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

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00207090
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arm: 1
• Duration (Months): 38
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to test how rifampin affects the removal of BMS-247550 (ixabepilone) from the body.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors; Neoplasms	Drug: ixabepilone; Drug: Rifampin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Rifampin on the Pharmacokinetics of Ixabepilone in Patients With Advanced Cancer
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixabepilone + rifampin	Drug: ixabepilone; ixabepilone solution, intravenous, 40 mg/m2, once every 3 weeks until disease progression; Other Names: IXEMPRA® BMS-247550 ; Drug: Rifampin; rifampin tablets, oral, 600 mg once daily, only on Days 15 to 21 of Cycle 1 and Days 1 to 7 of Cycle 2

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) [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.]

   Cmax was obtained directly from the concentration-time data.

2. Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF]) [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.]

   AUC (INF) was obtained directly from the concentration-time data.

3. Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half) [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.]

   T half was obtained directly from the concentration-time data.

4. Mean Residence Time Adjusted for Infusion Time (MRT [INF]) [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.]

   (MRT [INF]) was obtained directly from the concentration-time data.

5. Total Body Clearance (CLT) [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.]

   CLT was obtained directly from the concentration-time data.

6. Volume of Distribution at Steady-state (Vss) [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.]

   Vss was obtained directly from the concentration-time data.

7. Time to Reach Maximum Observed Concentration (T Max) [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.]

   T max was obtained directly from the concentration-time data.

8. Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T]) [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.]

   AUC (0-T) was obtained directly from the concentration-time data.

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

   The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.

10. Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22 [Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration.]

    The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.

Secondary Outcome Measures

1. 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 [From Day 1 to 30 days after the last dose of study drug.]

   AEs:new untoward medical occurrences/worsening of pre-existing medical condition,whether or not related to study drug.SAE:AE resulting in death;life threatening;resulted in persistent/significant disability/incapacity;resulted in/prolonged existing hospitalization;a congenital anomaly/birth defect;overdose.Drug-related AEs: relationship to drug of certain;probable;possible;or missing.Participants who discontinued study due to AE were also recorded.AEs graded using National Cancer Institute (NCI) Common Toxicity Criteria (CTC),v3:Grade 1=mild,2=moderate, 3=severe,4=life threatening,5=death.

2. Number of Participants With Grade 3-4 Hematology Abnormalities [Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36.]

   Abnormalities occurring at any time during the study were graded per NCI CTC, v3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are given below. Neutrophils: Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Leukocytes: Grade 3: 1.0 - <2.0x10^9/L, Grade 4: <1.0x10^9/L. Neutrophils + bands (absolute): Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Lymphocytes: Grade 3: 0.2 - <0.5x10^9/L, Grade 4: <0.2x10^9/L. Platelets: Grade 3: 25.0 - <50.0x10^9/L, Grade 4: <25.0x10.

3. Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous [Screening, Days 1 and 22.]

   Abnormalities occurring at any time during the study were graded per the NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows: Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase: Grade 3: >5-20 x upper limit of normal (ULN), Grade 4: >20 x ULN. Bilirubin: Grade 3: >3-10 x ULN, Grade 4: >10 x ULN. Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC). Creatinine: Grade 3: >3-6 x ULN, Grade 4: >6 x ULN. Phosphorous: Grade 3: 1-<2mg/dL, Grade 4: <1mg/dL.

4. Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid. [Screening, Days 2 and 22.]

   Abnormalities occurring at any time during the study were graded per NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows:Calcium: Grade 3: 6-<7 or >12.5-13.5mg/dL, Grade 4:<6 or >13.5mg/dL. Magnesium: Grade 3:0.6-<0.8 or >2.46-6.6mEq/L, Grade 4:<0.6 or >6.6mEq/L. Potassium: Grade 3:2.5-<3 or >6-7mmol/L, Grade 4:<2.5 or >7.0 mmol/L. Sodium: Grade 3:120-<130 or >155-160 mEq/L, Grade 4:<120 or >160mEq/L. Glucose: Grade 3:30-<40 or >250-500mg/dL, Grade 4:<30 or >500mg/dL. Uric acid: Grade 3:>ULN-10mg/dL with physiologic consequences, Grade 4:>10mg/dL.

5. Number of Participants With Clinically Meaningful Vital Signs Measures [From screening to the off treatment visit.]

   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.

6. Number of Participants With Abnormal Physical Examination Findings [From screening to the off treatment visit.]

   Physical examination included height (screening only),weight,BSA,Eastern Cooperative Oncology Group Performance Status (ECOG PS),tendon reflexes,sensory function,motor strength. ECOG PS used to assess disease severity:score of 0 is fully active;1 is restricted physically strenuous activity;2 is ambulatory but unable to work;3 is capable of only limited self care;4 is completely disabled;5 is dead. Normal ranges:height:137-200cm or 54-79 inches;weight:40-135kg or 88-298 pounds (lbs);ECOG Scale:0-4. Abnormalities displayed here are those considered "clinically significant" by the investigator.

7. QT Interval Corrected for Heart Rate (QTcF) [Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion.]

   QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial electrocardiograms (ECGs) that were performed at selected times after the first dose of ixabepilone without rifampin and at matched times prior to the first dose of ixabepilone. Abnormalities occurring at any time during the study were recorded.

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

   Triplicate 12-lead serial ECGs were performed pre-dose (just prior to infusion), 1.5, 3 (just prior to end of the infusion even if infusion lasted for less than or more than planned 3 hrs), 4, 6, 8 and 24 hrs after start of ixabepilone infusion. Triplicate 12-lead serial ECGs were also to be performed on the date prior to dosing at times approximating post-dose schedule (pre-dose triplicate set of ECGs also qualified as the 24-hr baseline ECGs). Normal ranges for ECG are as follows: heart rate: 40 - 125 bpm; PR: 0.1 - 0.2 msec; QRS: 0.06 - 0.12 msec; QTC: 0.3 - 0.45 msec; QT: 0.3 - 0.5 msec.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Up to three prior chemotherapy regimens

• Measurable or non-measurable disease

• Available for treatment and follow-up

Exclusion Criteria:

• Neuropathy

• Uncontrolled cardiovascular disease

• Refusal to participate in genetic analysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• R-Pharm

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00207090
• Other Study ID Numbers: CA163-102
• First Posted: Sep 21, 2005
• Last Update Posted: Nov 2, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Rifampin

Study Results

Participant Flow

Pre-assignment Detail	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)

Arm/Group Title	All Participants
Arm/Group Description	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.
Period Title: Overall Study
STARTED	15
COMPLETED	8
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	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.
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (14)
Age, Customized (participants) [Number]
< 65 years	7 46.7%
>=65 years	8 53.3%
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Race/Ethnicity, Customized (participants) [Number]
White	15 100%
Race/Ethnicity, Customized (participants) [Number]
Not Hispanic/Latino	15 100%
Body surface area (BSA) continuous (square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [square meter]	1.9 (0.3)
Height continuous (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	173.5 (9.0)
Weight continuous (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	80.3 (18.5)

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Description	Cmax was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

Of the 15 patients in each group, only those with evaluable pharmacokinetic (PK) results are presented.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Geometric Mean (90% Confidence Interval) [nanogram (ng)/millilter(mL)]	338.23	308.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixabepilone, Ixabepilone + Rifampin
	Comments	Two-way analyses of variance were performed on log-transformed values of Cmax. The factors in the analyses were participant and day. Point estimates and 90% confidence intervals for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	0.912
	Confidence Interval	(2-Sided) 90%; 0.751 to 1.106
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF])
Description	AUC (INF) was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Geometric Mean (90% Confidence Interval) [nanogram (ng)*hour(hr)/mL]	3028.70	1713.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixabepilone, Ixabepilone + Rifampin
	Comments	Two-way analyses of variance were performed on log-transformed values of (AUC [INF]). The factors in the analyses were participant and day. Point estimates and 90% confidence intervals for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	0.566
	Confidence Interval	(2-Sided) 90%; 0.482 to 0.664
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	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
Description	AEs:new untoward medical occurrences/worsening of pre-existing medical condition,whether or not related to study drug.SAE:AE resulting in death;life threatening;resulted in persistent/significant disability/incapacity;resulted in/prolonged existing hospitalization;a congenital anomaly/birth defect;overdose.Drug-related AEs: relationship to drug of certain;probable;possible;or missing.Participants who discontinued study due to AE were also recorded.AEs graded using National Cancer Institute (NCI) Common Toxicity Criteria (CTC),v3:Grade 1=mild,2=moderate, 3=severe,4=life threatening,5=death.
Time Frame	From Day 1 to 30 days after the last dose of study drug.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Death	0 0%
Other SAEs	4 26.7%
Treatment-related AEs	15 100%
Grade 3-4 AEs	10 66.7%
Discontinuation due to AEs	3 20%

