Trial Outcomes & Findings for A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer (NCT NCT00422097)
NCT ID: NCT00422097
Last Updated: 2016-03-10
Results Overview
MTD is based on Cycle 1 data only and defined as the maximum dose that can be administered to 6 participants with no more than 1 experiencing a dose-limiting toxicity (DLT) (or fewer than one third of participants if more than 6 receive treatment) with at least 2 participants experiencing a DLT at the next higher dose level. DLT=an event, such as neutropenia; thrombocytopenia; Gr 3 or 4 nausea or diarrhea; Gr 3 fatigue or asthenia; transient arthralgia or recalcitrant myalgia; and prolonged recovery from a toxicity, that occurs during the first course of treatment.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Days 1 through 21 (Cycle 1)
Results posted on
2016-03-10
Participant Flow
Of 58 enrolled, 44 received treatment: 10 no longer met enrollment criteria (2 brain metastases, 2 bowel obstruction, 1 high aspartame aminotransferase \[AST\], 1 high AST/alanine transaminase, 2 low platelets, 1 hospitalized, 1 gastric adverse event \[AE\]); 2 withdrew consent/changed mind; 1 AE; 1 sponsor administrative reason.
Participant milestones
| Measure |
Ixabepilone, 5 mg/d
Ixabepilone, 5 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a dose-limiting toxicity (DLT) in the first 21-day course, a new cohort is opened at the next dose level (10 mg/d). On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 10 mg/d
Ixabepilone, 10 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (15 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 15 mg/d
Ixabepilone, 15 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (20 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 20 mg/d
Ixabepilone, 20 mg, given daily in oral doses on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (25 mg/d). On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 25 mg/d
Ixabepilone, 25 mg/d, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT in the first 21-day course, a new cohort is opened at the next dose level (30 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD. The MTD is the maximum dose that can be given to 6 participants without producing a DLT in more than 1 participant (or fewer than 1/3 if the cohort has more than 6 participants). More participants may be enrolled at any level to provide additional safety data. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 30 mg/d
Ixabepilone, 30 mg, given daily orally on Days 1 through 5 every 21 days. If 2 or more of the first 3 participants experience a DLT within the first 21-day course, this dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD (the maximum dose that can be given to 6 participants without producing a DLT in more than 1 \[or fewer than 1/3 if more than 6 participants in cohort)\]. On all dosing days in Cycle 1, participants to fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, MTD (25 mg), With Famotidine
Cohort opened for Cycle 2, once ixabepilone MTD (25 mg) determined. In Cycle 1, participants received ixabepilone, 25 mg, alone, orally once per day on Days 1 through 21. Then participants crossed over to receive famotidine wirh ixabepilone in Cycle 2. Prior to dosing on Day 1 of Cycle 2, famotidine, 40 mg, administered in an oral dose 2 hours before ixabepilone 25-mg dose.
|
Ixabepilone, MTD (25 mg), With Food
Cohort opened for Cycle 2, after ixabepilone MTD (25 mg) determined. In Cycle 1, participants received ixabepilone, 25 mg, once daily in an oral dose on Days 1 through 5. On all dosing days in Cycle 1, participants fasted at least 4 hours before and 4 hours after dosing. Then participants crossed over to Cycle 2. On Day 1 of Cycle 2, participants allowed a low-fat meal. Participants ingest the specified meal within a 30-minute period and receive ixabepilone, 25 mg, 30 minutes after start of the meal. For the duration of Cycle 2, participants fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|---|---|
|
Dose Level 1
STARTED
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 1
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 2
STARTED
|
0
|
6
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 2
COMPLETED
|
0
|
5
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 2
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 3
STARTED
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 3
COMPLETED
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 4
STARTED
|
0
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
|
Dose Level 4
COMPLETED
|
0
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
|
Dose Level 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 5
STARTED
|
0
|
0
|
0
|
0
|
23
|
0
|
0
|
0
|
|
Dose Level 5
COMPLETED
|
0
|
0
|
0
|
0
|
23
|
0
|
0
|
0
|
|
Dose Level 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dose Level 6
STARTED
|
0
|
0
|
0
|
0
|
0
|
6
|
0
|
0
|
|
Dose Level 6
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
6
|
0
|
0
|
|
Dose Level 6
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Ixabepilone With Famotidine or Food
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
8
|
7
|
|
Ixabepilone With Famotidine or Food
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
8
|
7
|
|
Ixabepilone With Famotidine or Food
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Ixabepilone, 5 mg/d
Ixabepilone, 5 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a dose-limiting toxicity (DLT) in the first 21-day course, a new cohort is opened at the next dose level (10 mg/d). On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 10 mg/d
Ixabepilone, 10 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (15 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 15 mg/d
Ixabepilone, 15 mg, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (20 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 20 mg/d
Ixabepilone, 20 mg, given daily in oral doses on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT during the first 21-day course, a new cohort is opened at the next dose level (25 mg/d). On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 25 mg/d
Ixabepilone, 25 mg/d, given once daily in an oral dose on Days 1 through 5 every 21 days. If none of the first 3 participants experiences a DLT in the first 21-day course, a new cohort is opened at the next dose level (30 mg/d). If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD. The MTD is the maximum dose that can be given to 6 participants without producing a DLT in more than 1 participant (or fewer than 1/3 if the cohort has more than 6 participants). More participants may be enrolled at any level to provide additional safety data. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, 30 mg/d
Ixabepilone, 30 mg, given daily orally on Days 1 through 5 every 21 days. If 2 or more of the first 3 participants experience a DLT within the first 21-day course, this dose level will be considered above the MTD. If 1 of the first 3 participants experiences a DLT, an additional 3 participants will be enrolled at this dose level for a total of 6 participants. If 2 or more of the 6 participants (or 1/3 or more of a cohort with more than 6 participants) experience a DLT, this dose level will be considered above the MTD (the maximum dose that can be given to 6 participants without producing a DLT in more than 1 \[or fewer than 1/3 if more than 6 participants in cohort)\]. On all dosing days in Cycle 1, participants to fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after the dose.
|
Ixabepilone, MTD (25 mg), With Famotidine
Cohort opened for Cycle 2, once ixabepilone MTD (25 mg) determined. In Cycle 1, participants received ixabepilone, 25 mg, alone, orally once per day on Days 1 through 21. Then participants crossed over to receive famotidine wirh ixabepilone in Cycle 2. Prior to dosing on Day 1 of Cycle 2, famotidine, 40 mg, administered in an oral dose 2 hours before ixabepilone 25-mg dose.
|
Ixabepilone, MTD (25 mg), With Food
Cohort opened for Cycle 2, after ixabepilone MTD (25 mg) determined. In Cycle 1, participants received ixabepilone, 25 mg, once daily in an oral dose on Days 1 through 5. On all dosing days in Cycle 1, participants fasted at least 4 hours before and 4 hours after dosing. Then participants crossed over to Cycle 2. On Day 1 of Cycle 2, participants allowed a low-fat meal. Participants ingest the specified meal within a 30-minute period and receive ixabepilone, 25 mg, 30 minutes after start of the meal. For the duration of Cycle 2, participants fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|---|---|
|
Dose Level 2
Still on treatment
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer
Baseline characteristics by cohort
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 5 mg, on Days 1 through 5 every 21 days.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 10 mg, on Days 1 through 5 every 21 days.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 15 mg, on Days 1 through 5 every 21 days.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 20 mg, on Days 1 through 5 every 21 days.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 25 mg, on Days 1 through 5 every 21 days.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants with advanced cancer received daily oral doses of ixabepilone, 30 mg, on Days 1 through 5 every 21 days.
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
32 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
|
Age, Continuous
|
64 years
n=5 Participants
|
62 years
n=7 Participants
|
60 years
n=5 Participants
|
60 years
n=4 Participants
|
56 years
n=21 Participants
|
69 years
n=8 Participants
|
60 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
23 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
21 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
36 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Days 1 through 21 (Cycle 1)Population: All Treated Subjects: All subjects who received at least one dose of ixabepilone were included.
MTD is based on Cycle 1 data only and defined as the maximum dose that can be administered to 6 participants with no more than 1 experiencing a dose-limiting toxicity (DLT) (or fewer than one third of participants if more than 6 receive treatment) with at least 2 participants experiencing a DLT at the next higher dose level. DLT=an event, such as neutropenia; thrombocytopenia; Gr 3 or 4 nausea or diarrhea; Gr 3 fatigue or asthenia; transient arthralgia or recalcitrant myalgia; and prolonged recovery from a toxicity, that occurs during the first course of treatment.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=44 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Ixabepilone
|
25 mg/d
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 1 through 21 (Cycle 1), continuouslyPopulation: All Treated Participants: All participants who received at least one dose of ixabepilone were included.
