Trial Outcomes & Findings for Effect of Rifampin on the Pharmacokinetics of Ixabepilone in Patients With Advanced Cancer (NCT NCT00207090)
NCT ID: NCT00207090
Last Updated: 2020-11-02
Results Overview
Cmax was obtained directly from the concentration-time data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
19 participants
Primary outcome timeframe
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.
Results posted on
2020-11-02
Participant Flow
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)
Participant milestones
| Measure |
All Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
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|---|---|
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Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
All Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
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|---|---|
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Overall Study
Study drug toxicity
|
3
|
|
Overall Study
Chest wall mass larger
|
1
|
|
Overall Study
Disease progression/relapse
|
2
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Effect of Rifampin on the Pharmacokinetics of Ixabepilone in Patients With Advanced Cancer
Baseline characteristics by cohort
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
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|---|---|
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Age, Continuous
|
62 years
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Age, Customized
< 65 years
|
7 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
8 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
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15 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
15 participants
n=5 Participants
|
|
Body surface area (BSA) continuous
|
1.9 square meter
STANDARD_DEVIATION 0.3 • n=5 Participants
|
|
Height continuous
|
173.5 centimeter
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Weight continuous
|
80.3 kilogram
STANDARD_DEVIATION 18.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Of the 15 patients in each group, only those with evaluable pharmacokinetic (PK) results are presented.
Cmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
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Maximum Plasma Concentration (Cmax)
|
338.23 nanogram (ng)/millilter(mL)
Interval 281.78 to 405.99
|
308.37 nanogram (ng)/millilter(mL)
Interval 248.12 to 383.23
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PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
AUC (INF) was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF])
|
3028.70 nanogram (ng)*hour(hr)/mL
Interval 2425.48 to 3781.94
|
1713.07 nanogram (ng)*hour(hr)/mL
Interval 1473.74 to 1991.27
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
T half was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
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Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half)
|
50.85 Hrs
Standard Deviation 18.59
|
36.45 Hrs
Standard Deviation 15.29
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
(MRT \[INF\]) was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
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Mean Residence Time Adjusted for Infusion Time (MRT [INF])
|
50.93 Hrs
Standard Deviation 22.05
|
29.86 Hrs
Standard Deviation 15.31
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
CLT was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
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Total Body Clearance (CLT)
|
28.36 Litres(L)/hr
Standard Deviation 15.04
|
49.99 Litres(L)/hr
Standard Deviation 17.19
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
Vss was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
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|---|---|---|
|
Volume of Distribution at Steady-state (Vss)
|
1323.26 L
Standard Deviation 684.63
|
1447.54 L
Standard Deviation 763.15
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
T max was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Observed Concentration (T Max)
|
1.57 Hrs
Interval 1.5 to 3.3
|
1.50 Hrs
Interval 1.5 to 1.5
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants who were evaluable for PK analysis.
AUC (0-T) was obtained directly from the concentration-time data.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
n=10 Participants
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.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T])
|
3015.45 nanogram (ng)*hr/mL
Standard Deviation 1383.85
|
1478.31 nanogram (ng)*hr/mL
Standard Deviation 486.57
|
PRIMARY outcome
Timeframe: Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration.Population: All treated participants who were evaluable for PK analysis.
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.
Outcome measures
| Measure |
All Participants
n=14 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1
0-8 hours
|
10.04 Ratio
Standard Deviation 5.76
|
—
|
|
Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1
8-24 hours
|
9.29 Ratio
Standard Deviation 5.84
|
—
|
PRIMARY outcome
Timeframe: Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration.Population: All treated participants who were evaluable for PK analysis.
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.
