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Drug Interaction Study

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ClinicalTrials.gov Identifier: NCT00646776
Recruitment Status : Completed
First Posted : March 31, 2008
Results First Posted : January 5, 2011
Last Update Posted : January 31, 2013
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Antivirals/HIV
Interventions Drug: Rifabutin
Drug: Rifabutin + Atazanavir + Ritonavir
Enrollment 85
Recruitment Details  
Pre-assignment Details 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).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 15 [1] 18 [1]
Completed 14 5
Not Completed 1 13
Reason Not Completed
Adverse Event             1             9
Investigator discretion             0             4
[1]
Treated on Day 1
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 15 18 33
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 18 participants 33 participants
36  (5) 37  (9) 36  (7)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
<65 years 15 18 33
>=65 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Female
2
  13.3%
4
  22.2%
6
  18.2%
Male
13
  86.7%
14
  77.8%
27
  81.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Hispanic or Latino
5
  33.3%
4
  22.2%
9
  27.3%
Not Hispanic or Latino
10
  66.7%
14
  77.8%
24
  72.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Caucasian 9 5 14
Black or African American 3 12 15
Asian 2 0 2
Other Race 1 1 2
[1]
Measure Description: Other race comprises American Indian/Alaskan
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 15 participants 18 participants 33 participants
26.1  (3.2) 26.6  (3.5) 26.4  (3.3)
[1]
Measure Description: BMI is defined as the individual's body weight divided by the square of his or her height.
Height Continuous  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 15 participants 18 participants 33 participants
173.7  (7.3) 174.4  (10.0) 174.1  (8.8)
Weight Continuous  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 15 participants 18 participants 33 participants
79.1  (12.0) 81.3  (14.9) 80.3  (13.5)
1.Primary Outcome
Title Average Area Under the Plasma Concentration-time Curve for 24 Hours (AUC24avg) for Rifabutin (RIB)
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: nanograms*hour /milliliters (ng*h/mL)
1565
(960.1 to 2948)
2311
(1738 to 3108)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 1.477
Confidence Interval (2-Sided) 90%
1.188 to 1.835
Estimation Comments Point estimates and 90% confidence intervals of treatment differences on the log scale were exponentiated to obtain estimates on the original scale.
2.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of RIB
Hide Description Cmax was derived from plasma concentration versus time for RIB and was recorded directly from experimental observations for each treatment period.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: ng/mL
159.0
(109.3 to 262.0)
395.6
(322.0 to 469.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 2.489
Confidence Interval (2-Sided) 90%
2.025 to 3.060
Estimation Comments Point estimates and 90% confidence intervals of treatment differences on the log scale were exponentiated to obtain estimates on the original scale.
3.Primary Outcome
Title Minimum Plasma Concentration (Cmin) of RIB
Hide Description Cmin was derived from plasma concentration versus time for RIB.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: ng/mL
28.89
(16.25 to 67.44)
40.49
(29.21 to 61.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 1.402
Confidence Interval (2-Sided) 90%
1.052 to 1.867
Estimation Comments Point estimates and 90% confidence intervals of treatment differences on the log scale were exponentiated to obtain estimates on the original scale.
4.Primary Outcome
Title AUC24avg for 25-O-Desacetyl-RIB
Hide Description 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
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: ng*h/mL
117.7
(46.0 to 240.7)
1283
(842.0 to 1634)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 10.902
Confidence Interval (2-Sided) 90%
8.135 to 14.610
Estimation Comments [Not Specified]
5.Primary Outcome
Title Cmax of 25-O-Desacetylrifabutin (25-O-Desacetyl-RIB)
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: ng/mL
13.44
(7.14 to 22.10)
104.36
(64.21 to 128.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 7.766
Confidence Interval (2-Sided) 90%
6.133 to 9.833
Estimation Comments [Not Specified]
6.Primary Outcome
Title Cmin of 25-O-Desacetyl-RIB
Hide Description Cmin was derived from plasma concentration versus time for 25-O-Desacetyl-RIB.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RIB as specified per protocol, and were evaluable for analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 14 7
Geometric Mean (Full Range)
Unit of Measure: ng/mL
2.79
(2.03 to 5.42)
31.97
(22.13 to 53.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 11.451
Confidence Interval (2-Sided) 90%
8.147 to 16.095
Estimation Comments [Not Specified]
7.Primary Outcome
Title Total Area Under the Plasma Concentration-time Curve (AUCtot)
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly RIB 300 mg QD
Hide Arm/Group Description:
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.
Participants were administered an oral dose of atazanavir/ritonavir (ATV/RTV) 300/100 mg QAD 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.
AUCtot for RIB 300 mg QD was calculated as 2 × AUCtot for RIB 150 mg QD.