Adverse events (AEs) graded by CTC version 3. Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=life threatening; Gr 5=Death related to AE. DLT is defined as an event related to ixabepilone that occurs during the first course of treatment. Includes neutropenia; thrombocytopenia; Gr 3 or 4 nausea, vomiting, or diarrhea despite adequate medical intervention and prophylaxis; Gr 3 fatigue or asthenia; transient arthralgia or myalgia unresponsive to medical intervention; any Gr 3 nonhematologic toxicity; and prolonged recovery from a toxicity.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Clostridium difficile colitis (Grade 3)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Ileus (Grade 3)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Abdominal pain (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Fatigue (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Neutropenic fever (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Neutropenic fever (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Dehydration (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Diarrhea (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Hypokalemia (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Nausea (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Vomiting (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Mucosal inflammation (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Neutropenia (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Hypokalemia (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Hypophosphatemia (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Thrombocytopenia (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade
Sudden death (Grade 5)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Days 1 through 21 (Cycle 1), continuouslyPopulation: All Treated Subjects: All subjects who received at least 1 dose of ixabepilone.
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
AEs leading to discontinuation
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
Death
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
Treatment-related AEs
|
2 Participants
|
6 Participants
|
3 Participants
|
1 Participants
|
12 Participants
|
5 Participants
|
|
Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
AEs
|
3 Participants
|
6 Participants
|
3 Participants
|
2 Participants
|
20 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline and Days 1, 8, and 15 of Cycle 1 (21 days)Population: All Treated Subjects: All subjects who received at least one dose of ixabepilone were included.
Lower limit of normal (LLN)=lowest level of normal among all laboratory ranges. Hemoglobin (g/dL): Gr 1: 10.0-\<LLN; Gr 2: 8.0-\<10.0; Gr 3:6.5-\<8.0; Gr 4: 6.5. Leukocytes (c/uL): Gr 1: 3.0-\<LLN; Gr 2: 2.0-\<3.0; Gr 3: 1.0-\<2.0; Gr 4: \<1.0. Lymphocytes (c/uL): Gr 1: 0.8-\<1.5; Gr 2: 0.5-\<0.8; Gr 3: 0.2-\<0.5; Gr 4: \<0.2. Neutrophils (Absolute)(c/uL): Gr 1: 1.5-\<2.0; Gr 2: 1.0-\<1.5; Gr 3: 0.5-\<1.0; Gr 4: \<0.5. Neutrophils + Bands (c/uL): Gr 1: 1.5-\<2.0; Gr 2: 1.0-\<1.5; Gr 3: 0.5-\<1.0; Gr 4: \<0.5. Platelet Count (c/uL):Gr 1: 75.0-\<LLN; Gr 2: 50.0-\<75.0; Gr 3: 25.0-\<50.0; Gr 4: \<25.0.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=44 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Hemoglobin (Grade 1)
|
19 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Hemoglobin (Grade 2)
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Hemoglobin (Grade 3)
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Hemoglobin (Grade 4)
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Leukocytes (Grade 1)
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Leukocytes (Grade 2)
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Leukocytes (Grade 3)
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Leukocytes (Grade 4)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Lymphocytes (Absolute) (Grade 1)
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Lymphocytes (Absolute) (Grade 2)
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Lymphocytes (Absolute) (Grade 3)
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Lymphocytes (Absolute) (Grade 4)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils (Absolute) (Grade 1)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils (Absolute) (Grade 2)
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils (Absolute) (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils (Absolute) (Grade 4)
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils + Bands (Absolute) (Grade 1)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils + Bands (Absolute) (Grade 2)
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils + Bands (Absolute) (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Neutrophils + Bands (Absolute) (Grade 4)
