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Study of MLN8237 in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT00962091
Recruitment Status : Completed
First Posted : August 19, 2009
Results First Posted : March 12, 2019
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced Solid Tumors
Intervention Drug: Alisertib
Enrollment 53
Recruitment Details Participants took part in the study at 3 investigative sites in the United States from 25 September 2009 to 01 July 2014.
Pre-assignment Details Participants with a diagnosis of advanced solid tumors were enrolled to receive alisertib in 1 of 4 parts: Dose Escalation, Part A (relative bioavailability), Part B (food effect and multiple-dose pharmacokinetics of alisertib oral solution [OS]), and Part C (food effect and safety of alisertib enteric-coated tablets [ECT]).
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability OS/PIC (Sequence A) Part A: Relative Bioavailability PIC/OS (Sequence B) Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B) Part C: ECT Food Effect Fed/Fasted (Sequence A) Part C: ECT Food Effect Fasted/Fed (Sequence B)
Hide Arm/Group Description A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Period Title: Overall Study
Started 4 9 10 3 3 12 12
Completed 3 7 9 2 3 11 11
Not Completed 1 2 1 1 0 1 1
Reason Not Completed
Withdrawal by Subject             1             2             1             1             0             1             0
Adverse Event             0             0             0             0             0             0             1
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability OS/PIC (Sequence A) Part A: Relative Bioavailability PIC/OS (Sequence B) Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B) Part C: ECT Food Effect Fed/Fasted (Sequence A) Part C: ECT Food Effect Fasted/Fed (Sequence B) Total
Hide Arm/Group Description A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Total of all reporting groups
Overall Number of Baseline Participants 4 9 10 3 3 12 12 53
Hide Baseline Analysis Population Description
Safety population is defined as all participants who receive any amount of alisertib. Efficacy analysis included all participants who had a baseline response assessment and at least one on-study response assessment.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
58.3
(57 to 59)
54.6
(20 to 71)
54.0
(36 to 70)
51.7
(31 to 64)
57.7
(53 to 61)
57.4
(39 to 72)
55.2
(46 to 69)
55.5
(20 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
Female
3
  75.0%
2
  22.2%
5
  50.0%
1
  33.3%
1
  33.3%
7
  58.3%
9
  75.0%
28
  52.8%
Male
1
  25.0%
7
  77.8%
5
  50.0%
2
  66.7%
2
  66.7%
5
  41.7%
3
  25.0%
25
  47.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
0 0 2 0 1 2 1 6
Not Hispanic or Latino Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
4 9 8 3 2 10 11 47
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
4 8 9 3 2 12 11 49
Black or African American Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
0 0 1 0 1 0 1 3
Asian Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
0 1 0 0 0 0 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
4 9 10 3 3 12 12 53
Height   [1] 
Mean (Full Range)
Unit of measure:  Cm
Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 11 participants 10 participants 50 participants
167.7
(163 to 175)
172.6
(154 to 185)
172.8
(160 to 188)
160.3
(157 to 163)
169.1
(159 to 182)
169.2
(159 to 179)
160.5
(152 to 169)
167.4
(152 to 188)
[1]
Measure Analysis Population Description: Number analyzed is the number of participants with available Baseline Height data.
Weight  
Mean (Full Range)
Unit of measure:  Kg
Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 12 participants 12 participants 53 participants
72.7
(66 to 80)
85.5
(68 to 118)
81.4
(65 to 120)
66.3
(45 to 99)
77.7
(59 to 99)
73.0
(45 to 98)
66.1
(43 to 101)
74.7
(43 to 120)
Body Surface Area (BSA)   [1] [2] 
Mean (Full Range)
Unit of measure:  M^2
Number Analyzed 4 participants 9 participants 10 participants 3 participants 3 participants 11 participants 10 participants 50 participants
1.84
(1.7 to 2.0)
2.02
(1.8 to 2.4)
1.97
(1.7 to 2.5)
1.69
(1.4 to 2.1)
1.90
(1.6 to 2.2)
1.82
(1.4 to 2.2)
1.68
(1.4 to 2.1)
1.85
(1.4 to 2.5)
[1]
Measure Description: BSA = sqrt [height (cm) x weight (kg)/3600]
[2]
Measure Analysis Population Description: Number analyzed is the number of participants with available Baseline BSA data.
1.Primary Outcome
Title Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Time Frame Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual adverse event (AE) that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.