Overall Number of Participants Analyzed 14 7 0
Geometric Mean (Full Range)
Unit of Measure: µM*h
2.00
(1.19 to 3.77)
4.38
(3.52 to 5.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RIB 150 mg Once Daily (QD), ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 2.190
Confidence Interval (2-Sided) 90%
1.783 to 2.691
Estimation Comments Point estimates and 90% confidence intervals of treatment differences on the log scale were exponentiated to obtain estimates on the original scale.
8.Secondary Outcome
Title Cmax of ATV
Hide Description Cmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng/mL
5633
(4110 to 7130)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.947
Confidence Interval (2-Sided) 90%
0.817 to 1.098
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Cmin of ATV
Hide Description Cmin was derived from the plasma concentration versus time for ATV.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng/mL
920.69
(444.00 to 2190.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0963
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.7450
Confidence Interval (2-Sided) 90%
0.5569 to 0.9967
Estimation Comments [Not Specified]
10.Secondary Outcome
Title AUC(TAU) for ATV
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng*h/mL
51795
(37082 to 83050)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.857
Confidence Interval (2-Sided) 90%
0.723 to 1.015
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV
Hide Description Tmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: Hour
2.00
(2.00 to 4.00)
12.Secondary Outcome
Title Terminal Elimination Half-life (T-half) of ATV
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of ATV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: Hour
11.89  (3.65)
13.Secondary Outcome
Title Cmax of RTV
Hide Description Cmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng/mL
1466
(830.0 to 2200)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.660
Confidence Interval (2-Sided) 90%
0.538 to 0.809
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Cmin of RTV
Hide Description Cmin was derived from the plasma concentration versus time for RTV.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng/mL
40.54
(20.80 to 130.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.651
Confidence Interval (2-Sided) 90%
0.430 to 0.986
Estimation Comments [Not Specified]
15.Secondary Outcome
Title AUC(TAU) for RTV
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Geometric Mean (Full Range)
Unit of Measure: ng*h/mL
8699
(5619 to 12999)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.696
Confidence Interval (2-Sided) 90%
0.563 to 0.862
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Tmax of RTV
Hide Description Tmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: Hour
4.00
(3.00 to 6.00)
17.Secondary Outcome
Title T-half of RTV
Hide Description T-half was obtained directly from the concentration-time data.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received all doses of RTV as specified per protocol, and were evaluable for analysis.
Arm/Group Title ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
Participants were randomized to receive Atazanavir/Ritonavir 300/100mg orally once daily on Days 1 to 17. Participants also received oral dose of Rifabutin 150 mg twice weekly on Days 1, 4, 8, 11 and 15. Participants were dosed 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 Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: Hour
4.45  (0.65)
18.Secondary Outcome
Title Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.
Hide Description 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.
Time Frame From Day 1 to 30 days after the last dose of study drug.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Deaths 0 0
Other SAEs 0 2
AEs 5 13
AE leading to discontinuation 1 9
Discontinuation due to investigator discretion 0 4
19.Secondary Outcome
Title Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes
Hide Description 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).
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants. If a value had "not evaluable" in the dataset, then these participants were not counted (hemoglobin and hematocrit).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Hemoglobin 0 1
Hematocrit 0 1
Platelet count 0 0
Leukocytes 1 7
20.Secondary Outcome
Title Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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]).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Neutrophils+bands (absolute) 1 10
Lymphocytes (absolute) 1 5
Monocytes (absolute) 0 0
Basophils (absolute) 0 0
Eosinophils (absolute) 0 0
21.Secondary Outcome
Title 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)
Hide Description 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).
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
ALP 0 0
AST 0 0
ALT 0 0
Bilirubin (total) 0 17
Bilirubin (direct) 0 16
BUN 0 0
Creatinine 0 1
Sodium (serum) 0 0
Potassium (serum) 0 0
22.Secondary Outcome
Title Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)
Hide Description 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).
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Chloride (serum) 0 0
Calcium (total) 0 0
Protein (total) 0 0
Bicarbonate 0 0
Phosphorous (inorganic) 0 0
23.Secondary Outcome
Title Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)
Hide Description 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).
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Glucose (Fasting Serum) 0 0
Albumin 0 0
Creatine Kinase 0 0
Uric Acid 0 0
LDH 0 0
24.Secondary Outcome
Title Number of Participants With MAs in Urinalysis
Hide Description 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).
Time Frame Pre-dose on Day -1, Day 7 and discharge.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
Protein 0 1
Glucose 0 0
Blood 0 1
25.Secondary Outcome
Title Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
Hide Description 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.
Time Frame Pre-dose on Day -1 and study discharge.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study drug on Day 1 were included in the analysis.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
0 3
26.Secondary Outcome
Title Number of Participants With Clinically Significant Vital Signs or Physical Examination Findings
Hide Description 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.
