Food Effect Study of Alisertib (MLN8237) in Participants With Advanced Solid Tumors or Lymphomas

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01898078
• Collaborator: (none)
• Enrollment: 26
• Locations: 3
• Arms: 2
• Actual Duration (Months): 42.3
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of food on the single-dose pharmacokinetics (PK) of alisertib administered as an enteric-coated tablet (ECT) formulation in participants with advanced solid tumors or lymphomas.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors; Lymphoma	Drug: Alisertib	Phase 1

Detailed Description

The drug being tested in this study is called alisertib. Alisertib is being tested in adult participants with advanced solid tumors or lymphomas.

The study enrolled 26 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Alisertib 50 mg Fed + Fasted

• Alisertib 50 mg Fasted + Fed

All participants will be asked to take one alisertib tablet (ECT), orally, with or without a standard high-fat breakfast Cycle 1, Day 1, with the respective alternate food intake condition (fasted to fed or fed to fasted) on Cycle 2, Day 1, each followed by 14-day rest period. Participants will take alisertib, ECT, orally BID on Days 4 to 10 of Cycles 1 and 2, each followed by 14-day rest period. From Cycle 3 onwards participants will continue taking alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity.

This multi-center trial conducted at 3 sites in the United States. Participants will make multiple visits to the clinic and plus a final visit after 30 days of receiving their last dose of drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Phase 1, Two-Way, Cross-Over Study of the Effect of the Food on the Pharmacokinetics of MLN8237 (Alisertib) in Patients With Advanced Solid Tumors or Lymphomas
• Actual Study Start Date: Jul 16, 2013
• Actual Primary Completion Date: Mar 5, 2014
• Actual Study Completion Date: Jan 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alisertib 50 mg Fed + Fasted Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Drug: Alisertib; Alisertib ECT; Other Names: MLN8237
Experimental: Alisertib 50 mg Fasted + Fed Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Drug: Alisertib; Alisertib ECT; Other Names: MLN8237

Outcome Measures

Primary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration of Alisertib [Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]

2. AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib [Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]

3. AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib [Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]

Secondary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose through 30 days after the last dose of study drug (up to 225 days)]

   An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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.

2. Number of Participants With Clinically Significant Change in Laboratory Parameters Reported as AEs [From first dose through 30 days after the last dose of study drug (up to 225 days)]

   The number of participants with any clinical significant change in safety laboratory values collected throughout the study.

3. Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs [From first dose through 30 days after the last dose of study drug (up to 225 days)]

   The number of participants with any clinical significant change in vital signs (sitting diastolic and systolic blood pressure, heart rate, and temperature) were collected throughout the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years or older

• Histologically or cytologically confirmed advanced tumors or lymphomas for which standard curative or life-prolonging treatment does not exist, or is no longer effective or tolerable

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Participant must meet protocol-specified laboratory values

• Suitable venous access

• Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time or agree to practice true abstinence

• Male participants who agree to practice effective barrier contraception during the entire study and through 4 months after the last dose of study drug OR agree to practice true abstinence

Exclusion Criteria:

• Prior or current investigational therapies within 4 weeks before the first dose of alisertib

• Female participants who are lactating or pregnant

• Participant requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib and during the study

• Medical conditions requiring daily, chronic, or regular use of proton pump inhibitors (PPIs) within 7 days preceding the first dose of alisertib, or histamine (H2)-receptor antagonists

• Participant requiring systemic anticoagulation

• Ongoing nausea or vomiting that is Grade 2 or worse in intensity

• Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption, excretion, or tolerance of alisertib

• History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease

• Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection

• Participant who are lactose-intolerant or are unwilling/unable to consume the protocol specified standardized high-fat breakfast

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bronx	New York	United States
2		Nashville	Tennessee	United States
3		San Antonio	Texas	United States

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01898078
• Other Study ID Numbers: C14017
• First Posted: Jul 12, 2013
• Last Update Posted: Jun 21, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Millennium Pharmaceuticals, Inc.: MLN8237; Alisertib; Food effects
• Additional relevant MeSH terms: Lymphoma

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 3 investigative sites in the United States from 16 July 2013 to 24 January 2017. Data cut-off for the primary analysis was 05 March 2014.
Pre-assignment Detail	Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to crossover fashion to receive alisertib 50 mg enteric-coated tablet (ECT), orally in fasted or fed state in Cycles 1 and 2.

Arm/Group Title	Alisertib 50 mg Fed + Fasted	Alisertib 50 mg Fasted + Fed
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
Period Title: Overall Study
STARTED	13	13
COMPLETED	7	5
NOT COMPLETED	6	8

Baseline Characteristics

Arm/Group Title	Alisertib 50 mg Fed + Fasted	Alisertib 50 mg Fasted + Fed	Total
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Total of all reporting groups
Overall Participants	13	13	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.6 (10.15)	61.7 (12.64)	60.7 (11.28)
Sex: Female, Male (Count of Participants)
Female	6 46.2%	7 53.8%	13 50%
Male	7 53.8%	6 46.2%	13 50%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	5 38.5%	4 30.8%	9 34.6%
Not Hispanic or Latino	8 61.5%	9 69.2%	17 65.4%
Race/Ethnicity, Customized (Count of Participants)
White	10 76.9%	13 100%	23 88.5%
Black or African American	3 23.1%	0 0%	3 11.5%
Region of Enrollment (Count of Participants)
United States	13 100%	13 100%	26 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.9 (14.34)	165.3 (11.32)	166.1 (12.68)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.59 (15.484)	78.37 (20.183)	75.98 (17.792)

Outcome Measures

1. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration of Alisertib
Time Frame	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants with sufficient dosing data and PK concentration-time data to reliably estimate the PK parameters.

Arm/Group Title	Alisertib 50 mg Fed	Alisertib 50 mg Fasted
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1 in Cycles 1 and 2.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1 in Cycles 1 and 2.
Measure Participants	22	22
Mean (Standard Deviation) [nM]	1338.6 (487.25)	1354.5 (432.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alisertib 50 mg Fed, Alisertib 50 mg Fasted
	Comments	The confidence intervals are calculated for the difference in the LS means of the ln-transformed Cmax plain values (difference = Fed/Fasted). Antilogs of the confidence limits for the difference are taken to construct the confidence intervals for the ratio of the geometric means.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 90%; 0.85 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the treatment effect, sequence effect, period effect and random terms for participants within sequence.

2. Primary Outcome

Title	AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib
Time Frame	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK population included participants with sufficient dosing data and PK concentration-time data to reliably estimate the PK parameters.

Arm/Group Title	Alisertib 50 mg Fed	Alisertib 50 mg Fasted
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1 in Cycles 1 and 2.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1 in Cycles 1 and 2.
Measure Participants	22	22
Mean (Standard Deviation) [hr*nM]	24645.5 (12467.39)	20797.7 (8847.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alisertib 50 mg Fed, Alisertib 50 mg Fasted
	Comments	The confidence intervals are calculated for the difference in the LS means of the ln-transformed AUC(last) plain values (difference = Fed/Fasted). Antilogs of the confidence limits for the difference are taken to construct the confidence intervals for the ratio of the geometric mean.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Ratio
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 90%; 1.01 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates for each PK parameter were obtained using a mixed effects model of log (PK parameter) with fixed terms for the treatment effect, sequence effect, period effect and random terms for participants within sequence.

3. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib
Time Frame	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK population included participants with sufficient dosing data and PK concentration-time data to reliably estimate the PK parameters. Here, number of participants analysed are the participants who were evaluable for this outcome measure.

Arm/Group Title	Alisertib 50 mg Fed	Alisertib 50 mg Fasted
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1 in Cycles 1 and 2.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1 in Cycles 1 and 2.
Measure Participants	16	14
Mean (Standard Deviation) [hr*nM]	24537.5 (9882.10)	22771.4 (10206.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alisertib 50 mg Fed, Alisertib 50 mg Fasted
	Comments	The confidence intervals are calculated for the difference in the LS means of the ln-transformed AUC∞ plain values (difference = Fed/Fasted). Antilogs of the confidence limits for the difference are taken to construct the confidence intervals for the ratio of the geometric mean
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Ratio
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 90%; 0.96 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates for each PK parameter were obtained using a mixed effects model of log(PK parameter) with fixed terms for the treatment effect, sequence effect, period effect and random terms for participants within sequence.

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame	From first dose through 30 days after the last dose of study drug (up to 225 days)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least one dose of study drug. According to the protocol analysis planned, data for the safety and tolerability was collected as per the treatment sequence received in the study, irrespective of the fed or fasted condition.

Arm/Group Title	Alisertib 50 mg Fed + Fasted	Alisertib 50 mg Fasted + Fed
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
Measure Participants	13	13
AEs	13 100%	13 100%
SAEs	7 53.8%	7 53.8%

5. Secondary Outcome

Title	Number of Participants With Clinically Significant Change in Laboratory Parameters Reported as AEs
Description	The number of participants with any clinical significant change in safety laboratory values collected throughout the study.
Time Frame	From first dose through 30 days after the last dose of study drug (up to 225 days)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least one dose of study drug. According to the protocol analysis planned, data for the safety and tolerability was collected as per the treatment sequence received in the study, irrespective of the fed or fasted condition.

