Study of MLN8237 in Participants With Advanced Solid Tumors

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00962091

Collaborator

(none)

Enrollment

Location

Arms

57.2

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purposes of this study were to estimate the relative (Rel) bioavailability (BA) of an oral solution (OS) formulation of alisertib in reference to a powder-in-capsule (PIC) formulation, to characterize the effect of food on the single-dose pharmacokinetics (PK) of alisertib OS and enteric-coated tablets (ECT), to characterize the multiple-dose safety, tolerability, and steady-state PK of alisertib administered as an OS, and to characterize the multiple-dose safety and tolerability of alisertib administered as an ECT.

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

Detailed Description

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors. This study will look at the relative bioavailability (BA) (Part A), food effect and multiple-dose PK and safety of the oral solution (OS) (Part B) and food effect and safety of the enteric-coated tablet (ECT) formulation (Part C).

The study enrolled 53 patients (pts). Prior to initiation of Part A, 4 participants were enrolled in a dose escalation cohort. Participants in the study received:

• Alisertib 15 mg to 50 mg orally In the first 2 cycles of all 3 parts of the study, a single dose of alisertib was administered on Day 1 (PIC or OS in Part A [n=19 pts]; OS, in the fed or fasted state, in Part B [n=6 pts]; ECT, in the fed or fasted state, in Part C [n=24 pts]), In Part A, participants then continued on the PIC formulation at 40 mg BID for 7 days (Days 3

9). In Part B, participants continued on the OS formulation at a calculated dose administered BID for 7 days (Days 3 - 9). In Part C, the ECT formulation was continued at 40 mg BID for 7 days (Days 3 - 9); however, dose escalation to 50 mg BID was permitted after Cycle 1 based on tolerability and safety findings in the prior cycles. All participants took doses at a gap of 12 hours each day for 7 days followed by a 14-day rest period in a 21-days cycle for the remaining cycles.

This multi-center trial was conducted in the United States. The overall time to participate in this study was 30 months. Participants made multiple visits to the clinic, and final assessments were performed approximately 30 days after last dose of study drug.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Phase 1 Study of the Relative Bioavailability, Food Effect, Safety and Tolerability of MLN8237 in Patients With Advanced Solid Tumors

Actual Study Start Date :

Sep 25, 2009

Actual Primary Completion Date :

Dec 28, 2011

Actual Study Completion Date :

Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part A: Relative Bioavailability OS/PIC (Sequence A) A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part A: Relative Bioavailability PIC/OS (Sequence B) A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part B: OS Food Effect Fed/Fasted (Sequence A) Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part B: OS Food Effect Fasted/Fed (Sequence B) A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part C: ECT Food Effect Fed/Fasted (Sequence A) Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237
Experimental: Part C: ECT Food Effect Fasted/Fed (Sequence B) Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Drug: Alisertib Alisertib OS Alisertib PIC Alisertib PIC Other Names: MLN8237

Outcome Measures

Primary Outcome Measures

Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) [Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual adverse event (AE) that was judged by the investigator to be treatment related.]
Dose normalized Cmax was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) [Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Dose normalized AUClast was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food [Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Not performed.
Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food [Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Not performed.
Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration [Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Not performed.
Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration [Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Not performed.
Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration [Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Not performed.
Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food [Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Participants were randomized to receive 50-mg alisertib as an ECT (single, 50-mg strength tablets) under fasted or fed (following a standardized high-fat meal) conditions.
Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food [Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food [Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.]
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 30 days after the last dose of study drug (up to 27.4 months)]
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.
Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% [Up to 30 days after the last dose of study drug (up to 27.4 months)]
Laboratory AEs reported at an incidence of at least 5% overall in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, metabolism and nutrition disorders, investigations, and hepatobiliary disorders. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants With Abnormal Vital Signs Reported as Adverse Events [Up to 30 days after the last dose of study drug (up to 24 months approximately)]
Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study.