Time Frame Vital signs:screening, prior to dosing on Day 1, Day 7, study discharge. Physical examination:screening, Day -1, Day 7, study discharge
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title RIB 150 mg Once Daily (QD) ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: Participants
0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ATV/RTV 300/100mg+RIB 150mg RIB 150mg
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
ATV/RTV 300/100mg+RIB 150mg RIB 150mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ATV/RTV 300/100mg+RIB 150mg RIB 150mg
Affected / at Risk (%) Affected / at Risk (%)
Total   2/18 (11.11%)   0/15 (0.00%) 
Investigations     
NEUTROPHIL COUNT DECREASED  1  2/18 (11.11%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ATV/RTV 300/100mg+RIB 150mg RIB 150mg
Affected / at Risk (%) Affected / at Risk (%)
Total   13/18 (72.22%)   5/15 (33.33%) 
Cardiac disorders     
PALPITATIONS  1  1/18 (5.56%)  0/15 (0.00%) 
VENTRICULAR EXTRASYSTOLES  1  1/18 (5.56%)  0/15 (0.00%) 
Eye disorders     
EYE PAIN  1  1/18 (5.56%)  0/15 (0.00%) 
EYE PRURITUS  1  1/18 (5.56%)  0/15 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION  1  1/18 (5.56%)  0/15 (0.00%) 
ABDOMINAL PAIN  1  2/18 (11.11%)  0/15 (0.00%) 
ABDOMINAL PAIN UPPER  1  1/18 (5.56%)  0/15 (0.00%) 
DIARRHOEA  1  4/18 (22.22%)  0/15 (0.00%) 
DRY MOUTH  1  1/18 (5.56%)  0/15 (0.00%) 
FREQUENT BOWEL MOVEMENTS  1  1/18 (5.56%)  0/15 (0.00%) 
GINGIVAL PAIN  1  0/18 (0.00%)  1/15 (6.67%) 
LIP SWELLING  1  1/18 (5.56%)  0/15 (0.00%) 
MOUTH ULCERATION  1  1/18 (5.56%)  0/15 (0.00%) 
NAUSEA  1  1/18 (5.56%)  1/15 (6.67%) 
SWOLLEN TONGUE  1  1/18 (5.56%)  0/15 (0.00%) 
VOMITING  1  1/18 (5.56%)  1/15 (6.67%) 
General disorders     
CHEST DISCOMFORT  1  1/18 (5.56%)  0/15 (0.00%) 
CHEST PAIN  1  1/18 (5.56%)  0/15 (0.00%) 
CHILLS  1  2/18 (11.11%)  1/15 (6.67%) 
FATIGUE  1  1/18 (5.56%)  0/15 (0.00%) 
FEELING COLD  1  1/18 (5.56%)  0/15 (0.00%) 
PAIN  1  3/18 (16.67%)  1/15 (6.67%) 
PYREXIA  1  6/18 (33.33%)  1/15 (6.67%) 
Hepatobiliary disorders     
JAUNDICE  1  3/18 (16.67%)  0/15 (0.00%) 
Infections and infestations     
CELLULITIS  1  1/18 (5.56%)  0/15 (0.00%) 
Investigations     
NEUTROPHIL COUNT DECREASED  1  5/18 (27.78%)  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders     
PAIN IN JAW  1  0/18 (0.00%)  2/15 (13.33%) 
Nervous system disorders     
DIZZINESS  1  3/18 (16.67%)  0/15 (0.00%) 
HEADACHE  1  3/18 (16.67%)  2/15 (13.33%) 
HYPOAESTHESIA  1  1/18 (5.56%)  0/15 (0.00%) 
Psychiatric disorders     
SLEEP DISORDER  1  1/18 (5.56%)  0/15 (0.00%) 
Renal and urinary disorders     
POLLAKIURIA  1  2/18 (11.11%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
CHOKING SENSATION  1  1/18 (5.56%)  0/15 (0.00%) 
COUGH  1  1/18 (5.56%)  1/15 (6.67%) 
NASAL CONGESTION  1  1/18 (5.56%)  0/15 (0.00%) 
PHARYNGEAL OEDEMA  1  1/18 (5.56%)  0/15 (0.00%) 
PHARYNGOLARYNGEAL PAIN  1  0/18 (0.00%)  1/15 (6.67%) 
THROAT IRRITATION  1  1/18 (5.56%)  0/15 (0.00%) 
THROAT TIGHTNESS  1  2/18 (11.11%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders     
ERYTHEMA  1  0/18 (0.00%)  1/15 (6.67%) 
RASH  1  1/18 (5.56%)  2/15 (13.33%) 
Vascular disorders     
FLUSHING  1  1/18 (5.56%)  0/15 (0.00%) 
HOT FLUSH  1  1/18 (5.56%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00646776     History of Changes
Other Study ID Numbers: AI424-360
First Submitted: March 26, 2008
First Posted: March 31, 2008
Results First Submitted: September 3, 2010
Results First Posted: January 5, 2011
Last Update Posted: January 31, 2013