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

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

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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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.

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

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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.

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. ]

Show Outcome Measure 15

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

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More Information

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