Secondary Outcome Measures

Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [At the completion of Cycle 2 and every 2 cycles (every 6 weeks) until Cycle 6 (18 weeks). After Cycle 6 (18 weeks), CT/MRI scans (with contrast) were to be performed every 3 cycles (9 weeks) until PD was documented.]
Best overall response is defined as the number of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum LD since the treatment started.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

18 years or older
Histologically or cytologically confirmed metastatic and/or advanced solid tumor
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
Voluntary written consent
Suitable venous access for study-required blood sampling
Measurable disease
Recovered from effects of prior antineoplastic therapy
Meet required entry laboratory and organ function levels

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

Female participants who are pregnant or lactating
Serious medical or psychiatric illness that could interfere with protocol completion
Major surgery within 14 days of first dose of alisertib
Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of alisertib
Nitrosoureas or mitomycin-C within 6 weeks before the first dose of alisertib.
Autologous stem cell transplant within 3 months before the first dose of alisertib, or prior allogeneic stem cell transplant at any time.
Active infection requiring systemic therapy, or other serious infection
Inability to swallow oral medication
Gastrointestinal (GI) disease or GI procedure that could interfere with oral absorption or tolerance of alisertib
Symptomatic brain metastasis
Uncontrolled cardiovascular condition
Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
Lactose-intolerant (Parts A and B only)
Prior history of metabolic acidosis (Parts A and B only)
Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of alisertib
A medical condition requiring use of pancreatic enzymes; or daily, chronic , or regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists.

Participants who intermittently use these medications must meet the following:

No use of PPI within 7 days of first dose of alisertib
No use of H2 antagonist or pancreatic enzymes within 24 hours of first dose of alisertib
Participants requiring full systemic anticoagulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology, A Medical Corporation	Santa Monica	California	United States	90404

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director: Medical Director Clinical Science, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00962091

Other Study ID Numbers:

C14010
U1111-1187-6657

First Posted:

Aug 19, 2009

Last Update Posted:

Mar 12, 2019

Last Verified:

Mar 1, 2019

Keywords provided by Millennium Pharmaceuticals, Inc.

Drug therapy

Additional relevant MeSH terms:

Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 3 investigative sites in the United States from 25 September 2009 to 01 July 2014.
Pre-assignment Detail	Participants with a diagnosis of advanced solid tumors were enrolled to receive alisertib in 1 of 4 parts: Dose Escalation, Part A (relative bioavailability), Part B (food effect and multiple-dose pharmacokinetics of alisertib oral solution [OS]), and Part C (food effect and safety of alisertib enteric-coated tablets [ECT]).

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability OS/PIC (Sequence A)	Part A: Relative Bioavailability PIC/OS (Sequence B)	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)	Part C: ECT Food Effect Fed/Fasted (Sequence A)	Part C: ECT Food Effect Fasted/Fed (Sequence B)
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Period Title: Overall Study
STARTED	4	9	10	3	3	12	12
COMPLETED	3	7	9	2	3	11	11
NOT COMPLETED	1	2	1	1	0	1	1

Baseline Characteristics

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability OS/PIC (Sequence A)	Part A: Relative Bioavailability PIC/OS (Sequence B)	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)	Part C: ECT Food Effect Fed/Fasted (Sequence A)	Part C: ECT Food Effect Fasted/Fed (Sequence B)	Total
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Total of all reporting groups
Overall Participants	4	9	10	3	3	12	12	53
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.3	54.6	54.0	51.7	57.7	57.4	55.2	55.5
Sex: Female, Male (Count of Participants)
Female	3 75%	2 22.2%	5 50%	1 33.3%	1 33.3%	7 58.3%	9 75%	28 52.8%
Male	1 25%	7 77.8%	5 50%	2 66.7%	2 66.7%	5 41.7%	3 25%	25 47.2%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	0 0%	0 0%	2 20%	0 0%	1 33.3%	2 16.7%	1 8.3%	6 11.3%
Not Hispanic or Latino	4 100%	9 100%	8 80%	3 100%	2 66.7%	10 83.3%	11 91.7%	47 88.7%
Race/Ethnicity, Customized (participants) [Number]
White	4 100%	8 88.9%	9 90%	3 100%	2 66.7%	12 100%	11 91.7%	49 92.5%
Black or African American	0 0%	0 0%	1 10%	0 0%	1 33.3%	0 0%	1 8.3%	3 5.7%
Asian	0 0%	1 11.1%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.9%
Region of Enrollment (participants) [Number]
United States	4 100%	9 100%	10 100%	3 100%	3 100%	12 100%	12 100%	53 100%
Height (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	167.7	172.6	172.8	160.3	169.1	169.2	160.5	167.4
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	72.7	85.5	81.4	66.3	77.7	73.0	66.1	74.7
Body Surface Area (BSA) (m^2) [Mean (Full Range) ]
Mean (Full Range) [m^2]	1.84	2.02	1.97	1.69	1.90	1.82	1.68	1.85

Outcome Measures

1. Primary Outcome

Title	Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Description	Dose normalized Cmax was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Time Frame	Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual adverse event (AE) that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK)-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.

Arm/Group Title	Part A: Alisertib OS	Part A: Alisertib PIC
Arm/Group Description	Alisertib 25 mg, OS, once on Day 1 in Cycle 1 or Cycle 2.	Alisertib 50 mg, PIC, orally once on Day 1 in Cycle 1 or Cycle 2.
Measure Participants	17	18
Mean (Standard Deviation) [nM/mg]	58.78 (22.583)	31.40 (11.404)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Alisertib OS, Part A: Alisertib PIC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 90% 1.52 to 2.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 Cmax values (difference=OS-PIC). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.

2. Primary Outcome

Title	Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Description	Dose normalized AUClast was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Time Frame	Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.

Arm/Group Title	Part A: Alisertib OS	Part A: Alisertib PIC
Arm/Group Description	Alisertib 25 mg, OS, once on Day 1 in Cycle 1 or Cycle 2.	Alisertib 50 mg, PIC, orally once on Day 1 in Cycle 1 or Cycle 2.
Measure Participants	17	17
Mean (Standard Deviation) [nM*hr/mg]	530.18 (177.750)	372.53 (145.190)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Alisertib OS, Part A: Alisertib PIC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 90% 1.08 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUClast values (difference=OS-PIC). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.

3. Primary Outcome

Title	Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Description	Not performed.
Time Frame	Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.

Arm/Group Title	Part B: Alisertib OS (Fed State)	Part B: Alisertib OS (Fasted State)
Arm/Group Description	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): Alisertib 35 mg oral solution (OS), in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle.	Alisertib 35 mg, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle.
Measure Participants	0	0

4. Primary Outcome

Title	Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Description	Not performed.
Time Frame	Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.

Arm/Group Title	Part B: Alisertib OS (Fed State)	Part B: Alisertib OS (Fasted State)
Arm/Group Description	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): Alisertib 35 mg oral solution (OS), in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle.	Alisertib 35 mg, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle.
Measure Participants	0	0

5. Primary Outcome

Title	Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration
Description	Not performed.
Time Frame	Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.

Arm/Group Title	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)
Arm/Group Description	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	0	0

6. Primary Outcome

Title	Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Description	Not performed.
Time Frame	Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.

Arm/Group Title	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)
Arm/Group Description	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	0	0

7. Primary Outcome

Title	Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Description	Not performed.
Time Frame	Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.

Arm/Group Title	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)
Arm/Group Description	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	0	0

8. Primary Outcome

Title	Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Description	Participants were randomized to receive 50-mg alisertib as an ECT (single, 50-mg strength tablets) under fasted or fed (following a standardized high-fat meal) conditions.
Time Frame	Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
PK-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.

Arm/Group Title	Part C: Alisertib ECT (Fasted State)	Part C: Alisertib ECT (Fed State)
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Measure Participants	14	14
Mean (Standard Deviation) [nM]	1757.9 (924.5)	1401.2 (501.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Alisertib OS, Part A: Alisertib PIC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 90% 0.66 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 Cmax values (difference=Fed-Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.

9. Primary Outcome

Title	Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Description
Time Frame	Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.

Arm/Group Title	Part C: Alisertib ECT (Fasted State)	Part C: Alisertib ECT (Fed State)
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Measure Participants	14	14
Mean (Standard Deviation) [nM*h]	23928.6 (14343.56)	24135.0 (11757.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Alisertib OS, Part A: Alisertib PIC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 90% 0.80 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUClast values (difference=Fed-Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.

10. Primary Outcome

Title	Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Description
Time Frame	Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.

Outcome Measure Data

Analysis Population Description
The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.

Arm/Group Title	Part C: Alisertib ECT (Fasted State)	Part C: Alisertib ECT (Fed State)
Arm/Group Description	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle.	Alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 or Cycle 2.
Measure Participants	11	14
Mean (Standard Error) [nM*h]	30627.3 (21000.29)	28507.1 (15637.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Alisertib OS, Part A: Alisertib PIC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 90% 0.68 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The CIs are calculated for the difference in the LS means of the ln-transformed Day 1 AUC values (difference=Fed-Fasted). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means.

11. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame	Up to 30 days after the last dose of study drug (up to 27.4 months)

Outcome Measure Data

Analysis Population Description
Safety population was defined as all participants who receive any amount of alisertib.

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability	Part B: OS Food Effect	Part C: ECT Food Effect
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	4	19	6	24
AE	4 100%	19 211.1%	6 60%	24 800%
SAE	2 50%	4 44.4%	2 20%	11 366.7%

12. Primary Outcome

Title	Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5%
Description	Laboratory AEs reported at an incidence of at least 5% overall in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, metabolism and nutrition disorders, investigations, and hepatobiliary disorders. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose of study drug (up to 27.4 months)

Outcome Measure Data

Analysis Population Description
Safety Population is defined as all participants who receive any amount of alisertib.

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability	Part B: OS Food Effect	Part C: ECT Food Effect
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	4	19	6	24
Neutropenia	3 75%	8 88.9%	2 20%	21 700%
Leukopenia	3 75%	7 77.8%	2 20%	17 566.7%
Anaemia	3 75%	4 44.4%	2 20%	15 500%
Thrombocytopenia	4 100%	3 33.3%	3 30%	10 333.3%
Lymphopenia	0 0%	3 33.3%	0 0%	3 100%
Hypomagnesaemia	0 0%	0 0%	1 10%	7 233.3%
Hyperglycaemia	0 0%	1 11.1%	1 10%	3 100%
Hypokalaemia	0 0%	0 0%	1 10%	3 100%
White blood cell count decreased	0 0%	0 0%	1 10%	5 166.7%
Aspartate aminotransferase increased	1 25%	0 0%	0 0%	6 200%
Gamma-glutamyltransferase increased	0 0%	1 11.1%	0 0%	2 66.7%
Lymphocyte count decreased	0 0%	0 0%	0 0%	3 100%
Neutrophil count decreased	0 0%	1 11.1%	0 0%	2 66.7%
Hyperbilirubinaemia	1 25%	0 0%	0 0%	3 100%

13. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as Adverse Events
Description	Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study.
Time Frame	Up to 30 days after the last dose of study drug (up to 24 months approximately)

Outcome Measure Data

Analysis Population Description
Safety Population is defined as all participants who receive any amount of alisertib.

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability	Part B: OS Food Effect	Part C: ECT Food Effect
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	4	19	6	24
Hypertension	1 25%	0 0%	1 10%	1 33.3%
Hypotension	0 0%	1 11.1%	1 10%	0 0%
Tachycardia	1 25%	1 11.1%	1 10%	0 0%
Sinus bradycardia	0 0%	0 0%	0 0%	1 33.3%

14. Secondary Outcome

Title	Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	Best overall response is defined as the number of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum LD since the treatment started.
Time Frame	At the completion of Cycle 2 and every 2 cycles (every 6 weeks) until Cycle 6 (18 weeks). After Cycle 6 (18 weeks), CT/MRI scans (with contrast) were to be performed every 3 cycles (9 weeks) until PD was documented.

Outcome Measure Data

Analysis Population Description
Efficacy analysis included all participants who had a baseline response assessment and at least one on-study response assessment.

Arm/Group Title	Dose Escalation Cohort	Part A: Relative Bioavailability OS/PIC (Sequence A)	Part A: Relative Bioavailability PIC/OS (Sequence B)	Part B: OS Food Effect Fed/Fasted (Sequence A)	Part B: OS Food Effect Fasted/Fed (Sequence B)	Part C: ECT Food Effect Fed/Fasted (Sequence A)	Part C: ECT Food Effect Fasted/Fed (Sequence B)
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
Measure Participants	2	8	9	3	3	12	12
Best Overall Response of CR or PR	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Best Overall Response of Stable Disease	0 0%	1 11.1%	5 50%	2 66.7%	1 33.3%	6 50%	6 50%

Adverse Events

	Dose Escalation Cohort		Part A: Relative Bioavailability		Part B: OS Food Effect		Part C: ECT Food Effect
Time Frame	Up to 30 days after the last dose of study drug (up to 27.4 months approximately)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Arm/Group Title	Dose Escalation Cohort		Part A: Relative Bioavailability		Part B: OS Food Effect		Part C: ECT Food Effect
Arm/Group Description	A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.		Alisertib 25 or 50 mg, OS, once on Day 1, in alternating dosage in Cycles 1 and 2, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycles 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.		Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose), OS, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1 and 2, in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.		Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, in alternating fed/fasted states in Cycles 1 and 2, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 and Cycle 2 in 23-day cycles, followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dose Escalation Cohort		Part A: Relative Bioavailability		Part B: OS Food Effect		Part C: ECT Food Effect
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		4/19 (21.1%)		2/6 (33.3%)		11/24 (45.8%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Neutropenia	1/4 (25%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Febrile neutropenia	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		2/24 (8.3%)
Gastrointestinal disorders
Vomiting	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Nausea	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Small intestinal obstruction	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
General disorders
Fatigue	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Pain	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Pyrexia	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Bile duct stone	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Infections and infestations
Sepsis	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Urinary tract infection	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Gastroenteritis viral	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Metabolism and nutrition disorders
Dehydration	1/4 (25%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Musculoskeletal pain	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Renal and urinary disorders
Anuria	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Hydronephrosis	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Renal failure acute	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Reproductive system and breast disorders
Female genital tract fistula	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Respiratory arrest	0/4 (0%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	Dose Escalation Cohort		Part A: Relative Bioavailability		Part B: OS Food Effect		Part C: ECT Food Effect
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		19/19 (100%)		6/6 (100%)		24/24 (100%)
Blood and lymphatic system disorders
Neutropenia	2/4 (50%)		8/19 (42.1%)		2/6 (33.3%)		17/24 (70.8%)
Leukopenia	3/4 (75%)		7/19 (36.8%)		2/6 (33.3%)		13/24 (54.2%)
Anaemia	3/4 (75%)		4/19 (21.1%)		2/6 (33.3%)		13/24 (54.2%)
Thrombocytopenia	4/4 (100%)		3/19 (15.8%)		3/6 (50%)		7/24 (29.2%)
Lymphopenia	0/4 (0%)		3/19 (15.8%)		0/6 (0%)		3/24 (12.5%)
Leukocytosis	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Cardiac disorders
Tachycardia	1/4 (25%)		1/19 (5.3%)		1/6 (16.7%)		1/24 (4.2%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Eye disorders
Vision blurred	1/4 (25%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Diplopia	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Eyelid pain	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Lacrimation increased	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Visual impairment	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Gastrointestinal disorders
Diarrhoea	0/4 (0%)		11/19 (57.9%)		1/6 (16.7%)		13/24 (54.2%)
Nausea	2/4 (50%)		10/19 (52.6%)		2/6 (33.3%)		9/24 (37.5%)
Stomatitis	4/4 (100%)		7/19 (36.8%)		5/6 (83.3%)		6/24 (25%)
Vomiting	0/4 (0%)		7/19 (36.8%)		1/6 (16.7%)		5/24 (20.8%)
Constipation	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		6/24 (25%)
Abdominal pain	1/4 (25%)		1/19 (5.3%)		1/6 (16.7%)		3/24 (12.5%)
Abdominal distension	1/4 (25%)		1/19 (5.3%)		0/6 (0%)		3/24 (12.5%)
Dysphagia	0/4 (0%)		2/19 (10.5%)		1/6 (16.7%)		1/24 (4.2%)
Abdominal pain upper	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		2/24 (8.3%)
Flatulence	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		1/24 (4.2%)
Abdominal discomfort	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		0/24 (0%)
Dry mouth	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)
Dyspepsia	1/4 (25%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Ascites	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Colitis	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Haematochezia	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Haemorrhoids	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Ileus	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
General disorders
Fatigue	3/4 (75%)		12/19 (63.2%)		4/6 (66.7%)		11/24 (45.8%)
Asthenia	1/4 (25%)		2/19 (10.5%)		1/6 (16.7%)		3/24 (12.5%)
Pyrexia	2/4 (50%)		2/19 (10.5%)		2/6 (33.3%)		1/24 (4.2%)
Oedema peripheral	1/4 (25%)		2/19 (10.5%)		0/6 (0%)		1/24 (4.2%)
Early satiety	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		1/24 (4.2%)
Chest discomfort	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Mucosal inflammation	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/4 (25%)		0/19 (0%)		0/6 (0%)		3/24 (12.5%)
Jaundice	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Immune system disorders
Drug hypersensitivity	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Infections and infestations
Oral candidiasis	1/4 (25%)		2/19 (10.5%)		2/6 (33.3%)		4/24 (16.7%)