Arm/Group Title Part A: Alisertib OS Part A: Alisertib PIC
Hide Arm/Group Description:
Alisertib 25 mg, OS, once on Day 1 in Cycle 1 or Cycle 2.
Alisertib 50 mg, PIC, orally once on Day 1 in Cycle 1 or Cycle 2.
Overall Number of Participants Analyzed 17 18
Mean (Standard Deviation)
Unit of Measure: nM/mg
58.78  (22.583) 31.40  (11.404)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A: Alisertib OS, Part A: Alisertib PIC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.90
Confidence Interval (2-Sided) 90%
1.52 to 2.37
Estimation Comments The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 Cmax values (difference=OS–PIC). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.
2.Primary Outcome
Title Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Hide Description Dose normalized AUClast was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Time Frame Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.
Arm/Group Title Part A: Alisertib OS Part A: Alisertib PIC
Hide Arm/Group Description:
Alisertib 25 mg, OS, once on Day 1 in Cycle 1 or Cycle 2.
Alisertib 50 mg, PIC, orally once on Day 1 in Cycle 1 or Cycle 2.
Overall Number of Participants Analyzed 17 17
Mean (Standard Deviation)
Unit of Measure: nM*hr/mg
530.18  (177.750) 372.53  (145.190)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A: Alisertib OS, Part A: Alisertib PIC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.38
Confidence Interval (2-Sided) 90%
1.08 to 1.78
Estimation Comments The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUClast values (difference=OS–PIC). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.
3.Primary Outcome
Title Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Hide Description Not performed.
Time Frame Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Arm/Group Title Part B: Alisertib OS (Fed State) Part B: Alisertib OS (Fasted State)
Hide Arm/Group Description:
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): Alisertib 35 mg oral solution (OS), in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle.
Alisertib 35 mg, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Primary Outcome
Title Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Hide Description Not performed.
Time Frame Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Arm/Group Title Part B: Alisertib OS (Fed State) Part B: Alisertib OS (Fasted State)
Hide Arm/Group Description:
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): Alisertib 35 mg oral solution (OS), in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle.
Alisertib 35 mg, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Primary Outcome
Title Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration
Hide Description Not performed.
Time Frame Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Arm/Group Title Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B)
Hide Arm/Group Description:
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Hide Description Not performed.
Time Frame Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Arm/Group Title Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B)
Hide Arm/Group Description:
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Primary Outcome
Title Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Hide Description Not performed.
Time Frame Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
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Hide Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Arm/Group Title Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B)
Hide Arm/Group Description:
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Primary Outcome
Title Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Hide Description Participants were randomized to receive 50-mg alisertib as an ECT (single, 50-mg strength tablets) under fasted or fed (following a standardized high-fat meal) conditions.
Time Frame Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
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Hide Analysis Population Description
PK-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
Arm/Group Title Part C: Alisertib ECT (Fasted State) Part C: Alisertib ECT (Fed State)
Hide Arm/Group Description:
Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.
Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: nM
1757.9  (924.5) 1401.2  (501.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C: Alisertib ECT (Fasted State), Part C: Alisertib ECT (Fed State)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 90%
0.66 to 1.06
Estimation Comments The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 Cmax values (difference=Fed–Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.
9.Primary Outcome
Title Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
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Hide Analysis Population Description
The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
Arm/Group Title Part C: Alisertib ECT (Fasted State) Part C: Alisertib ECT (Fed State)
Hide Arm/Group Description:
Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.
Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: nM*h
23928.6  (14343.56) 24135.0  (11757.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C: Alisertib ECT (Fasted State), Part C: Alisertib ECT (Fed State)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 90%
0.80 to 1.34
Estimation Comments The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUClast values (difference=Fed–Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.
10.Primary Outcome
Title Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
Arm/Group Title Part C: Alisertib ECT (Fasted State) Part C: Alisertib ECT (Fed State)
Hide Arm/Group Description:
Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.
Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Overall Number of Participants Analyzed 11 14
Mean (Standard Error)
Unit of Measure: nM*h
30627.3  (21000.29) 28507.1  (15637.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C: Alisertib ECT (Fasted State), Part C: Alisertib ECT (Fed State)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.94
Confidence Interval (2-Sided) 90%
0.68 to 1.32
Estimation Comments The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUC values (difference=Fed–Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.
11.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame Up to 30 days after the last dose of study drug (up to 27.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Hide Arm/Group Description:
A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 4 19 6 24
Measure Type: Number
Unit of Measure: participants
AE 4 19 6 24
SAE 2 4 2 11
12.Primary Outcome
Title Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5%
Hide Description Laboratory AEs reported at an incidence of at least 5% overall in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, metabolism and nutrition disorders, investigations, and hepatobiliary disorders. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment­-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame Up to 30 days after the last dose of study drug (up to 27.4 months)
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Hide Analysis Population Description
Safety Population is defined as all participants who receive any amount of alisertib.
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Hide Arm/Group Description:
A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 4 19 6 24
Measure Type: Number
Unit of Measure: participants
Neutropenia 3 8 2 21
Leukopenia 3 7 2 17
Anaemia 3 4 2 15
Thrombocytopenia 4 3 3 10
Lymphopenia 0 3 0 3
Hypomagnesaemia 0 0 1 7
Hyperglycaemia 0 1 1 3
Hypokalaemia 0 0 1 3
White blood cell count decreased 0 0 1 5
Aspartate aminotransferase increased 1 0 0 6
Gamma-glutamyltransferase increased 0 1 0 2
Lymphocyte count decreased 0 0 0 3
Neutrophil count decreased 0 1 0 2
Hyperbilirubinaemia 1 0 0 3
13.Primary Outcome
Title Number of Participants With Abnormal Vital Signs Reported as Adverse Events
Hide Description Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study.
Time Frame Up to 30 days after the last dose of study drug (up to 24 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who receive any amount of alisertib.
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Hide Arm/Group Description:
A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 4 19 6 24
Measure Type: Number
Unit of Measure: participants
Hypertension 1 0 1 1
Hypotension 0 1 1 0
Tachycardia 1 1 1 0
Sinus bradycardia 0 0 0 1
14.Secondary Outcome
Title Best Overall Response (CR+PR) Based on Investigator’s Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description Best overall response is defined as the number of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum LD since the treatment started.
Time Frame At the completion of Cycle 2 and every 2 cycles (every 6 weeks) until Cycle 6 (18 weeks). After Cycle 6 (18 weeks), CT/MRI scans (with contrast) were to be performed every 3 cycles (9 weeks) until PD was documented.
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Hide Analysis Population Description
Efficacy analysis included all participants who had a baseline response assessment and at least one on-study response assessment.
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability OS/PIC (Sequence A) Part A: Relative Bioavailability PIC/OS (Sequence B) Part B: OS Food Effect Fed/Fasted (Sequence A) Part B: OS Food Effect Fasted/Fed (Sequence B) Part C: ECT Food Effect Fed/Fasted (Sequence A) Part C: ECT Food Effect Fasted/Fed (Sequence B)
Hide Arm/Group Description:
A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Overall Number of Participants Analyzed 2 8 9 3 3 12 12
Measure Type: Number
Unit of Measure: participants
Best Overall Response of CR or PR 0 0 0 0 0 0 0
Best Overall Response of Stable Disease 0 1 5 2 1 6 6
Time Frame Up to 30 days after the last dose of study drug (up to 27.4 months approximately)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Hide Arm/Group Description A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
All-Cause Mortality
Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
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Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/4 (50.00%)   4/19 (21.05%)   2/6 (33.33%)   11/24 (45.83%) 
Blood and lymphatic system disorders         
Anaemia  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Neutropenia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Febrile neutropenia  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  2/24 (8.33%) 
Gastrointestinal disorders         
Vomiting  2  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Nausea  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Small intestinal obstruction  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
General disorders         
Fatigue  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Pain  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Pyrexia  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Hepatobiliary disorders         
Hyperbilirubinaemia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Bile duct stone  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Infections and infestations         
Sepsis  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Urinary tract infection  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Gastroenteritis viral  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Metabolism and nutrition disorders         
Dehydration  1  1/4 (25.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Musculoskeletal pain  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Renal and urinary disorders         
Anuria  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Hydronephrosis  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Renal failure acute  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Reproductive system and breast disorders         
Female genital tract fistula  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Respiratory, thoracic and mediastinal disorders         
Respiratory arrest  1 [1]  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
2
Term from vocabulary, MedDRA
[1]
One treatment-emergent death occurred during treatment with alisertib and is not related.
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Frequency Threshold for Reporting Other Adverse Events 5%
Dose Escalation Cohort Part A: Relative Bioavailability Part B: OS Food Effect Part C: ECT Food Effect
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   19/19 (100.00%)   6/6 (100.00%)   24/24 (100.00%) 
Blood and lymphatic system disorders         
Neutropenia  1  2/4 (50.00%)  8/19 (42.11%)  2/6 (33.33%)  17/24 (70.83%) 
Leukopenia  1  3/4 (75.00%)  7/19 (36.84%)  2/6 (33.33%)  13/24 (54.17%) 
Anaemia  1  3/4 (75.00%)  4/19 (21.05%)  2/6 (33.33%)  13/24 (54.17%) 
Thrombocytopenia  1  4/4 (100.00%)  3/19 (15.79%)  3/6 (50.00%)  7/24 (29.17%) 
Lymphopenia  1  0/4 (0.00%)  3/19 (15.79%)  0/6 (0.00%)  3/24 (12.50%) 
Leukocytosis  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Cardiac disorders         
Tachycardia  1  1/4 (25.00%)  1/19 (5.26%)  1/6 (16.67%)  1/24 (4.17%) 
Endocrine disorders         
Inappropriate antidiuretic hormone secretion  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Eye disorders         
Vision blurred  1  1/4 (25.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Diplopia  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Eyelid pain  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Lacrimation increased  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Visual impairment  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  0/4 (0.00%)  11/19 (57.89%)  1/6 (16.67%)  13/24 (54.17%) 
Nausea  1  2/4 (50.00%)  10/19 (52.63%)  2/6 (33.33%)  9/24 (37.50%) 
Stomatitis  1  4/4 (100.00%)  7/19 (36.84%)  5/6 (83.33%)  6/24 (25.00%) 
Vomiting  1  0/4 (0.00%)  7/19 (36.84%)  1/6 (16.67%)  5/24 (20.83%) 
Constipation  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  6/24 (25.00%) 
Abdominal pain  1  1/4 (25.00%)  1/19 (5.26%)  1/6 (16.67%)  3/24 (12.50%) 
Abdominal distension  1  1/4 (25.00%)  1/19 (5.26%)  0/6 (0.00%)  3/24 (12.50%) 
Dysphagia  1  0/4 (0.00%)  2/19 (10.53%)  1/6 (16.67%)  1/24 (4.17%) 
Abdominal pain upper  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  2/24 (8.33%) 
Flatulence  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  1/24 (4.17%) 
Abdominal discomfort  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  0/24 (0.00%) 
Dry mouth  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Dyspepsia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Ascites  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Colitis  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Haematochezia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Haemorrhoids  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Ileus  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
General disorders         
Fatigue  1  3/4 (75.00%)  12/19 (63.16%)  4/6 (66.67%)  11/24 (45.83%) 
Asthenia  1  1/4 (25.00%)  2/19 (10.53%)  1/6 (16.67%)  3/24 (12.50%) 
Pyrexia  1  2/4 (50.00%)  2/19 (10.53%)  2/6 (33.33%)  1/24 (4.17%) 
Oedema peripheral  1  1/4 (25.00%)  2/19 (10.53%)  0/6 (0.00%)  1/24 (4.17%) 
Early satiety  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  1/24 (4.17%) 
Chest discomfort  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Mucosal inflammation  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Hepatobiliary disorders         
Hyperbilirubinaemia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  3/24 (12.50%) 
Jaundice  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Immune system disorders         
Drug hypersensitivity  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Infections and infestations         
Oral candidiasis  1  1/4 (25.00%)  2/19 (10.53%)  2/6 (33.33%)  4/24 (16.67%) 
Sinusitis  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  2/24 (8.33%) 
Upper respiratory tract infection  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  1/24 (4.17%) 
Urinary tract infection  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  2/24 (8.33%) 
Nasopharyngitis  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Oral herpes  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Clostridium difficile infection  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Fungal skin infection  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Herpes simplex  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Skin infection  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Vaginal infection  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications         
Fall  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  1/24 (4.17%) 
Contusion  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Forearm fracture  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Investigations         
Weight decreased  1  0/4 (0.00%)  3/19 (15.79%)  0/6 (0.00%)  5/24 (20.83%) 
White blood cell count decreased  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  5/24 (20.83%) 
Aspartate aminotransferase increased  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  4/24 (16.67%) 
Gamma-glutamyltransferase increased  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  2/24 (8.33%) 
Neutrophil count decreased  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  2/24 (8.33%) 
Alanine aminotransferase increased  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Blood urea increased  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Lymphocyte count decreased  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Blood phosphorus decreased  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  2/4 (50.00%)  7/19 (36.84%)  1/6 (16.67%)  7/24 (29.17%) 
Dehydration  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  4/24 (16.67%) 
Hypomagnesaemia  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  5/24 (20.83%) 
Hyperglycaemia  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  2/24 (8.33%) 
Hypokalaemia  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  3/24 (12.50%) 
Hypoalbuminaemia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  1/24 (4.17%) 
Gout  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Hypercalcaemia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Hyperuricaemia  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Hypophosphataemia  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Hyponatraemia  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/4 (25.00%)  6/19 (31.58%)  0/6 (0.00%)  4/24 (16.67%) 
Myalgia  1  0/4 (0.00%)  4/19 (21.05%)  0/6 (0.00%)  0/24 (0.00%) 
Pain in extremity  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  2/24 (8.33%) 
Arthralgia  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Muscular weakness  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Musculoskeletal discomfort  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Musculoskeletal pain  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  0/24 (0.00%) 
Axillary mass  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Flank pain  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Muscle spasms  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Musculoskeletal chest pain  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Pathological fracture  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cancer pain  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Tumour flare  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Nervous system disorders         
Headache  1  2/4 (50.00%)  2/19 (10.53%)  0/6 (0.00%)  4/24 (16.67%) 
Somnolence  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  2/24 (8.33%) 
Dizziness  1  1/4 (25.00%)  2/19 (10.53%)  0/6 (0.00%)  0/24 (0.00%) 
Dysgeusia  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  1/24 (4.17%) 
Cognitive disorder  1  2/4 (50.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Memory impairment  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  0/24 (0.00%) 
Balance disorder  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Brain oedema  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Hypoaesthesia  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Nerve compression  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Psychiatric disorders         
Depression  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  2/24 (8.33%) 
Anxiety  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  1/24 (4.17%) 
Confusional state  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  0/24 (0.00%) 
Insomnia  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Delirium  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Reproductive system and breast disorders         
Vaginal haemorrhage  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  2/24 (8.33%) 
Vulvovaginal pruritus  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  1/4 (25.00%)  1/19 (5.26%)  0/6 (0.00%)  3/24 (12.50%) 
Cough  1  0/4 (0.00%)  2/19 (10.53%)  1/6 (16.67%)  1/24 (4.17%) 
Oropharyngeal pain  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  1/24 (4.17%) 
Dyspnoea exertional  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  1/24 (4.17%) 
Nasal congestion  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Paranasal sinus hypersecretion  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  0/24 (0.00%) 
Pleural effusion  1  1/4 (25.00%)  0/19 (0.00%)  0/6 (0.00%)  0/24 (0.00%) 
Productive cough  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  1/4 (25.00%)  5/19 (26.32%)  1/6 (16.67%)  13/24 (54.17%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/4 (0.00%)  2/19 (10.53%)  1/6 (16.67%)  0/24 (0.00%) 
Rash macular  1  0/4 (0.00%)  2/19 (10.53%)  0/6 (0.00%)  1/24 (4.17%) 
Hyperhidrosis  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Palmar erythema  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  1/24 (4.17%) 
Pruritus generalised  1  1/4 (25.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Rash  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  1/24 (4.17%) 
Dry skin  1  0/4 (0.00%)  0/19 (0.00%)  1/6 (16.67%)  0/24 (0.00%) 
Night sweats  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Papule  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Rash generalised  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Skin disorder  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Skin lesion  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Urticaria  1  0/4 (0.00%)  1/19 (5.26%)  0/6 (0.00%)  0/24 (0.00%) 
Vascular disorders         
Hypertension  1  1/4 (25.00%)  0/19 (0.00%)  1/6 (16.67%)  2/24 (8.33%) 
Hypotension  1  0/4 (0.00%)  1/19 (5.26%)  1/6 (16.67%)  0/24 (0.00%) 
Raynaud's phenomenon  1  0/4 (0.00%)  0/19 (0.00%)  0/6 (0.00%)  2/24 (8.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT00962091     History of Changes
Other Study ID Numbers: C14010
U1111-1187-6657 ( Registry Identifier: WHO )
First Submitted: August 18, 2009
First Posted: August 19, 2009
Results First Submitted: June 12, 2018
Results First Posted: March 12, 2019
Last Update Posted: March 12, 2019