4. Secondary Outcome

Title	Number of Participants With Grade 3-4 Hematology Abnormalities
Description	Abnormalities occurring at any time during the study were graded per NCI CTC, v3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are given below. Neutrophils: Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Leukocytes: Grade 3: 1.0 - <2.0x10^9/L, Grade 4: <1.0x10^9/L. Neutrophils + bands (absolute): Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Lymphocytes: Grade 3: 0.2 - <0.5x10^9/L, Grade 4: <0.2x10^9/L. Platelets: Grade 3: 25.0 - <50.0x10^9/L, Grade 4: <25.0x10.
Time Frame	Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Neutrophils (absolute)	5 33.3%
Leukocytes	6 40%
Neutrophils + bands (absolute)	5 33.3%
Hemoglobin	1 6.7%
Lymphocytes (absolute)	6 40%
Platelet count	0 0%

5. Secondary Outcome

Title	Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Description	Abnormalities occurring at any time during the study were graded per the NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows: Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase: Grade 3: >5-20 x upper limit of normal (ULN), Grade 4: >20 x ULN. Bilirubin: Grade 3: >3-10 x ULN, Grade 4: >10 x ULN. Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC). Creatinine: Grade 3: >3-6 x ULN, Grade 4: >6 x ULN. Phosphorous: Grade 3: 1-<2mg/dL, Grade 4: <1mg/dL.
Time Frame	Screening, Days 1 and 22.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Alanine Aminotransferase	0 0%
Aspartate Aminotransferase	0 0%
Alkaline Phosphatase	0 0%
Bilirubin	0 0%
Albumin	0 0%
Creatinine	0 0%
Phosphorous (inorganic)	1 6.7%

6. Primary Outcome

Title	Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half)
Description	T half was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Mean (Standard Deviation) [Hrs]	50.85 (18.59)	36.45 (15.29)

7. Primary Outcome

Title	Mean Residence Time Adjusted for Infusion Time (MRT [INF])
Description	(MRT [INF]) was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Mean (Standard Deviation) [Hrs]	50.93 (22.05)	29.86 (15.31)

8. Primary Outcome

Title	Total Body Clearance (CLT)
Description	CLT was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Mean (Standard Deviation) [Litres(L)/hr]	28.36 (15.04)	49.99 (17.19)

9. Primary Outcome

Title	Volume of Distribution at Steady-state (Vss)
Description	Vss was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Mean (Standard Deviation) [L]	1323.26 (684.63)	1447.54 (763.15)

10. Primary Outcome

Title	Time to Reach Maximum Observed Concentration (T Max)
Description	T max was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Median (Full Range) [Hrs]	1.57	1.50

11. Secondary Outcome

Title	Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Description	Abnormalities occurring at any time during the study were graded per NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows:Calcium: Grade 3: 6-<7 or >12.5-13.5mg/dL, Grade 4:<6 or >13.5mg/dL. Magnesium: Grade 3:0.6-<0.8 or >2.46-6.6mEq/L, Grade 4:<0.6 or >6.6mEq/L. Potassium: Grade 3:2.5-<3 or >6-7mmol/L, Grade 4:<2.5 or >7.0 mmol/L. Sodium: Grade 3:120-<130 or >155-160 mEq/L, Grade 4:<120 or >160mEq/L. Glucose: Grade 3:30-<40 or >250-500mg/dL, Grade 4:<30 or >500mg/dL. Uric acid: Grade 3:>ULN-10mg/dL with physiologic consequences, Grade 4:>10mg/dL.
Time Frame	Screening, Days 2 and 22.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Calcium (total)	0 0%
Magnesium (serum)	0 0%
Potassium (serum)	0 0%
Sodium (serum)	1 6.7%
Glucose (serum)	0 0%
Uric acid	0 0%

12. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T])
Description	AUC (0-T) was obtained directly from the concentration-time data.
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.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone	Ixabepilone + Rifampin
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. (Participants then proceeded through the rest of Cycle 1 and on to further cycles - see the "ixabepilone + rifampin" treatment arm).	Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. 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.
Measure Participants	14	10
Mean (Standard Deviation) [nanogram (ng)*hr/mL]	3015.45 (1383.85)	1478.31 (486.57)

13. Primary Outcome

Title	Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1
Description	The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.
Time Frame	Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	All Participants
Arm/Group Description	All participants who were enrolled into the study, 24 hours before ixabepilone administration on Day -1. Each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2 on Day 1 of Cycle 1. Each participant was administered an oral dose of 600 mg of rifampin while in a fasted state on Day 22 (Cycle 2). Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23 through 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 2.
Measure Participants	14
0-8 hours	10.04 (5.76)
8-24 hours	9.29 (5.84)

14. Secondary Outcome

Title	Number of Participants With Clinically Meaningful Vital Signs Measures
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.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Number [participants]	0 0%

15. Primary Outcome

Title	Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22
Description	The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.
Time Frame	Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration.

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluable for PK analysis.

Arm/Group Title	Ixabepilone + Rifampin
Arm/Group Description	Each participant was administered an oral dose of 600 mg of rifampin while in a fasted state on Day 22 (Cycle 2). Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2.
Measure Participants	10
0-8 hours	110.88 (101.91)
8-24 hours	62.42 (54.35)

16. Secondary Outcome

Title	Number of Participants With Abnormal Physical Examination Findings
Description	Physical examination included height (screening only),weight,BSA,Eastern Cooperative Oncology Group Performance Status (ECOG PS),tendon reflexes,sensory function,motor strength. ECOG PS used to assess disease severity:score of 0 is fully active;1 is restricted physically strenuous activity;2 is ambulatory but unable to work;3 is capable of only limited self care;4 is completely disabled;5 is dead. Normal ranges:height:137-200cm or 54-79 inches;weight:40-135kg or 88-298 pounds (lbs);ECOG Scale:0-4. Abnormalities displayed here are those considered "clinically significant" by the investigator.
Time Frame	From screening to the off treatment visit.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Weight-related abnormalities	3 20%
Other physical examination abnormalities	0 0%

17. Secondary Outcome

Title	QT Interval Corrected for Heart Rate (QTcF)
Description	QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial electrocardiograms (ECGs) that were performed at selected times after the first dose of ixabepilone without rifampin and at matched times prior to the first dose of ixabepilone. Abnormalities occurring at any time during the study were recorded.
Time Frame	Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion.

Outcome Measure Data

Analysis Population Description

All participants treated with ixabepilone. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Ixabepilone
Arm/Group Description	On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2.
Measure Participants	15
0 hour (n=9)	3.44
1.5 hour (n=14)	5.64
3 hour (n=14)	0.57
4 hour (n=11)	7.82
6 hour (n=13)	6.54
8 hour (n=3)	-10.70
24 hour (n=10)	-1.90

18. Secondary Outcome

Title	Number of Participants With Identified ECG Abnormalities
Description	Triplicate 12-lead serial ECGs were performed pre-dose (just prior to infusion), 1.5, 3 (just prior to end of the infusion even if infusion lasted for less than or more than planned 3 hrs), 4, 6, 8 and 24 hrs after start of ixabepilone infusion. Triplicate 12-lead serial ECGs were also to be performed on the date prior to dosing at times approximating post-dose schedule (pre-dose triplicate set of ECGs also qualified as the 24-hr baseline ECGs). Normal ranges for ECG are as follows: heart rate: 40 - 125 bpm; PR: 0.1 - 0.2 msec; QRS: 0.06 - 0.12 msec; QTC: 0.3 - 0.45 msec; QT: 0.3 - 0.5 msec.
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.

Outcome Measure Data

Analysis Population Description

All participants treated with ixabepilone.

Arm/Group Title	All Participants
Arm/Group Description	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.
Measure Participants	15
Newly identified ECG abnormalities	13 86.7%
Discontinuation due to ECG abnormalities	1 6.7%
Abnormalities related to QT/QTc interval	0 0%
Total number of ECG abnormalities	13 86.7%

Adverse Events

Arm/Group Title	All Participants
Arm/Group Description	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.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
Cardiac disorders
MYOCARDIAL ISCHAEMIA	2/15 (13.3%)
Gastrointestinal disorders
VOMITING	1/15 (6.7%)
General disorders
CHEST PAIN	1/15 (6.7%)
Immune system disorders
HYPERSENSITIVITY	1/15 (6.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN	1/15 (6.7%)
Vascular disorders
HYPERTENSION	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)
Blood and lymphatic system disorders
ANAEMIA	2/15 (13.3%)
LYMPHOPENIA	2/15 (13.3%)
NEUTROPENIA	2/15 (13.3%)
THROMBOCYTOPENIA	1/15 (6.7%)
Eye disorders
PHOTOPHOBIA	1/15 (6.7%)
LACRIMATION INCREASED	1/15 (6.7%)
Gastrointestinal disorders
NAUSEA	6/15 (40%)
RETCHING	1/15 (6.7%)
VOMITING	4/15 (26.7%)
DIARRHOEA	8/15 (53.3%)
DRY MOUTH	1/15 (6.7%)
DYSPHAGIA	1/15 (6.7%)
ORAL PAIN	1/15 (6.7%)
STOMATITIS	2/15 (13.3%)
CONSTIPATION	5/15 (33.3%)
HAEMORRHOIDS	2/15 (13.3%)
ABDOMINAL PAIN	1/15 (6.7%)
General disorders
PAIN	1/15 (6.7%)
CHILLS	6/15 (40%)
FATIGUE	13/15 (86.7%)
FEELING HOT	3/15 (20%)
EARLY SATIETY	1/15 (6.7%)
CHEST DISCOMFORT	1/15 (6.7%)
OEDEMA PERIPHERAL	4/15 (26.7%)
INFUSION SITE PAIN	2/15 (13.3%)
INFUSION SITE WARMTH	1/15 (6.7%)
MUCOSAL INFLAMMATION	2/15 (13.3%)
INJECTION SITE REACTION	2/15 (13.3%)
Hepatobiliary disorders
HEPATOMEGALY	1/15 (6.7%)
Immune system disorders
HYPERSENSITIVITY	1/15 (6.7%)
Infections and infestations
RHINITIS	1/15 (6.7%)
ORAL CANDIDIASIS	1/15 (6.7%)
Injury, poisoning and procedural complications
FALL	1/15 (6.7%)
EXCORIATION	1/15 (6.7%)
Investigations
HAEMOGLOBIN	3/15 (20%)
PLATELET COUNT	1/15 (6.7%)
NEUTROPHIL COUNT	2/15 (13.3%)
WEIGHT DECREASED	3/15 (20%)
HAEMOGLOBIN DECREASED	3/15 (20%)
WHITE BLOOD CELL COUNT	1/15 (6.7%)
PLATELET COUNT DECREASED	3/15 (20%)
NEUTROPHIL COUNT DECREASED	2/15 (13.3%)
WHITE BLOOD CELL COUNT DECREASED	4/15 (26.7%)
WHITE BLOOD CELL COUNT INCREASED	1/15 (6.7%)
ASPARTATE AMINOTRANSFERASE INCREASED	1/15 (6.7%)
Metabolism and nutrition disorders
ANOREXIA	11/15 (73.3%)
HYPOCALCAEMIA	1/15 (6.7%)
HYPERGLYCAEMIA	1/15 (6.7%)
HYPOMAGNESAEMIA	2/15 (13.3%)
HYPOALBUMINAEMIA	2/15 (13.3%)
HYPOPHOSPHATAEMIA	1/15 (6.7%)
DECREASED APPETITE	2/15 (13.3%)
Musculoskeletal and connective tissue disorders
MYALGIA	1/15 (6.7%)
BACK PAIN	4/15 (26.7%)
BONE PAIN	1/15 (6.7%)
NECK PAIN	1/15 (6.7%)
ARTHRALGIA	7/15 (46.7%)
LIMB DISCOMFORT	1/15 (6.7%)
MUSCULAR WEAKNESS	1/15 (6.7%)
PAIN IN EXTREMITY	3/15 (20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN	2/15 (13.3%)
Nervous system disorders
TREMOR	2/15 (13.3%)
HEADACHE	3/15 (20%)
AREFLEXIA	1/15 (6.7%)
DIZZINESS	1/15 (6.7%)
DYSGEUSIA	6/15 (40%)
PARAESTHESIA	1/15 (6.7%)
SENSORY DISTURBANCE	1/15 (6.7%)
NEUROPATHY PERIPHERAL	4/15 (26.7%)
RESTLESS LEGS SYNDROME	1/15 (6.7%)
PERIPHERAL SENSORY NEUROPATHY	3/15 (20%)
Psychiatric disorders
ANXIETY	1/15 (6.7%)
INSOMNIA	2/15 (13.3%)
DEPRESSION	1/15 (6.7%)
RESTLESSNESS	1/15 (6.7%)
Reproductive system and breast disorders
ADNEXA UTERI PAIN	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
COUGH	4/15 (26.7%)
DYSPNOEA	4/15 (26.7%)
HAEMOPTYSIS	1/15 (6.7%)
NASAL CONGESTION	1/15 (6.7%)
DYSPNOEA EXERTIONAL	1/15 (6.7%)
Skin and subcutaneous tissue disorders
RASH	1/15 (6.7%)
ALOPECIA	9/15 (60%)
PRURITUS	2/15 (13.3%)
URTICARIA	1/15 (6.7%)
HYPERHIDROSIS	1/15 (6.7%)
SKIN IRRITATION	1/15 (6.7%)
Vascular disorders
PALLOR	1/15 (6.7%)
FLUSHING	1/15 (6.7%)
HOT FLUSH	1/15 (6.7%)
HYPOTENSION	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.