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Trial record 38 of 59 for:    MLN8237

Safety, Tolerability and Pharmacokinetic (PK) of Concomitant Esomeprazole and Rifampin, and QT Study on Single and Multiple-doses of Alisertib

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ClinicalTrials.gov Identifier: NCT01844583
Recruitment Status : Completed
First Posted : May 1, 2013
Results First Posted : March 25, 2019
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Solid Tumors
Lymphoma
Interventions Drug: Alisertib
Drug: Esomeprazole
Drug: Rifampin
Enrollment 55
Recruitment Details Participants took part in the study at 6 investigative sites in the United States from 25 June 2013 to 06 September 2016. Data cut-off for primary analysis was 04 August 2014.
Pre-assignment Details Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to receive alisertib 50 mg tablets, orally along with esomeprazole 40 mg, delayed release capsule once daily and alisertib 50 mg along with rifampin 600 mg capsule.
Arm/Group Title Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
Hide Arm/Group Description Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles). Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).
Period Title: Overall Study
Started 26 29
Completed 18 [1] 19
Not Completed 8 10
Reason Not Completed
Didn’t complete dosing;PK/ECG assessment             8             10
[1]
Completed=Completed protocol-specified dosing and PK/ECG assessment.
Arm/Group Title Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg Total
Hide Arm/Group Description Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles). Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles). Total of all reporting groups
Overall Number of Baseline Participants 26 29 55
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 29 participants 55 participants
62.2  (6.90) 60.4  (10.58) 61.3  (8.99)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 29 participants 55 participants
Female
14
  53.8%
21
  72.4%
35
  63.6%
Male
12
  46.2%
8
  27.6%
20
  36.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 29 participants 55 participants
Hispanic or Latino
3
  11.5%
4
  13.8%
7
  12.7%
Not Hispanic or Latino
22
  84.6%
24
  82.8%
46
  83.6%
Not Reported
1
   3.8%
1
   3.4%
2
   3.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 29 participants 55 participants
White
22
  84.6%
26
  89.7%
48
  87.3%
Black or African American
2
   7.7%
1
   3.4%
3
   5.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaska Native
1
   3.8%
1
   3.4%
2
   3.6%
Other
0
   0.0%
1
   3.4%
1
   1.8%
Not Reported
1
   3.8%
0
   0.0%
1
   1.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 26 participants 29 participants 55 participants
26
 100.0%
29
 100.0%
55
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 26 participants 29 participants 55 participants
166.6  (8.90) 164.8  (9.09) 165.7  (8.97)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 26 participants 29 participants 55 participants
82.07  (20.765) 77.37  (33.801) 79.59  (28.242)
Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 26 participants 29 participants 55 participants
29.557  (7.2787) 28.026  (9.4175) 28.750  (8.4327)
[1]
Measure Description: Body Mass Index = weight (kg)/ height (m^2).
1.Primary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) population included participants who completed the protocol-specified dosing and PK sampling requirements in cycle 1 and cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Esomeprazole Alisertib With Esomeprazole
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Esomeprazole 40 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 18 18
Mean (Standard Deviation)
Unit of Measure: nmol/L
1542.6  (357.19) 1804.8  (571.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Esomeprazole, Alisertib With Esomeprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 1.14
Confidence Interval (2-Sided) 90%
0.97 to 1.35
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
2.Primary Outcome
Title AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Esomeprazole Alisertib With Esomeprazole
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Esomeprazole 40 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 18 18
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
20427.8  (6813.46) 25094.4  (5574.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Esomeprazole, Alisertib With Esomeprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 90%
1.08 to 1.45
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
3.Primary Outcome
Title AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed protocol-specified dosing and PK sampling requirements in Cycle 1 and 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters. Here number of participants analyzed are participants who were evaluable for this outcome measure at specified time points.
Arm/Group Title Alisertib Without Esomeprazole Alisertib With Esomeprazole
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Esomeprazole 40 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
21371.4  (8138.55) 26612.5  (6626.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Esomeprazole, Alisertib With Esomeprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 1.28
Confidence Interval (2-Sided) 90%
1.07 to 1.53
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
4.Primary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Esomeprazole Alisertib With Esomeprazole
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Esomeprazole 40 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 18 18
Median (Full Range)
Unit of Measure: hours
4.0
(2 to 8)
3.0
(1 to 8)
5.Primary Outcome
Title Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Esomeprazole Alisertib With Esomeprazole
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Esomeprazole 40 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: hours
16.06  (5.398) 15.96  (5.234)
6.Primary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Rifampin Alisertib With Rifampin
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on up Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: nmol/L
1561.4  (661.81) 1581.5  (519.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Rifampin, Alisertib With Rifampin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 90%
0.84 to 1.26
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
7.Primary Outcome
Title AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Rifampin Alisertib With Rifampin
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on up Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
19732.0  (8489.24) 9470.5  (2653.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Rifampin, Alisertib With Rifampin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 0.51
Confidence Interval (2-Sided) 90%
0.41 to 0.62
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
8.Primary Outcome
Title AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed protocol-specified dosing and PK sampling requirements in Cycle 1 and 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters. Here number of participants analyzed are participants who were evaluable for this outcome measure at specified time points.
Arm/Group Title Alisertib Without Rifampin Alisertib With Rifampin
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on up Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 12 8
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
17258.3  (6163.60) 8955.0  (2389.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Rifampin, Alisertib With Rifampin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio
Estimated Value 0.53
Confidence Interval (2-Sided) 90%
0.41 to 0.70
Estimation Comments Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the esomeprazole effect and random terms for participants within sequence.
9.Primary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Rifampin Alisertib With Rifampin
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on up Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 20 20
Median (Full Range)
Unit of Measure: hours
4.0
(1 to 23)
2.1
(1 to 6)
10.Primary Outcome
Title Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
Arm/Group Title Alisertib Without Rifampin Alisertib With Rifampin
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.
Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on up Days 11 to 17 in Cycle 2.
Overall Number of Participants Analyzed 12 8
Mean (Standard Deviation)
Unit of Measure: hours
16.30  (6.608) 8.17  (5.476)
11.Primary Outcome
Title Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI)
Hide Description [Not Specified]
Time Frame Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.
Overall Number of Participants Analyzed 55
Mean (95% Confidence Interval)
Unit of Measure: milliseconds (msec)
Day 10, 0 hour postdose
-2.2 [1] 
(NA to 0.99)
Day 1, 0.5 hour postdose
-3.7 [1] 
(NA to -1.63)
Day 10, 0.5 hour postdose
-5.4 [1] 
(NA to -2.24)
Day 1, 1 hour postdose
-4.5 [1] 
(NA to -2.37)
Day 10, 1 hour postdose
-3.5 [1] 
(NA to -0.4)
Day 1, 2 hours postdose
-4.0 [1] 
(NA to -1.94)
Day 10, 2 hours postdose
-1.6 [1] 
(NA to 1.54)
Day 1, 3 hours postdose
-2.5 [1] 
(NA to -0.42)
Day 10, 3 hours postdose
-2.3 [1] 
(NA to 0.89)
Day 1, 4 hours postdose
-1.2 [1] 
(NA to 0.9)
Day 10, 4 hours postdose
-1.2 [1] 
(NA to 1.91)
Day 1, 6 hours postdose
-0.9 [1] 
(NA to 1.15)
Day 10, 6 hours postdose
-3.5 [1] 
(NA to -0.33)
Day 1, 8 hours postdose
-0.5 [1] 
(NA to 1.61)
Day 10, 8 hours postdose
-0.4 [1] 
(NA to 2.75)
Day 1, 10 hours postdose
-1.5 [1] 
(NA to 0.56)
Day 10, 10 hours postdose
-2.4 [1] 
(NA to 0.73)
Day 1, 24 hours postdose
-3.3 [1] 
(NA to -1.2)
[1]
One sided 95% Upper Confidence Bounds was estimated.
12.Secondary Outcome
Title Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF)
Hide Description [Not Specified]
Time Frame Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.
Overall Number of Participants Analyzed 55
Mean (95% Confidence Interval)
Unit of Measure: milliseconds (msec)
Day 10, 0 hour postdose
-2.4 [1] 
(NA to 0.7)
Day 1, 0.5 hour postdose
-3.9 [1] 
(NA to -1.8)
Day 10, 0.5 hour postdose
-5.3 [1] 
(NA to -2.19)
Day 1, 1 hour postdose
-4.6 [1] 
(NA to -2.54)
Day 10, 1 hour postdose
-3.9 [1] 
(NA to -0.76)
Day 1, 2 hours postdose
-3.5 [1] 
(NA to -1.51)
Day 10, 2 hours postdose
-2.5 [1] 
(NA to 0.63)
Day 1, 3 hours postdose
-2.1 [1] 
(NA to -0.09)
Day 10, 3 hours postdose
-2.6 [1] 
(NA to 0.55)
Day 1, 4 hours postdose
0 [1] 
(NA to 2.07)
Day 10, 4 hours postdose
-1.3 [1] 
(NA to 1.87)
Day 1, 6 hours postdose
-0.5 [1] 
(NA to 1.5)
Day 10, 6 hours postdose
-4.1 [1] 
(NA to -0.92)
Day 1, 8 hours postdose
0 [1] 
(NA to 2.1)
Day 10, 8 hours postdose
-1.6 [1] 
(NA to 1.54)
Day 1, 10 hours postdose
-1.2 [1] 
(NA to 0.9)
Day 10, 10 hours postdose
-3.5 [1] 
(NA to -0.3)
Day 1, 24 hours postdose
-3.8 [1] 
(NA to -1.72)
[1]
One sided 95% Upper Confidence Bounds was estimated.
13.Secondary 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 From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)
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Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of alisertib. According to the protocol analysis planned, primary purpose of the study was to observe the drug-drug interaction of either esomeprazole or rifampin on the single-dose of alisertib.
Arm/Group Title Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
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Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).
Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).
Overall Number of Participants Analyzed 26 29
Measure Type: Number
Unit of Measure: participants
AEs 25 27
SAEs 9 11
Time Frame From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)
Adverse Event Reporting Description Any AE spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. According to the protocol analysis planned, primary purpose of the study was to observe the drug-drug interaction of either esomeprazole or rifampin on the single-dose of alisertib.
 
Arm/Group Title Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
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Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.

Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2.

Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).

Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.

Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2.

Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).

All-Cause Mortality
Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   1/26 (3.85%)   3/29 (10.34%) 
Show Serious Adverse Events Hide Serious Adverse Events
Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   9/26 (34.62%)   11/29 (37.93%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  1/26 (3.85%)  0/29 (0.00%) 
Neutropenia  1  1/26 (3.85%)  0/29 (0.00%) 
Pancytopenia  1  1/26 (3.85%)  0/29 (0.00%) 
Gastrointestinal disorders     
Vomiting  1  1/26 (3.85%)  2/29 (6.90%) 
Nausea  1  0/26 (0.00%)  2/29 (6.90%) 
Abdominal pain  1  1/26 (3.85%)  1/29 (3.45%) 
Colitis  1  1/26 (3.85%)  0/29 (0.00%) 
Small intestinal obstruction  1  0/26 (0.00%)  1/29 (3.45%) 
Gastric ulcer perforation  1  0/26 (0.00%)  1/29 (3.45%) 
Ascites  1  1/26 (3.85%)  0/29 (0.00%) 
Hepatobiliary disorders     
Hepatic failure  1 [1]  0/26 (0.00%)  1/29 (3.45%) 
Infections and infestations     
Pyelonephritis  1  0/26 (0.00%)  1/29 (3.45%) 
Urinary tract infection  1  1/26 (3.85%)  0/29 (0.00%) 
Septic shock  1  1/26 (3.85%)  0/29 (0.00%) 
Injury, poisoning and procedural complications     
Hip fracture  1  1/26 (3.85%)  0/29 (0.00%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  0/26 (0.00%)  1/29 (3.45%) 
Dehydration  1  1/26 (3.85%)  0/29 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/26 (0.00%)  1/29 (3.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1 [1]  0/26 (0.00%)  1/29 (3.45%) 
Non-small cell lung cancer  1 [2]  1/26 (3.85%)  0/29 (0.00%) 
Pancreatic carcinoma metastatic  1 [1]  0/26 (0.00%)  1/29 (3.45%) 
Nervous system disorders     
Cerebrovascular accident  1  1/26 (3.85%)  0/29 (0.00%) 
Hepatic encephalopathy  1  0/26 (0.00%)  1/29 (3.45%) 
Neuropathy peripheral  1  1/26 (3.85%)  0/29 (0.00%) 
Psychiatric disorders     
Mental status changes  1  1/26 (3.85%)  0/29 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/26 (3.85%)  0/29 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/26 (3.85%)  1/29 (3.45%) 
Acute respiratory failure  1  1/26 (3.85%)  0/29 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/26 (0.00%)  2/29 (6.90%) 
Orthostatic hypotension  1  1/26 (3.85%)  0/29 (0.00%) 
1
Term from vocabulary, MedDRA, Version 19.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment with rifampin and alisertib and is not related.
[2]
One treatment-emergent death occurred during treatment with esomeprazole and alisertib and is not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Esomeprazole 40 mg + Alisertib 50 mg Rifampin 600 mg + Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   25/26 (96.15%)   25/29 (86.21%) 
Blood and lymphatic system disorders     
Neutropenia  1  10/26 (38.46%)  7/29 (24.14%) 
Anaemia  1  7/26 (26.92%)  8/29 (27.59%) 
Leukopenia  1  4/26 (15.38%)  6/29 (20.69%) 
Thrombocytopenia  1  5/26 (19.23%)  4/29 (13.79%) 
Lymphopenia  1  0/26 (0.00%)  3/29 (10.34%) 
Eye disorders     
Vision blurred  1  2/26 (7.69%)  2/29 (6.90%) 
Gastrointestinal disorders     
Diarrhoea  1  15/26 (57.69%)  4/29 (13.79%) 
Stomatitis  1  11/26 (42.31%)  6/29 (20.69%) 
Vomiting  1  7/26 (26.92%)  5/29 (17.24%) 
Nausea  1  7/26 (26.92%)  4/29 (13.79%) 
Abdominal pain  1  4/26 (15.38%)  5/29 (17.24%) 
Constipation  1  4/26 (15.38%)  1/29 (3.45%) 
Dry mouth  1  3/26 (11.54%)  1/29 (3.45%) 
Dyspepsia  1  3/26 (11.54%)  1/29 (3.45%) 
General disorders     
Fatigue  1  12/26 (46.15%)  10/29 (34.48%) 
Oedema peripheral  1  2/26 (7.69%)  3/29 (10.34%) 
Asthenia  1  3/26 (11.54%)  0/29 (0.00%) 
Pyrexia  1  2/26 (7.69%)  1/29 (3.45%) 
Non-cardiac chest pain  1  0/26 (0.00%)  2/29 (6.90%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  2/26 (7.69%)  1/29 (3.45%) 
Infections and infestations     
Upper respiratory tract infection  1  3/26 (11.54%)  0/29 (0.00%) 
Urinary tract infection  1  1/26 (3.85%)  2/29 (6.90%) 
Injury, poisoning and procedural complications     
Fall  1  2/26 (7.69%)  0/29 (0.00%) 
Investigations     
Gamma-glutamyltransferase increased  1  3/26 (11.54%)  4/29 (13.79%) 
Alanine aminotransferase increased  1  3/26 (11.54%)  1/29 (3.45%) 
Aspartate aminotransferase increased  1  2/26 (7.69%)  2/29 (6.90%) 
Weight decreased  1  3/26 (11.54%)  1/29 (3.45%) 
Metabolism and nutrition disorders     
Decreased appetite  1  7/26 (26.92%)  3/29 (10.34%) 
Dehydration  1  4/26 (15.38%)  3/29 (10.34%) 
Hypokalaemia  1  5/26 (19.23%)  2/29 (6.90%) 
Hypomagnesaemia  1  2/26 (7.69%)  2/29 (6.90%) 
Hypophosphataemia  1  3/26 (11.54%)  0/29 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  4/26 (15.38%)  3/29 (10.34%) 
Arthralgia  1  5/26 (19.23%)  0/29 (0.00%) 
Bone pain  1  3/26 (11.54%)  0/29 (0.00%) 
Musculoskeletal chest pain  1  2/26 (7.69%)  1/29 (3.45%) 
Pain in extremity  1  2/26 (7.69%)  1/29 (3.45%) 
Nervous system disorders     
Dizziness  1  3/26 (11.54%)  1/29 (3.45%) 
Headache  1  2/26 (7.69%)  2/29 (6.90%) 
Peripheral sensory neuropathy  1  1/26 (3.85%)  2/29 (6.90%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/26 (7.69%)  5/29 (17.24%) 
Nasal congestion  1  4/26 (15.38%)  0/29 (0.00%) 
Oropharyngeal pain  1  2/26 (7.69%)  1/29 (3.45%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  14/26 (53.85%)  6/29 (20.69%) 
Pruritus  1  4/26 (15.38%)  3/29 (10.34%) 
Rash  1  1/26 (3.85%)  2/29 (6.90%) 
Rash macular  1  3/26 (11.54%)  0/29 (0.00%) 
Rash maculo-papular  1  2/26 (7.69%)  0/29 (0.00%) 
1
Term from vocabulary, MedDRA, Version 19.0
Indicates events were collected by systematic assessment
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: NCT01844583     History of Changes
Other Study ID Numbers: C14015
First Submitted: April 29, 2013
First Posted: May 1, 2013
Results First Submitted: April 9, 2018
Results First Posted: March 25, 2019
Last Update Posted: March 25, 2019