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Platelet Count (Grade 1)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Platelet Count (Grade 2)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Platelet Count (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Laboratory Values by Worst CTC Grade
Platelet Count (Grade 4)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 5 of Cycle 1Population: All participants who received ixabepilone and who had adequate concentration profiles
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Ixabepilone
Day1 (n=3, n=6, n=3, n=3, n=23, n=6)
|
4.02 ng/mL
Standard Deviation 1.99
|
25.93 ng/mL
Standard Deviation 20.47
|
16.04 ng/mL
Standard Deviation 16.76
|
24.10 ng/mL
Standard Deviation 19.96
|
36.14 ng/mL
Standard Deviation 25.18
|
43.67 ng/mL
Standard Deviation 20.87
|
|
Maximum Plasma Concentration (Cmax) of Ixabepilone
Day 5 (n=2, n=6, n=3, n=3, n=22, n=6)
|
2.45 ng/mL
Standard Deviation 0.42
|
20.34 ng/mL
Standard Deviation 23.07
|
22.17 ng/mL
Standard Deviation 12.40
|
32.73 ng/mL
Standard Deviation 24.97
|
57.99 ng/mL
Standard Deviation 99.77
|
66.48 ng/mL
Standard Deviation 62.64
|
SECONDARY outcome
Timeframe: Days 1 and 5 of Cycle 1Population: All participants who received ixabepilone and who had adequate concentration profiles
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Ixabepilone
Day1 (n=3, n=6, n=3, n=3, n=23, n=6)
|
2.0 Hour
Interval 1.0 to 2.0
|
1.8 Hour
Interval 1.0 to 3.0
|
4.0 Hour
Interval 2.0 to 4.0
|
2.0 Hour
Interval 2.0 to 3.0
|
2.0 Hour
Interval 0.5 to 24.0
|
3.0 Hour
Interval 1.5 to 4.0
|
|
Time of Maximum Plasma Concentration (Tmax) of Ixabepilone
Day 5 (n=2, n=6, n=3, n=3, n=22, n=6)
|
2.3 Hour
Interval 1.5 to 3.0
|
2.5 Hour
Interval 1.0 to 5.0
|
5.0 Hour
Interval 1.5 to 6.0
|
1.5 Hour
Interval 1.5 to 2.0
|
1.8 Hour
Interval 0.5 to 6.0
|
3.5 Hour
Interval 2.0 to 8.0
|
SECONDARY outcome
Timeframe: Days 1 and 5 of Cycle 1Population: All participants who received ixabepilone and who had adequate concentration profiles.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC[TAU])of Ixabepilone
Day 1 (n=3, n=6, n=3, n=3, n=23, n=6)
|
28.40 ng*h/mL
Standard Deviation 29.73
|
91.79 ng*h/mL
Standard Deviation 62.45
|
120.58 ng*h/mL
Standard Deviation 152.23
|
120.82 ng*h/mL
Standard Deviation 73.62
|
195.96 ng*h/mL
Standard Deviation 177.39
|
252.01 ng*h/mL
Standard Deviation 153.26
|
|
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC[TAU])of Ixabepilone
Day 5 (n=2, n=6, n=3, n=3, n=22, n=6)
|
21.83 ng*h/mL
Standard Deviation 28.59
|
143.85 ng*h/mL
Standard Deviation 134.15
|
179.82 ng*h/mL
Standard Deviation 126.95
|
222.73 ng*h/mL
Standard Deviation 136.49
|
348.07 ng*h/mL
Standard Deviation 370.95
|
545.42 ng*h/mL
Standard Deviation 441.93
|
SECONDARY outcome
Timeframe: Day 5 of Cycle 1Population: All participants who received ixabepilone and who had adequate concentration profiles
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=2 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=22 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Plasma Half-life (T-Half) of Ixabepilone
|
18.56 Hours
Standard Deviation NA
Only 2 participants in this Arm on Day 5, so SD is not appropriate.
|
47.00 Hours
Standard Deviation 82.68
|
24.32 Hours
Standard Deviation 17.68
|
35.25 Hours
Standard Deviation 20.63
|
35.62 Hours
Standard Deviation 17.48
|
34.14 Hours
Standard Deviation 14.16
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: All participants who received ixabepilone and who had adequate concentration profiles. Participants received MTD (25 mg) ixabepilone without famotidine (Cycle 1) and then were crossed over to a cycle in which they received MTD (25 mg) ixabepilone with famotidine (Cycle 2).
After the MTD has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=8 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fasted (Cycle 1)
|
38.11 ng/mL
Standard Deviation 29.48
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fed (Cycle 2)
|
44.76 ng/mL
Standard Deviation 38.69
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: All participants who received ixabepilone and who had adequate concentration profiles. Participants received MTD (25 mg).
After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=8 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax)of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fasted (Cycle 1)
|
2.0 ng/mL
Interval 0.5 to 5.0
|
—
|
—
|
—
|
—
|
—
|
|
Time of Maximum Plasma Concentration (Tmax)of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fed (Cycle 2)
|
4.0 ng/mL
Interval 2.0 to 6.0
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: All participants who received ixabepilone and who had adequate concentration profiles. Participants received MTD (25 mg).