Outcome measures
| Measure |
All Participants
n=10 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22
0-8 hours
|
110.88 Ratio
Standard Deviation 101.91
|
—
|
|
Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22
8-24 hours
|
62.42 Ratio
Standard Deviation 54.35
|
—
|
SECONDARY outcome
Timeframe: From Day 1 to 30 days after the last dose of study drug.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
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
Death
|
0 participants
|
—
|
|
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
Other SAEs
|
4 participants
|
—
|
|
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
Treatment-related AEs
|
15 participants
|
—
|
|
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
Grade 3-4 AEs
|
10 participants
|
—
|
|
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
Discontinuation due to AEs
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Neutrophils (absolute)
|
5 participants
|
—
|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Leukocytes
|
6 participants
|
—
|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Neutrophils + bands (absolute)
|
5 participants
|
—
|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Hemoglobin
|
1 participants
|
—
|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Lymphocytes (absolute)
|
6 participants
|
—
|
|
Number of Participants With Grade 3-4 Hematology Abnormalities
Platelet count
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Screening, Days 1 and 22.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Alanine Aminotransferase
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Aspartate Aminotransferase
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Alkaline Phosphatase
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Bilirubin
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Albumin
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Creatinine
|
0 participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous
Phosphorous (inorganic)
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: Screening, Days 2 and 22.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Calcium (total)
|
0 Participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Magnesium (serum)
|
0 Participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Potassium (serum)
|
0 Participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Sodium (serum)
|
1 Participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Glucose (serum)
|
0 Participants
|
—
|
|
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.
Uric acid
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: From screening to the off treatment visit.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Clinically Meaningful Vital Signs Measures
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: From screening to the off treatment visit.Population: All treated participants.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Abnormal Physical Examination Findings
Weight-related abnormalities
|
3 participants
|
—
|
|
Number of Participants With Abnormal Physical Examination Findings
Other physical examination abnormalities
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion.Population: 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.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
QT Interval Corrected for Heart Rate (QTcF)
0 hour (n=9)
|
3.44 millisecond
Interval -2.06 to 8.95
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
1.5 hour (n=14)
|
5.64 millisecond
Interval 0.54 to 10.74
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
3 hour (n=14)
|
0.57 millisecond
Interval -5.79 to 6.94
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
4 hour (n=11)
|
7.82 millisecond
Interval 3.62 to 12.01
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
6 hour (n=13)
|
6.54 millisecond
Interval 1.73 to 11.35
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
8 hour (n=3)
|
-10.70 millisecond
Interval -31.61 to 10.28
|
—
|
|
QT Interval Corrected for Heart Rate (QTcF)
24 hour (n=10)
|
-1.90 millisecond
Interval -7.18 to 3.38
|
—
|
SECONDARY outcome
Timeframe: Data collected at screening, Day -1 and Day 1 (at 0, 1.5, 3, 4, 6, 8 and 24 hours) after start of infusion.Population: All participants treated with ixabepilone.
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.
Outcome measures
| Measure |
All Participants
n=15 Participants
All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m\^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m\^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles.
|
Ixabepilone + Rifampin
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.
|
|---|---|---|
|
Number of Participants With Identified ECG Abnormalities
Newly identified ECG abnormalities
|
13 Participants
|
—
|
|
Number of Participants With Identified ECG Abnormalities
Discontinuation due to ECG abnormalities
|
1 Participants
|
—
|
|
Number of Participants With Identified ECG Abnormalities
Abnormalities related to QT/QTc interval
|
0 Participants
|
—
|
|
Number of Participants With Identified ECG Abnormalities
Total number of ECG abnormalities
|
13 Participants
|
—
|
Adverse Events
All Participants
Serious events: 4 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Participants
n=15 participants at risk
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.
|
|---|---|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
13.3%
2/15
|
|
Vascular disorders
HYPERTENSION
|
6.7%
1/15
|
|
Immune system disorders
HYPERSENSITIVITY
|
6.7%
1/15
|
|
Gastrointestinal disorders
VOMITING
|
6.7%
1/15
|
|
General disorders
CHEST PAIN
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN
|
6.7%
1/15
|
Other adverse events
| Measure |
All Participants
n=15 participants at risk
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.