Arm/Group Title	Alisertib 50 mg Fed + Fasted	Alisertib 50 mg Fasted + Fed
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
Measure Participants	13	13
Neutropenia	10 76.9%	8 61.5%
Anaemia	5 38.5%	3 23.1%
Leukopenia	5 38.5%	2 15.4%
Thrombocytopenia	1 7.7%	2 15.4%
Hypokalaemia	0 0%	3 23.1%
Hyperbilirubinaemia	1 7.7%	1 7.7%
Neutrophil count decreased	1 7.7%	1 7.7%
Lymphopenia	0 0%	1 7.7%
Hyperkalaemia	1 7.7%	0 0%
Hypomagnesaemia	0 0%	1 7.7%
Aspartate aminotransferase increased	0 0%	1 7.7%
Blood bilirubin increased	1 7.7%	0 0%

6. Secondary Outcome

Title	Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
Description	The number of participants with any clinical significant change in vital signs (sitting diastolic and systolic blood pressure, heart rate, and temperature) were collected throughout the study.
Time Frame	From first dose through 30 days after the last dose of study drug (up to 225 days)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least one dose of study drug. According to the protocol analysis planned, data for the safety and tolerability was collected as per the treatment sequence received in the study, irrespective of the fed or fasted condition.

Arm/Group Title	Alisertib 50 mg Fed + Fasted	Alisertib 50 mg Fasted + Fed
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
Measure Participants	13	13
Hypertension	0 0%	1 7.7%
Hypotension	0 0%	1 7.7%
Tachycardia	0 0%	1 7.7%

Adverse Events

Time Frame	From first dose through 30 days after the last dose of study drug (up to 225 days)
Adverse Event Reporting Description	According to the protocol analysis planned, data for the safety and tolerability was collected as per the treatment sequence received in the study, irrespective of the fed or fasted condition.
Arm/Group Title	Alisertib 50 mg Fed + Fasted		Alisertib 50 mg Fasted + Fed
Arm/Group Description	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.		Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
All Cause Mortality
	Alisertib 50 mg Fed + Fasted		Alisertib 50 mg Fasted + Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		1/13 (7.7%)
Serious Adverse Events
	Alisertib 50 mg Fed + Fasted		Alisertib 50 mg Fasted + Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/13 (53.8%)		7/13 (53.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/13 (7.7%)		0/13 (0%)
Gastrointestinal disorders
Abdominal pain	2/13 (15.4%)		1/13 (7.7%)
Rectal haemorrhage	0/13 (0%)		1/13 (7.7%)
Nausea	0/13 (0%)		1/13 (7.7%)
Vomiting	0/13 (0%)		1/13 (7.7%)
General disorders
Pyrexia	1/13 (7.7%)		0/13 (0%)
Non-cardiac chest pain	0/13 (0%)		1/13 (7.7%)
Infections and infestations
Cellulitis	0/13 (0%)		1/13 (7.7%)
Bacteraemia	1/13 (7.7%)		0/13 (0%)
Pneumonia streptococcal	1/13 (7.7%)		0/13 (0%)
Pyelonephritis	0/13 (0%)		1/13 (7.7%)
Streptococcal sepsis	1/13 (7.7%)		0/13 (0%)
Injury, poisoning and procedural complications
Pneumothorax traumatic	1/13 (7.7%)		0/13 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/13 (0%)		1/13 (7.7%)
Back pain	0/13 (0%)		1/13 (7.7%)
Nervous system disorders
Toxic encephalopathy	1/13 (7.7%)		0/13 (0%)
Psychiatric disorders
Delirium	0/13 (0%)		1/13 (7.7%)
Mental status changes	1/13 (7.7%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/13 (7.7%)		0/13 (0%)
Pulmonary embolism	0/13 (0%)		1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Alisertib 50 mg Fed + Fasted		Alisertib 50 mg Fasted + Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		13/13 (100%)
Blood and lymphatic system disorders
Neutropenia	11/13 (84.6%)		8/13 (61.5%)
Anaemia	6/13 (46.2%)		4/13 (30.8%)
Leukopenia	5/13 (38.5%)		3/13 (23.1%)
Thrombocytopenia	2/13 (15.4%)		3/13 (23.1%)
Lymphopenia	0/13 (0%)		1/13 (7.7%)
Cardiac disorders
Tachycardia	0/13 (0%)		1/13 (7.7%)
Ear and labyrinth disorders
Ear pain	0/13 (0%)		1/13 (7.7%)
Hypoacusis	0/13 (0%)		1/13 (7.7%)
Eye disorders
Cataract	2/13 (15.4%)		0/13 (0%)
Eyelid cyst	1/13 (7.7%)		0/13 (0%)
Gastrointestinal disorders
Stomatitis	3/13 (23.1%)		8/13 (61.5%)
Vomiting	3/13 (23.1%)		7/13 (53.8%)
Diarrhoea	5/13 (38.5%)		4/13 (30.8%)
Nausea	2/13 (15.4%)		5/13 (38.5%)
Abdominal pain	2/13 (15.4%)		2/13 (15.4%)
Abdominal pain upper	0/13 (0%)		3/13 (23.1%)
Abdominal pain lower	1/13 (7.7%)		1/13 (7.7%)
Constipation	1/13 (7.7%)		1/13 (7.7%)
Dysphagia	1/13 (7.7%)		1/13 (7.7%)
Gastrooesophageal reflux disease	0/13 (0%)		2/13 (15.4%)
Abdominal distension	0/13 (0%)		1/13 (7.7%)
Ascites	0/13 (0%)		1/13 (7.7%)
Diverticulum	0/13 (0%)		1/13 (7.7%)
Dry mouth	0/13 (0%)		1/13 (7.7%)
Faeces discoloured	0/13 (0%)		1/13 (7.7%)
Haematemesis	0/13 (0%)		1/13 (7.7%)
Haemorrhoids	0/13 (0%)		1/13 (7.7%)
Inguinal hernia	1/13 (7.7%)		0/13 (0%)
Oesophageal stenosis	0/13 (0%)		1/13 (7.7%)
Swollen tongue	0/13 (0%)		1/13 (7.7%)
General disorders
Fatigue	8/13 (61.5%)		3/13 (23.1%)
Pyrexia	1/13 (7.7%)		5/13 (38.5%)
Asthenia	1/13 (7.7%)		3/13 (23.1%)
Oedema peripheral	1/13 (7.7%)		2/13 (15.4%)
Chills	1/13 (7.7%)		1/13 (7.7%)
Local swelling	2/13 (15.4%)		0/13 (0%)
Catheter site erythema	1/13 (7.7%)		0/13 (0%)
Catheter site haemorrhage	1/13 (7.7%)		0/13 (0%)
Catheter site pain	1/13 (7.7%)		0/13 (0%)
Infusion site vesicles	1/13 (7.7%)		0/13 (0%)
Localised oedema	0/13 (0%)		1/13 (7.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/13 (7.7%)		1/13 (7.7%)
Infections and infestations
Urinary tract infection	2/13 (15.4%)		1/13 (7.7%)
Sinusitis	1/13 (7.7%)		1/13 (7.7%)
Bronchitis	0/13 (0%)		1/13 (7.7%)
Candida infection	0/13 (0%)		1/13 (7.7%)
Cystitis	0/13 (0%)		1/13 (7.7%)
Genital herpes	0/13 (0%)		1/13 (7.7%)
Lung abscess	1/13 (7.7%)		0/13 (0%)
Nasopharyngitis	0/13 (0%)		1/13 (7.7%)
Oral candidiasis	0/13 (0%)		1/13 (7.7%)
Oral herpes	0/13 (0%)		1/13 (7.7%)
Upper respiratory tract infection	0/13 (0%)		1/13 (7.7%)
Vaginitis bacterial	0/13 (0%)		1/13 (7.7%)
Injury, poisoning and procedural complications
Fall	2/13 (15.4%)		2/13 (15.4%)
Contusion	1/13 (7.7%)		1/13 (7.7%)
Femur fracture	1/13 (7.7%)		0/13 (0%)
Fibula fracture	0/13 (0%)		1/13 (7.7%)
Ligament sprain	0/13 (0%)		1/13 (7.7%)
Investigations
Aspartate aminotransferase increased	1/13 (7.7%)		1/13 (7.7%)
Neutrophil count decreased	1/13 (7.7%)		1/13 (7.7%)
Alanine aminotransferase increased	1/13 (7.7%)		0/13 (0%)
Blood bilirubin increased	1/13 (7.7%)		0/13 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/13 (23.1%)		4/13 (30.8%)
Dehydration	1/13 (7.7%)		2/13 (15.4%)
Hypokalaemia	0/13 (0%)		3/13 (23.1%)
Hypomagnesaemia	1/13 (7.7%)		1/13 (7.7%)
Hyperglycaemia	1/13 (7.7%)		0/13 (0%)
Hyperkalaemia	1/13 (7.7%)		0/13 (0%)
Hypoalbuminaemia	0/13 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	2/13 (15.4%)		2/13 (15.4%)
Musculoskeletal chest pain	2/13 (15.4%)		1/13 (7.7%)
Pain in extremity	2/13 (15.4%)		1/13 (7.7%)
Arthralgia	0/13 (0%)		2/13 (15.4%)
Joint swelling	1/13 (7.7%)		1/13 (7.7%)
Muscle spasms	2/13 (15.4%)		0/13 (0%)
Musculoskeletal pain	1/13 (7.7%)		1/13 (7.7%)
Myalgia	0/13 (0%)		2/13 (15.4%)
Costochondritis	1/13 (7.7%)		0/13 (0%)
Flank pain	0/13 (0%)		1/13 (7.7%)
Groin pain	1/13 (7.7%)		0/13 (0%)
Inguinal mass	0/13 (0%)		1/13 (7.7%)
Muscular weakness	1/13 (7.7%)		0/13 (0%)
Neck pain	0/13 (0%)		1/13 (7.7%)
Nervous system disorders
Dizziness	2/13 (15.4%)		3/13 (23.1%)
Headache	1/13 (7.7%)		2/13 (15.4%)
Somnolence	2/13 (15.4%)		1/13 (7.7%)
Neuropathy peripheral	2/13 (15.4%)		0/13 (0%)
Memory impairment	1/13 (7.7%)		0/13 (0%)
Metabolic encephalopathy	1/13 (7.7%)		0/13 (0%)
Peripheral sensory neuropathy	1/13 (7.7%)		0/13 (0%)
Psychiatric disorders
Confusional state	2/13 (15.4%)		2/13 (15.4%)
Anxiety	1/13 (7.7%)		0/13 (0%)
Hallucination	1/13 (7.7%)		0/13 (0%)
Hallucination, auditory	0/13 (0%)		1/13 (7.7%)
Insomnia	1/13 (7.7%)		0/13 (0%)
Mental status changes	0/13 (0%)		1/13 (7.7%)
Renal and urinary disorders
Pollakiuria	1/13 (7.7%)		1/13 (7.7%)
Urinary incontinence	0/13 (0%)		2/13 (15.4%)
Micturition urgency	0/13 (0%)		1/13 (7.7%)
Urinary hesitation	1/13 (7.7%)		0/13 (0%)
Reproductive system and breast disorders
Vaginal discharge	1/13 (7.7%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	2/13 (15.4%)		3/13 (23.1%)
Dyspnoea exertional	1/13 (7.7%)		3/13 (23.1%)
Sinus congestion	1/13 (7.7%)		3/13 (23.1%)
Oropharyngeal pain	2/13 (15.4%)		1/13 (7.7%)
Dyspnoea	1/13 (7.7%)		1/13 (7.7%)
Nasal congestion	1/13 (7.7%)		1/13 (7.7%)
Epistaxis	0/13 (0%)		1/13 (7.7%)
Haemoptysis	1/13 (7.7%)		0/13 (0%)
Lung infiltration	0/13 (0%)		1/13 (7.7%)
Paranasal sinus discomfort	0/13 (0%)		1/13 (7.7%)
Productive cough	0/13 (0%)		1/13 (7.7%)
Rhinorrhoe	0/13 (0%)		1/13 (7.7%)
Throat irritation	1/13 (7.7%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Alopecia	8/13 (61.5%)		7/13 (53.8%)
Rash	1/13 (7.7%)		2/13 (15.4%)
Erythema	1/13 (7.7%)		1/13 (7.7%)
Pruritus	1/13 (7.7%)		1/13 (7.7%)
Pruritus generalised	2/13 (15.4%)		0/13 (0%)
Rash maculo-papular	1/13 (7.7%)		1/13 (7.7%)
Blister	0/13 (0%)		1/13 (7.7%)
Dry skin	0/13 (0%)		1/13 (7.7%)
Palmar-plantar erythrodysaesthesia syndrome	1/13 (7.7%)		0/13 (0%)
Pigmentation disorder	0/13 (0%)		1/13 (7.7%)
Rash erythematous	0/13 (0%)		1/13 (7.7%)
Rash maculovesicular	0/13 (0%)		1/13 (7.7%)
Rash pruritic	0/13 (0%)		1/13 (7.7%)
Skin hyperpigmentation	0/13 (0%)		1/13 (7.7%)
Skin irritation	1/13 (7.7%)		0/13 (0%)
Skin lesion	1/13 (7.7%)		0/13 (0%)
Vascular disorders
Hypertension	0/13 (0%)		1/13 (7.7%)
Hypotension	0/13 (0%)		1/13 (7.7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.