After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=8 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fasted (Cycle 1)
|
190.22 ng*h/mL
Standard Deviation 128.14
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts
Fed (Cycle 2)
|
243.46 ng*h/mL
Standard Deviation 99.91
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: Participants who received ixabepilone, at the MTD of 25 mg, alone in Cycle 1 and had adequate concentration profiles. Participants then were crossed over to a cycle in which they received MTD (25 mg) ixabepilone with famotidine,40 mg, on Day 1 of Cycle 2.
After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=7 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
Without Famotidine (Cycle 1)
|
36.91 ng/mL
Standard Deviation 29.79
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
With Famotidine (Cycle 2)
|
66.16 ng/mL
Standard Deviation 63.91
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: Participants who received ixabepilone, at the MTD of 25 mg, alone in Cycle 1 and had adequate concentration profiles. Participants then were crossed over to a cycle in which they received MTD (25 mg) ixabepilone with famotidine,40 mg, on Day 1 of Cycle 2.
After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=7 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
Without Famotidine (Cycle 1)
|
3.0 ng/mL
Interval 1.0 to 24.0
|
—
|
—
|
—
|
—
|
—
|
|
Time of Maximum Plasma Concentration (Tmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
With Famotidine (Cycle 2)
|
4.0 ng/mL
Interval 2.0 to 6.0
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)Population: Participants who received ixabepilone, at the MTD of 25 mg, alone in Cycle 1 and had adequate concentration profiles. Participants then were crossed over to a cycle in which they received MTD (25 mg) ixabepilone with famotidine,40 mg, on Day 1 of Cycle 2.
After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given alone once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=7 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
Without Famotidine (Cycle 1)
|
218.36 ng*h/mL
Standard Deviation 260.55
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts
With Famotidine (Cycle 2)
|
276.30 ng*h/mL
Standard Deviation 179.20
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At screening and predose Day 1, Cycle 1 (21 days)Population: Although physical examinations and ECGs were performed, the findings were not summarized.
Physical examination evaluated height, weight, Eastern Cooperative Oncology Group performance status, adverse events, and abnormal laboratory findings and included a neurologic examination to evaluate deep tendon reflexes, sensory modalities, and motor strength. Participants also underwent a 12-lead ECG screening. Physical examination findings and ECG findings were considered clinically significant at the investigator's discretion.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
n=3 Participants
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
n=23 Participants
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
n=6 Participants
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Significant Findings on Physical Examination or Electrocardiogram (ECG)
With abnormal physical examination findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Significant Findings on Physical Examination or Electrocardiogram (ECG)
With abnormal ECG results
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At screening and predose Day 1, Cycle 1 (21 days)Population: All Treated Subjects: All subjects who received at least one dose of ixabepilone were included.
Upper limit of normal (ULN)=upper level of normal among all laboratory ranges. Alkaline phosphatase(U/L): Gr 3: \>5.0-20.0\*ULN; Gr 4: \>20.0\*ULN. Sodium (mEq/L): Gr 3: 120-\<130 or \>155-160; Gr 4 \<120. Potassium (mEq/L): Gr 3: 2.5-\<3.0 or \>6.0-7.0; Gr 4: \<2.5 or \>7.0. Calcium (mg/dL): Gr 3: 6.0-\<7.0 or \>12.5-13.5; Gr 4: \<6.0 or \>13.5. Inorganic phosphorus (mg/dL): Gr 3: 1.0-\<2.0; Gr 4: \<1.0. Albumin (g/dL): Gr 3: \<2.0.
Outcome measures
| Measure |
Ixabepilone, 5 mg/d
n=44 Participants
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 10 mg/d
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 15 mg/d
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 20 mg/d
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 25 mg/d
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
Ixabepilone, 30 mg/d
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment. For Cycles 2 and greater, participants must fast 1 hour before and 2 hours after ixabepilone dose.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low sodium (Grade 3)
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
High sodium (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low albumin (Grade 3)
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low alkaline phosphatase (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low potassium (Grade 3)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low potassium (Grade 4)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low total calcium (Grade 4)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels
Low inorganic phosphorus (Grade 4)
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Ixabepilone, 5 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Ixabepilone, 10 mg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Ixabepilone, 15 mg
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Ixabepilone, 20 mg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Ixabepilone, 25 mg
Serious events: 6 serious events
Other events: 20 other events
Deaths: 0 deaths
Ixabepilone, 30 mg
Serious events: 5 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ixabepilone, 5 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days
|
Ixabepilone, 10 mg
n=6 participants at risk
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days
|
Ixabepilone, 15 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days
|
Ixabepilone, 20 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days
|
Ixabepilone, 25 mg
n=23 participants at risk
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days
|
Ixabepilone, 30 mg
n=6 participants at risk
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
33.3%
2/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
33.3%
2/6
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Infections and infestations
Infection
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3
|
33.3%
2/6
|
66.7%
2/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Infections and infestations
Catheter-related infection
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
50.0%
3/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Asthenia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Chest pain
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Sudden death
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
General disorders
Noncardiac chest pain
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor hemorrhage
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nonsmall cell lung cancer
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
Other adverse events
| Measure |
Ixabepilone, 5 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 5 mg, on Days 1-5 every 21 days
|
Ixabepilone, 10 mg
n=6 participants at risk
Participants received daily oral doses of ixabepilone, 10 mg, on Days 1-5 every 21 days
|
Ixabepilone, 15 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 15 mg, on Days 1-5 every 21 days
|
Ixabepilone, 20 mg
n=3 participants at risk
Participants received daily oral doses of ixabepilone, 20 mg, on Days 1-5 every 21 days
|
Ixabepilone, 25 mg
n=23 participants at risk
Participants received daily oral doses of ixabepilone, 25 mg, on Days 1-5 every 21 days
|
Ixabepilone, 30 mg
n=6 participants at risk
Participants received daily oral doses of ixabepilone, 30 mg, on Days 1-5 every 21 days
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Psychiatric disorders
Depression
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Nervous system disorders
Aphonia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Investigations
Weight decreased
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Investigations
Culture urine positive
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Investigations
Blood potassium decreased
|
33.3%
1/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
8.7%
2/23
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
33.3%
1/3
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
33.3%
2/6
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
8.7%
2/23
|
16.7%
1/6
|
|
Nervous system disorders
Convulsion
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3
|
16.7%
1/6
|
66.7%
2/3
|
33.3%
1/3
|
30.4%
7/23
|
66.7%
4/6
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3
|
16.7%
1/6
|
100.0%
3/3
|
33.3%
1/3
|
26.1%
6/23
|
50.0%
3/6
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3
|
33.3%
2/6
|
33.3%
1/3
|
33.3%
1/3
|
17.4%
4/23
|
33.3%
2/6
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
8.7%
2/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
1/3
|
33.3%
1/3
|
17.4%
4/23
|
33.3%
2/6
|
|
Gastrointestinal disorders
Abdominal mass
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
33.3%
2/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
13.0%
3/23
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Gastrointestinal disorders
Gastroesophogeal reflux disease
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
8.7%
2/23
|
0.00%
0/6
|
|
Infections and infestations
Candidiasis
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Infections and infestations
Oncyhomyocosis
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Renal and urinary disorders
Urethral stenosis
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
1/3
|
0.00%
0/6
|
66.7%
2/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
8.7%
2/23
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
1/3
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/3
|
34.8%
8/23
|
33.3%
2/6
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3
|
33.3%
2/6
|
33.3%
1/3
|
0.00%
0/3
|
21.7%
5/23
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
13.0%
3/23
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
33.3%
2/6
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
17.4%
4/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
33.3%
1/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
13.0%
3/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
66.7%
2/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
66.7%
2/3
|
50.0%
3/6
|
0.00%
0/3
|
0.00%
0/3
|
21.7%
5/23
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
17.4%
4/23
|
33.3%
2/6
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
0.00%
0/3
|
50.0%
3/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Pain
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/3
|
13.0%
3/23
|
16.7%
1/6
|
|
General disorders
Chills
|
33.3%
1/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
13.0%
3/23
|
33.3%
2/6
|
|
General disorders
Edema
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
General disorders
Fatigue
|
66.7%
2/3
|
66.7%
4/6
|
33.3%
1/3
|
33.3%
1/3
|
56.5%
13/23
|
50.0%
3/6
|
|
General disorders
Pyrexia
|
0.00%
0/3
|
66.7%
4/6
|
33.3%
1/3
|
0.00%
0/3
|
13.0%
3/23
|
0.00%
0/6
|
|
General disorders
Chest pain
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Gait disturbance
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Implant site pain
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
General disorders
Edema peripheral
|
33.3%
1/3
|
33.3%
2/6
|
0.00%
0/3
|
0.00%
0/3
|
4.3%
1/23
|
0.00%
0/6
|
|
General disorders
Mucosal inflammation
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
33.3%
2/6
|
|
General disorders
Noncardiac chest pain
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/23
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrohordon
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/23
|
0.00%
0/6
|
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 \<or=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