|
|---|---|
|
Eye disorders
PHOTOPHOBIA
|
6.7%
1/15
|
|
Eye disorders
LACRIMATION INCREASED
|
6.7%
1/15
|
|
Investigations
HAEMOGLOBIN
|
20.0%
3/15
|
|
Investigations
PLATELET COUNT
|
6.7%
1/15
|
|
Investigations
NEUTROPHIL COUNT
|
13.3%
2/15
|
|
Investigations
WEIGHT DECREASED
|
20.0%
3/15
|
|
Investigations
HAEMOGLOBIN DECREASED
|
20.0%
3/15
|
|
Investigations
WHITE BLOOD CELL COUNT
|
6.7%
1/15
|
|
Investigations
PLATELET COUNT DECREASED
|
20.0%
3/15
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
13.3%
2/15
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
26.7%
4/15
|
|
Investigations
WHITE BLOOD CELL COUNT INCREASED
|
6.7%
1/15
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
6.7%
1/15
|
|
Vascular disorders
PALLOR
|
6.7%
1/15
|
|
Vascular disorders
FLUSHING
|
6.7%
1/15
|
|
Vascular disorders
HOT FLUSH
|
6.7%
1/15
|
|
Vascular disorders
HYPOTENSION
|
6.7%
1/15
|
|
Psychiatric disorders
ANXIETY
|
6.7%
1/15
|
|
Psychiatric disorders
INSOMNIA
|
13.3%
2/15
|
|
Psychiatric disorders
DEPRESSION
|
6.7%
1/15
|
|
Psychiatric disorders
RESTLESSNESS
|
6.7%
1/15
|
|
Hepatobiliary disorders
HEPATOMEGALY
|
6.7%
1/15
|
|
Immune system disorders
HYPERSENSITIVITY
|
6.7%
1/15
|
|
Nervous system disorders
TREMOR
|
13.3%
2/15
|
|
Nervous system disorders
HEADACHE
|
20.0%
3/15
|
|
Nervous system disorders
AREFLEXIA
|
6.7%
1/15
|
|
Nervous system disorders
DIZZINESS
|
6.7%
1/15
|
|
Nervous system disorders
DYSGEUSIA
|
40.0%
6/15
|
|
Nervous system disorders
PARAESTHESIA
|
6.7%
1/15
|
|
Nervous system disorders
SENSORY DISTURBANCE
|
6.7%
1/15
|
|
Nervous system disorders
NEUROPATHY PERIPHERAL
|
26.7%
4/15
|
|
Nervous system disorders
RESTLESS LEGS SYNDROME
|
6.7%
1/15
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
20.0%
3/15
|
|
Gastrointestinal disorders
NAUSEA
|
40.0%
6/15
|
|
Gastrointestinal disorders
RETCHING
|
6.7%
1/15
|
|
Gastrointestinal disorders
VOMITING
|
26.7%
4/15
|
|
Gastrointestinal disorders
DIARRHOEA
|
53.3%
8/15
|
|
Gastrointestinal disorders
DRY MOUTH
|
6.7%
1/15
|
|
Gastrointestinal disorders
DYSPHAGIA
|
6.7%
1/15
|
|
Gastrointestinal disorders
ORAL PAIN
|
6.7%
1/15
|
|
Gastrointestinal disorders
STOMATITIS
|
13.3%
2/15
|
|
Gastrointestinal disorders
CONSTIPATION
|
33.3%
5/15
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
13.3%
2/15
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
6.7%
1/15
|
|
Infections and infestations
RHINITIS
|
6.7%
1/15
|
|
Infections and infestations
ORAL CANDIDIASIS
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
ANOREXIA
|
73.3%
11/15
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
ANAEMIA
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
RASH
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
60.0%
9/15
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
13.3%
2/15
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
SKIN IRRITATION
|
6.7%
1/15
|
|
Reproductive system and breast disorders
ADNEXA UTERI PAIN
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
FALL
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
EXCORIATION
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
26.7%
4/15
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
46.7%
7/15
|
|
Musculoskeletal and connective tissue disorders
LIMB DISCOMFORT
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
20.0%
3/15
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
26.7%
4/15
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
26.7%
4/15
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
6.7%
1/15
|
|
General disorders
PAIN
|
6.7%
1/15
|
|
General disorders
CHILLS
|
40.0%
6/15
|
|
General disorders
FATIGUE
|
86.7%
13/15
|
|
General disorders
FEELING HOT
|
20.0%
3/15
|
|
General disorders
EARLY SATIETY
|
6.7%
1/15
|
|
General disorders
CHEST DISCOMFORT
|
6.7%
1/15
|
|
General disorders
OEDEMA PERIPHERAL
|
26.7%
4/15
|
|
General disorders
INFUSION SITE PAIN
|
13.3%
2/15
|
|
General disorders
INFUSION SITE WARMTH
|
6.7%
1/15
|
|
General disorders
MUCOSAL INFLAMMATION
|
13.3%
2/15
|
|
General disorders
INJECTION SITE REACTION
|
13.3%
2/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN
|
13.3%
2/15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER