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Effect of Rifampin on the Pharmacokinetics of Ixabepilone in Patients With Advanced Cancer

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00207090
First received: September 12, 2005
Last updated: October 27, 2010
Last verified: October 2010
History of Changes
Results First Received: September 3, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Advanced Solid Tumors
Neoplasms
Interventions: Drug: ixabepilone
Drug: Rifampin

  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
19 participants were enrolled and 15 were treated with the study drug. 4 participants were not treated (1 participant due to an adverse event [AE] and 3 participants for no longer meeting study criteria)

Reporting Groups
  Description
All Participants All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.

Participant Flow:   Overall Study
    All Participants  
STARTED     15 [1]
COMPLETED     8  
NOT COMPLETED     7  
Study drug toxicity                 3  
Chest wall mass larger                 1  
Disease progression/relapse                 2  
Physician Decision                 1  
[1] Number of participants treated



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
All Participants All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
 		  15  
Age  
[units: years]
Mean ± Standard Deviation 		  62  ± 14  
Age, Customized  
[units: participants]
 		 
< 65 years     7  
>=65 years     8  
Gender  
[units: participants]
 		 
Female     3  
Male     12  
Race/Ethnicity, Customized  
[units: participants]
 		 
White     15  
Race/Ethnicity, Customized  
[units: participants]
 		 
Not Hispanic/Latino     15  
Body surface area (BSA) continuous [1]
[units: square meter]
Mean ± Standard Deviation 		  1.9  ± 0.3  
Height continuous  
[units: centimeter]
Mean ± Standard Deviation 		  173.5  ± 9.0  
Weight continuous  
[units: kilogram]
Mean ± Standard Deviation 		  80.3  ± 18.5  
[1] BSA is the measured or calculated surface of a human body.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Plasma Concentration (Cmax)   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 1

2.  Primary:   Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF])   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 2

3.  Primary:   Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half)   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 3

4.  Primary:   Mean Residence Time Adjusted for Infusion Time (MRT [INF])   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 4

5.  Primary:   Total Body Clearance (CLT)   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 5

6.  Primary:   Volume of Distribution at Steady-state (Vss)   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 6

7.  Primary:   Time to Reach Maximum Observed Concentration (T Max)   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 7

8.  Primary:   Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T])   [ Time Frame: Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 8

9.  Primary:   Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1   [ Time Frame: Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration. ]
  Show Outcome Measure 9

10.  Primary:   Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22   [ Time Frame: Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration. ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants Who Died and Who Experienced Other Serious AEs (SAEs), Grade 3-4 AEs, Drug-related AEs and AEs Leading to Study Drug Discontinuation   [ Time Frame: From Day 1 to 30 days after the last dose of study drug. ]
  Show Outcome Measure 11

12.  Secondary:   Number of Participants With Grade 3-4 Hematology Abnormalities   [ Time Frame: Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36. ]
  Show Outcome Measure 12

13.  Secondary:   Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous   [ Time Frame: Screening, Days 1 and 22. ]
  Show Outcome Measure 13

14.  Secondary:   Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.   [ Time Frame: Screening, Days 2 and 22. ]
  Show Outcome Measure 14

15.  Secondary:   Number of Participants With Clinically Meaningful Vital Signs Measures   [ Time Frame: From screening to the off treatment visit. ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title Number of Participants With Clinically Meaningful Vital Signs Measures
Measure Description Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. Normal ranges for the above are as follows: heart rate: 40 - 125 beats per minute (bpm); systolic BP: 65 - 200 millimeters of mercury (mmHg); diastolic BP: 40 - 120 mmHg; respiratory rate: 10 - 25 breaths per minute; temperature: 95 - 105F or 35 - 40.5C. The abnormalities displayed here are those considered "clinically significant" by the investigator and include abnormalities recorded at any time during study.
Time Frame From screening to the off treatment visit.  
Safety Issue Yes  

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.
All treated participants.

Reporting Groups
  Description
All Participants All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.

Measured Values
    All Participants  
Number of Participants Analyzed  
[units: participants]
 		  15  
Number of Participants With Clinically Meaningful Vital Signs Measures  
[units: participants]
 		  0  

No statistical analysis provided for Number of Participants With Clinically Meaningful Vital Signs Measures



16.  Secondary:   Number of Participants With Abnormal Physical Examination Findings   [ Time Frame: From screening to the off treatment visit. ]
  Show Outcome Measure 16

17.  Secondary:   QT Interval Corrected for Heart Rate (QTcF)   [ Time Frame: Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion. ]
  Show Outcome Measure 17

18.  Secondary:   Number of Participants With Identified ECG Abnormalities   [ Time Frame: Data collected at screening, Day -1 and Day 1 (at 0, 1.5, 3, 4, 6, 8 and 24 hours) after start of infusion. ]
  Show Outcome Measure 18


  Serious Adverse Events
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  Other Adverse Events
  Show Other Adverse Events


  More Information
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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.


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.  


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


No publications provided


Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00207090     History of Changes
Other Study ID Numbers: CA163-102
Study First Received: September 12, 2005
Results First Received: September 3, 2010
Last Updated: October 27, 2010
Health Authority: United States: Food and Drug Administration