Drug Interaction Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00646776
First received: March 26, 2008
Last updated: January 23, 2013
Last verified: January 2013
Results First Received: September 3, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Antivirals/HIV
Interventions: Drug: Rifabutin
Drug: Rifabutin + Atazanavir + Ritonavir

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    RIB 150 mg Once Daily (QD)     ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly  
STARTED     15 [1]   18 [1]
COMPLETED     14     5  
NOT COMPLETED     1     13  
Adverse Event                 1                 9  
Investigator discretion                 0                 4  
[1] Treated on Day 1



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    RIB 150 mg Once Daily (QD)     ATV/RTV 300/100 mg QD+RIB 150 mg Twice Weekly     Total  
Number of Participants  
[units: participants]
  15     18     33  
Age  
[units: years]
Mean ± Standard Deviation
  36  ± 5     37  ± 9     36  ± 7  
Age, Customized  
[units: participants]
     
<65 years     15     18     33  
>=65 years     0     0     0  
Gender  
[units: participants]
     
Female     2     4     6  
Male     13     14     27  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     5     4     9  
Not Hispanic or Latino     10     14     24  
Unknown or Not Reported     0     0     0  
Race/Ethnicity, Customized [1]
[units: participants]
     
Caucasian     9     5     14  
Black or African American     3     12     15  
Asian     2     0     2  
Other Race     1     1     2  
Body Mass Index (BMI) [2]
[units: kg/m^2]
Mean ± Standard Deviation
  26.1  ± 3.2     26.6  ± 3.5     26.4  ± 3.3  
Height Continuous  
[units: cm]
Mean ± Standard Deviation
  173.7  ± 7.3     174.4  ± 10.0     174.1  ± 8.8  
Weight Continuous  
[units: kg]
Mean ± Standard Deviation
  79.1  ± 12.0     81.3  ± 14.9     80.3  ± 13.5  
[1] Other race comprises American Indian/Alaskan
[2] BMI is defined as the individual's body weight divided by the square of his or her height.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Average Area Under the Plasma Concentration-time Curve for 24 Hours (AUC24avg) for Rifabutin (RIB)   [ 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. ]

2.  Primary:   Maximum Plasma Concentration (Cmax) of 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. ]

3.  Primary:   Minimum Plasma Concentration (Cmin) of 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. ]

4.  Primary:   AUC24avg 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. ]

5.  Primary:   Cmax of 25-O-Desacetylrifabutin (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. ]

6.  Primary:   Cmin of 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. ]

7.  Primary:   Total Area Under the Plasma Concentration-time Curve (AUCtot)   [ 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. ]

8.  Secondary:   Cmax of 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. ]

9.  Secondary:   Cmin of 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. ]

10.  Secondary:   AUC(TAU) 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. ]

11.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) of 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. ]

12.  Secondary:   Terminal Elimination Half-life (T-half) of 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. ]

13.  Secondary:   Cmax of 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. ]

14.  Secondary:   Cmin of 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. ]

15.  Secondary:   AUC(TAU) 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. ]

16.  Secondary:   Tmax of 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. ]

17.  Secondary:   T-half of 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. ]

18.  Secondary:   Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.   [ Time Frame: From Day 1 to 30 days after the last dose of study drug. ]

19.  Secondary:   Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes   [ 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. ]

20.  Secondary:   Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)   [ 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. ]

21.  Secondary:   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)   [ 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. ]

22.  Secondary:   Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)   [ 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. ]

23.  Secondary:   Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)   [ 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. ]

24.  Secondary:   Number of Participants With MAs in Urinalysis   [ Time Frame: Pre-dose on Day -1, Day 7 and discharge. ]

25.  Secondary:   Number of Participants With Identified Electrocardiogram (ECG) Abnormalities   [ Time Frame: Pre-dose on Day -1 and study discharge. ]

26.  Secondary:   Number of Participants With Clinically Significant Vital Signs or Physical Examination Findings   [ Time Frame: Vital signs:screening, prior to dosing on Day 1, Day 7, study discharge. Physical examination:screening, Day -1, Day 7, study discharge ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: ClinicalTrials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00646776     History of Changes
Other Study ID Numbers: AI424-360
Study First Received: March 26, 2008
Results First Received: September 3, 2010
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board