA
|
5.6%
1/18
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
|
0.00%
0/18
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
THROAT IRRITATION
|
5.6%
1/18
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
THROAT TIGHTNESS
|
11.1%
2/18
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
0.00%
0/18
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
RASH
|
5.6%
1/18
|
13.3%
2/15
|
|
Vascular disorders
FLUSHING
|
5.6%
1/18
|
0.00%
0/15
|
|
Vascular disorders
HOT FLUSH
|
5.6%
1/18
|
0.00%
0/15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER