Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetic (PK) of Concomitant Esomeprazole and Rifampin, and QT Study on Single and Multiple-doses of Alisertib (NCT NCT01844583)

NCT ID: NCT01844583

Last Updated: 2019-03-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 55 participants
• Primary outcome timeframe: 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
• Results posted on: 2019-03-25

Participant Flow

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.

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.

Participant milestones

Measure	Esomeprazole 40 mg + Alisertib 50 mg 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).	Rifampin 600 mg + Alisertib 50 mg 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 Study STARTED	26	29
Overall Study COMPLETED	18	19
Overall Study NOT COMPLETED	8	10

Reasons for withdrawal

Measure	Esomeprazole 40 mg + Alisertib 50 mg 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).	Rifampin 600 mg + Alisertib 50 mg 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 Study Didn't complete dosing;PK/ECG assessment	8	10

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Esomeprazole 40 mg + Alisertib 50 mg n=26 Participants 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).	Rifampin 600 mg + Alisertib 50 mg n=29 Participants 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 n=55 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 6.90 • n=5 Participants	60.4 years STANDARD_DEVIATION 10.58 • n=7 Participants	61.3 years STANDARD_DEVIATION 8.99 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	22 Participants n=5 Participants	26 Participants n=7 Participants	48 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Height	166.6 cm STANDARD_DEVIATION 8.90 • n=5 Participants	164.8 cm STANDARD_DEVIATION 9.09 • n=7 Participants	165.7 cm STANDARD_DEVIATION 8.97 • n=5 Participants
Weight	82.07 kg STANDARD_DEVIATION 20.765 • n=5 Participants	77.37 kg STANDARD_DEVIATION 33.801 • n=7 Participants	79.59 kg STANDARD_DEVIATION 28.242 • n=5 Participants
Body Mass Index	29.557 kg/m^2 STANDARD_DEVIATION 7.2787 • n=5 Participants	28.026 kg/m^2 STANDARD_DEVIATION 9.4175 • n=7 Participants	28.750 kg/m^2 STANDARD_DEVIATION 8.4327 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=18 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=18 Participants 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.
Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole	1542.6 nmol/L Standard Deviation 357.19	1804.8 nmol/L Standard Deviation 571.89

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=18 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=18 Participants 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.
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	20427.8 hr*nmol/L Standard Deviation 6813.46	25094.4 hr*nmol/L Standard Deviation 5574.04

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=14 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=16 Participants 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.
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole	21371.4 hr*nmol/L Standard Deviation 8138.55	26612.5 hr*nmol/L Standard Deviation 6626.40

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=18 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=18 Participants 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.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole	4.0 hours Interval 2.0 to 8.0	3.0 hours Interval 1.0 to 8.0

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=14 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=16 Participants 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.
Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole	16.06 hours Standard Deviation 5.398	15.96 hours Standard Deviation 5.234

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=20 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=20 Participants 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.
Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin	1561.4 nmol/L Standard Deviation 661.81	1581.5 nmol/L Standard Deviation 519.68

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=20 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=20 Participants 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.
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	19732.0 hr*nmol/L Standard Deviation 8489.24	9470.5 hr*nmol/L Standard Deviation 2653.60

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=12 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=8 Participants 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.
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin	17258.3 hr*nmol/L Standard Deviation 6163.60	8955.0 hr*nmol/L Standard Deviation 2389.25

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=20 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=20 Participants 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.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin	4.0 hours Interval 1.0 to 23.0	2.1 hours Interval 1.0 to 6.0

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=12 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=8 Participants 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.
Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin	16.30 hours Standard Deviation 6.608	8.17 hours Standard Deviation 5.476

PRIMARY outcome

Timeframe: Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1

Population: The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.

Outcome measures

Measure	Alisertib Without Esomeprazole n=55 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole 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.
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 8 hours postdose	-0.5 milliseconds (msec) Interval to 1.61 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 0 hour postdose	-2.2 milliseconds (msec) Interval to 0.99 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 0.5 hour postdose	-3.7 milliseconds (msec) Interval to -1.63 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 0.5 hour postdose	-5.4 milliseconds (msec) Interval to -2.24 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 1 hour postdose	-4.5 milliseconds (msec) Interval to -2.37 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 1 hour postdose	-3.5 milliseconds (msec) Interval to -0.4 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 2 hours postdose	-4.0 milliseconds (msec) Interval to -1.94 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 2 hours postdose	-1.6 milliseconds (msec) Interval to 1.54 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 3 hours postdose	-2.5 milliseconds (msec) Interval to -0.42 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 3 hours postdose	-2.3 milliseconds (msec) Interval to 0.89 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 4 hours postdose	-1.2 milliseconds (msec) Interval to 0.9 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 4 hours postdose	-1.2 milliseconds (msec) Interval to 1.91 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 6 hours postdose	-0.9 milliseconds (msec) Interval to 1.15 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 6 hours postdose	-3.5 milliseconds (msec) Interval to -0.33 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 8 hours postdose	-0.4 milliseconds (msec) Interval to 2.75 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 10 hours postdose	-1.5 milliseconds (msec) Interval to 0.56 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 10, 10 hours postdose	-2.4 milliseconds (msec) Interval to 0.73 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) Day 1, 24 hours postdose	-3.3 milliseconds (msec) Interval to -1.2 One sided 95% Upper Confidence Bounds was estimated.	—

SECONDARY outcome

Timeframe: Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1

Population: The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.

Outcome measures

Measure	Alisertib Without Esomeprazole n=55 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole 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.
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 0 hour postdose	-2.4 milliseconds (msec) Interval to 0.7 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 0.5 hour postdose	-3.9 milliseconds (msec) Interval to -1.8 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 0.5 hour postdose	-5.3 milliseconds (msec) Interval to -2.19 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 1 hour postdose	-4.6 milliseconds (msec) Interval to -2.54 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 1 hour postdose	-3.9 milliseconds (msec) Interval to -0.76 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 2 hours postdose	-3.5 milliseconds (msec) Interval to -1.51 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 2 hours postdose	-2.5 milliseconds (msec) Interval to 0.63 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 3 hours postdose	-2.1 milliseconds (msec) Interval to -0.09 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 3 hours postdose	-2.6 milliseconds (msec) Interval to 0.55 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 4 hours postdose	0 milliseconds (msec) Interval to 2.07 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 4 hours postdose	-1.3 milliseconds (msec) Interval to 1.87 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 6 hours postdose	-0.5 milliseconds (msec) Interval to 1.5 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 6 hours postdose	-4.1 milliseconds (msec) Interval to -0.92 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 8 hours postdose	0 milliseconds (msec) Interval to 2.1 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 8 hours postdose	-1.6 milliseconds (msec) Interval to 1.54 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 10 hours postdose	-1.2 milliseconds (msec) Interval to 0.9 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 10, 10 hours postdose	-3.5 milliseconds (msec) Interval to -0.3 One sided 95% Upper Confidence Bounds was estimated.	—
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) Day 1, 24 hours postdose	-3.8 milliseconds (msec) Interval to -1.72 One sided 95% Upper Confidence Bounds was estimated.	—

SECONDARY outcome

Timeframe: From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)

Population: 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.

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.

Outcome measures

Measure	Alisertib Without Esomeprazole n=26 Participants Alisertib 50 mg, tablets, orally, once on Day 1 in Cycle 1.	Alisertib With Esomeprazole n=29 Participants 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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	25 participants	27 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	9 participants	11 participants

Adverse Events

Esomeprazole 40 mg + Alisertib 50 mg

Serious events: 9 serious events

Other events: 25 other events

Deaths: 1 deaths

Rifampin 600 mg + Alisertib 50 mg

Serious events: 11 serious events

Other events: 25 other events

Deaths: 3 deaths

Serious adverse events

Measure	Esomeprazole 40 mg + Alisertib 50 mg n=26 participants at risk 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).	Rifampin 600 mg + Alisertib 50 mg n=29 participants at risk 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).
Gastrointestinal disorders Ascites	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Infections and infestations Pyelonephritis	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Vomiting	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Nausea	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Abdominal pain	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Colitis	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Infections and infestations Urinary tract infection	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Infections and infestations Septic shock	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Cerebrovascular accident	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Hepatic encephalopathy	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Neuropathy peripheral	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Vascular disorders Deep vein thrombosis	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Vascular disorders Orthostatic hypotension	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Febrile neutropenia	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Neutropenia	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Pancytopenia	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Dehydration	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Hepatobiliary disorders Hepatic failure	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Injury, poisoning and procedural complications Hip fracture	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Psychiatric disorders Mental status changes	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Renal and urinary disorders Acute kidney injury	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.

Other adverse events

Measure	Esomeprazole 40 mg + Alisertib 50 mg n=26 participants at risk 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).	Rifampin 600 mg + Alisertib 50 mg n=29 participants at risk 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).
Skin and subcutaneous tissue disorders Pruritus	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Diarrhoea	57.7% 15/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	13.8% 4/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Stomatitis	42.3% 11/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	20.7% 6/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Vomiting	26.9% 7/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	17.2% 5/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Nausea	26.9% 7/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	13.8% 4/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Abdominal pain	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	17.2% 5/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Constipation	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Dry mouth	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Gastrointestinal disorders Dyspepsia	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
General disorders Fatigue	46.2% 12/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	34.5% 10/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
General disorders Oedema peripheral	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
General disorders Asthenia	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
General disorders Pyrexia	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
General disorders Non-cardiac chest pain	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Skin and subcutaneous tissue disorders Alopecia	53.8% 14/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	20.7% 6/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Skin and subcutaneous tissue disorders Rash	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Skin and subcutaneous tissue disorders Rash macular	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Neutropenia	38.5% 10/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	24.1% 7/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Anaemia	26.9% 7/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	27.6% 8/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Leukopenia	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	20.7% 6/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Thrombocytopenia	19.2% 5/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	13.8% 4/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Decreased appetite	26.9% 7/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Dehydration	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Hypokalaemia	19.2% 5/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Hypomagnesaemia	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Metabolism and nutrition disorders Hypophosphataemia	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Back pain	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	10.3% 3/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Arthralgia	19.2% 5/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Bone pain	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Investigations Gamma-glutamyltransferase increased	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	13.8% 4/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Investigations Alanine aminotransferase increased	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Investigations Aspartate aminotransferase increased	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Investigations Weight decreased	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	17.2% 5/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Respiratory, thoracic and mediastinal disorders Nasal congestion	15.4% 4/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Dizziness	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Headache	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Nervous system disorders Peripheral sensory neuropathy	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Infections and infestations Upper respiratory tract infection	11.5% 3/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Infections and infestations Urinary tract infection	3.8% 1/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Eye disorders Vision blurred	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	6.9% 2/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Hepatobiliary disorders Hyperbilirubinaemia	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	3.4% 1/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.
Injury, poisoning and procedural complications Fall	7.7% 2/26 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.	0.00% 0/29 • From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER