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)
19
Enrollment
1
Location
1
Arm
38
Duration (Months)
0.5
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1The Cleveland Clinic FoundationClevelandOhioUnited States44195

    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.
    Responsible Party:
    , ,
    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail19 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 TitleAll Participants
    Arm/Group DescriptionAll 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
    STARTED15
    COMPLETED8
    NOT COMPLETED7

    Baseline Characteristics

    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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
    TitleMaximum Plasma Concentration (Cmax)
    DescriptionCmax was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterPoint estimate
    Estimated Value0.912
    Confidence Interval (2-Sided) 90%
    0.751 to 1.106
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF])
    DescriptionAUC (INF) was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterPoint estimate
    Estimated Value0.566
    Confidence Interval (2-Sided) 90%
    0.482 to 0.664
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    TitleNumber 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
    DescriptionAEs: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 FrameFrom Day 1 to 30 days after the last dose of study drug.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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
    TitleNumber of Participants With Grade 3-4 Hematology Abnormalities
    DescriptionAbnormalities 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 FrameScreening, Day 1, Day 8, Day 15, Day 22 and Day 29-36.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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
    TitleNumber of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
    DescriptionAbnormalities 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 FrameScreening, Days 1 and 22.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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
    TitleTime Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half)
    DescriptionT half was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Mean (Standard Deviation) [Hrs]
    50.85
    (18.59)
    36.45
    (15.29)
    7. Primary Outcome
    TitleMean Residence Time Adjusted for Infusion Time (MRT [INF])
    Description(MRT [INF]) was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Mean (Standard Deviation) [Hrs]
    50.93
    (22.05)
    29.86
    (15.31)
    8. Primary Outcome
    TitleTotal Body Clearance (CLT)
    DescriptionCLT was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Mean (Standard Deviation) [Litres(L)/hr]
    28.36
    (15.04)
    49.99
    (17.19)
    9. Primary Outcome
    TitleVolume of Distribution at Steady-state (Vss)
    DescriptionVss was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Mean (Standard Deviation) [L]
    1323.26
    (684.63)
    1447.54
    (763.15)
    10. Primary Outcome
    TitleTime to Reach Maximum Observed Concentration (T Max)
    DescriptionT max was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Median (Full Range) [Hrs]
    1.57
    1.50
    11. Secondary Outcome
    TitleNumber of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
    DescriptionAbnormalities 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 FrameScreening, Days 2 and 22.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T])
    DescriptionAUC (0-T) was obtained directly from the concentration-time data.
    Time FrameBlood 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 TitleIxabepiloneIxabepilone + Rifampin
    Arm/Group DescriptionOn 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 Participants1410
    Mean (Standard Deviation) [nanogram (ng)*hr/mL]
    3015.45
    (1383.85)
    1478.31
    (486.57)
    13. Primary Outcome
    TitleUrine 6B-Hydroxycortisol to Cortisol Ratio on Day -1
    DescriptionThe 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 FrameDay -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 TitleAll Participants
    Arm/Group DescriptionAll 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 Participants14
    0-8 hours
    10.04
    (5.76)
    8-24 hours
    9.29
    (5.84)
    14. Secondary Outcome
    TitleNumber of Participants With Clinically Meaningful Vital Signs Measures
    DescriptionVital 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 FrameFrom screening to the off treatment visit.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    Number [participants]
    0
    0%
    15. Primary Outcome
    TitleUrine 6B-Hydroxycortisol to Cortisol Ratio on Day 22
    DescriptionThe 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 FrameDay 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 TitleIxabepilone + Rifampin
    Arm/Group DescriptionEach 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 Participants10
    0-8 hours
    110.88
    (101.91)
    8-24 hours
    62.42
    (54.35)
    16. Secondary Outcome
    TitleNumber of Participants With Abnormal Physical Examination Findings
    DescriptionPhysical 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 FrameFrom screening to the off treatment visit.

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    Weight-related abnormalities
    3
    20%
    Other physical examination abnormalities
    0
    0%
    17. Secondary Outcome
    TitleQT Interval Corrected for Heart Rate (QTcF)
    DescriptionQT 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 FrameData 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 TitleIxabepilone
    Arm/Group DescriptionOn Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2.
    Measure Participants15
    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
    TitleNumber of Participants With Identified ECG Abnormalities
    DescriptionTriplicate 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 FrameData 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 TitleAll Participants
    Arm/Group DescriptionAll 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 Participants15
    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

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll 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
    Total4/15 (26.7%)
    Cardiac disorders
    MYOCARDIAL ISCHAEMIA2/15 (13.3%)
    Gastrointestinal disorders
    VOMITING1/15 (6.7%)
    General disorders
    CHEST PAIN1/15 (6.7%)
    Immune system disorders
    HYPERSENSITIVITY1/15 (6.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR PAIN1/15 (6.7%)
    Vascular disorders
    HYPERTENSION1/15 (6.7%)
    Other (Not Including Serious) Adverse Events
    All Participants
    Affected / at Risk (%)# Events
    Total14/15 (93.3%)
    Blood and lymphatic system disorders
    ANAEMIA2/15 (13.3%)
    LYMPHOPENIA2/15 (13.3%)
    NEUTROPENIA2/15 (13.3%)
    THROMBOCYTOPENIA1/15 (6.7%)
    Eye disorders
    PHOTOPHOBIA1/15 (6.7%)
    LACRIMATION INCREASED1/15 (6.7%)
    Gastrointestinal disorders
    NAUSEA6/15 (40%)
    RETCHING1/15 (6.7%)
    VOMITING4/15 (26.7%)
    DIARRHOEA8/15 (53.3%)
    DRY MOUTH1/15 (6.7%)
    DYSPHAGIA1/15 (6.7%)
    ORAL PAIN1/15 (6.7%)
    STOMATITIS2/15 (13.3%)
    CONSTIPATION5/15 (33.3%)
    HAEMORRHOIDS2/15 (13.3%)
    ABDOMINAL PAIN1/15 (6.7%)
    General disorders
    PAIN1/15 (6.7%)
    CHILLS6/15 (40%)
    FATIGUE13/15 (86.7%)
    FEELING HOT3/15 (20%)
    EARLY SATIETY1/15 (6.7%)
    CHEST DISCOMFORT1/15 (6.7%)
    OEDEMA PERIPHERAL4/15 (26.7%)
    INFUSION SITE PAIN2/15 (13.3%)
    INFUSION SITE WARMTH1/15 (6.7%)
    MUCOSAL INFLAMMATION2/15 (13.3%)
    INJECTION SITE REACTION2/15 (13.3%)
    Hepatobiliary disorders
    HEPATOMEGALY1/15 (6.7%)
    Immune system disorders
    HYPERSENSITIVITY1/15 (6.7%)
    Infections and infestations
    RHINITIS1/15 (6.7%)
    ORAL CANDIDIASIS1/15 (6.7%)
    Injury, poisoning and procedural complications
    FALL1/15 (6.7%)
    EXCORIATION1/15 (6.7%)
    Investigations
    HAEMOGLOBIN3/15 (20%)
    PLATELET COUNT1/15 (6.7%)
    NEUTROPHIL COUNT2/15 (13.3%)
    WEIGHT DECREASED3/15 (20%)
    HAEMOGLOBIN DECREASED3/15 (20%)
    WHITE BLOOD CELL COUNT1/15 (6.7%)
    PLATELET COUNT DECREASED3/15 (20%)
    NEUTROPHIL COUNT DECREASED2/15 (13.3%)
    WHITE BLOOD CELL COUNT DECREASED4/15 (26.7%)
    WHITE BLOOD CELL COUNT INCREASED1/15 (6.7%)
    ASPARTATE AMINOTRANSFERASE INCREASED1/15 (6.7%)
    Metabolism and nutrition disorders
    ANOREXIA11/15 (73.3%)
    HYPOCALCAEMIA1/15 (6.7%)
    HYPERGLYCAEMIA1/15 (6.7%)
    HYPOMAGNESAEMIA2/15 (13.3%)
    HYPOALBUMINAEMIA2/15 (13.3%)
    HYPOPHOSPHATAEMIA1/15 (6.7%)
    DECREASED APPETITE2/15 (13.3%)
    Musculoskeletal and connective tissue disorders
    MYALGIA1/15 (6.7%)
    BACK PAIN4/15 (26.7%)
    BONE PAIN1/15 (6.7%)
    NECK PAIN1/15 (6.7%)
    ARTHRALGIA7/15 (46.7%)
    LIMB DISCOMFORT1/15 (6.7%)
    MUSCULAR WEAKNESS1/15 (6.7%)
    PAIN IN EXTREMITY3/15 (20%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR PAIN2/15 (13.3%)
    Nervous system disorders
    TREMOR2/15 (13.3%)
    HEADACHE3/15 (20%)
    AREFLEXIA1/15 (6.7%)
    DIZZINESS1/15 (6.7%)
    DYSGEUSIA6/15 (40%)
    PARAESTHESIA1/15 (6.7%)
    SENSORY DISTURBANCE1/15 (6.7%)
    NEUROPATHY PERIPHERAL4/15 (26.7%)
    RESTLESS LEGS SYNDROME1/15 (6.7%)
    PERIPHERAL SENSORY NEUROPATHY3/15 (20%)
    Psychiatric disorders
    ANXIETY1/15 (6.7%)
    INSOMNIA2/15 (13.3%)
    DEPRESSION1/15 (6.7%)
    RESTLESSNESS1/15 (6.7%)
    Reproductive system and breast disorders
    ADNEXA UTERI PAIN1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    COUGH4/15 (26.7%)
    DYSPNOEA4/15 (26.7%)
    HAEMOPTYSIS1/15 (6.7%)
    NASAL CONGESTION1/15 (6.7%)
    DYSPNOEA EXERTIONAL1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    RASH1/15 (6.7%)
    ALOPECIA9/15 (60%)
    PRURITUS2/15 (13.3%)
    URTICARIA1/15 (6.7%)
    HYPERHIDROSIS1/15 (6.7%)
    SKIN IRRITATION1/15 (6.7%)
    Vascular disorders
    PALLOR1/15 (6.7%)
    FLUSHING1/15 (6.7%)
    HOT FLUSH1/15 (6.7%)
    HYPOTENSION1/15 (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.

    Results Point of Contact

    Name/TitleBristol-Myers Squibb Study Director
    OrganizationBristol-Myers Squibb
    Phone
    EmailClinical.Trials@bms.com
    Responsible Party:
    , ,
    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