Sinusitis	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		2/24 (8.3%)
Upper respiratory tract infection	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		1/24 (4.2%)
Urinary tract infection	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		2/24 (8.3%)
Nasopharyngitis	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Oral herpes	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Clostridium difficile infection	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Fungal skin infection	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Herpes simplex	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Skin infection	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Vaginal infection	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Injury, poisoning and procedural complications
Fall	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		1/24 (4.2%)
Contusion	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Forearm fracture	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Investigations
Weight decreased	0/4 (0%)		3/19 (15.8%)		0/6 (0%)		5/24 (20.8%)
White blood cell count decreased	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		5/24 (20.8%)
Aspartate aminotransferase increased	1/4 (25%)		0/19 (0%)		0/6 (0%)		4/24 (16.7%)
Gamma-glutamyltransferase increased	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		2/24 (8.3%)
Neutrophil count decreased	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		2/24 (8.3%)
Alanine aminotransferase increased	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Blood urea increased	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)
Lymphocyte count decreased	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)
Blood phosphorus decreased	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/4 (50%)		7/19 (36.8%)		1/6 (16.7%)		7/24 (29.2%)
Dehydration	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		4/24 (16.7%)
Hypomagnesaemia	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		5/24 (20.8%)
Hyperglycaemia	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		2/24 (8.3%)
Hypokalaemia	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		3/24 (12.5%)
Hypoalbuminaemia	1/4 (25%)		0/19 (0%)		0/6 (0%)		1/24 (4.2%)
Gout	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Hypercalcaemia	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Hyperuricaemia	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Hypophosphataemia	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Hyponatraemia	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/4 (25%)		6/19 (31.6%)		0/6 (0%)		4/24 (16.7%)
Myalgia	0/4 (0%)		4/19 (21.1%)		0/6 (0%)		0/24 (0%)
Pain in extremity	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		2/24 (8.3%)
Arthralgia	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Muscular weakness	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Musculoskeletal discomfort	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)
Musculoskeletal pain	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		0/24 (0%)
Axillary mass	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Flank pain	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Muscle spasms	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Musculoskeletal chest pain	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Pathological fracture	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Tumour flare	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Nervous system disorders
Headache	2/4 (50%)		2/19 (10.5%)		0/6 (0%)		4/24 (16.7%)
Somnolence	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		2/24 (8.3%)
Dizziness	1/4 (25%)		2/19 (10.5%)		0/6 (0%)		0/24 (0%)
Dysgeusia	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		1/24 (4.2%)
Cognitive disorder	2/4 (50%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Memory impairment	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		0/24 (0%)
Balance disorder	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Brain oedema	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Hypoaesthesia	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Nerve compression	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Psychiatric disorders
Depression	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		2/24 (8.3%)
Anxiety	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		1/24 (4.2%)
Confusional state	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		0/24 (0%)
Insomnia	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Delirium	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		2/24 (8.3%)
Vulvovaginal pruritus	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/4 (25%)		1/19 (5.3%)		0/6 (0%)		3/24 (12.5%)
Cough	0/4 (0%)		2/19 (10.5%)		1/6 (16.7%)		1/24 (4.2%)
Oropharyngeal pain	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		1/24 (4.2%)
Dyspnoea exertional	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		1/24 (4.2%)
Nasal congestion	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Paranasal sinus hypersecretion	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		0/24 (0%)
Pleural effusion	1/4 (25%)		0/19 (0%)		0/6 (0%)		0/24 (0%)
Productive cough	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/4 (25%)		5/19 (26.3%)		1/6 (16.7%)		13/24 (54.2%)
Palmar-plantar erythrodysaesthesia syndrome	0/4 (0%)		2/19 (10.5%)		1/6 (16.7%)		0/24 (0%)
Rash macular	0/4 (0%)		2/19 (10.5%)		0/6 (0%)		1/24 (4.2%)
Hyperhidrosis	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)
Palmar erythema	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		1/24 (4.2%)
Pruritus generalised	1/4 (25%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Rash	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		1/24 (4.2%)
Dry skin	0/4 (0%)		0/19 (0%)		1/6 (16.7%)		0/24 (0%)
Night sweats	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Papule	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Rash generalised	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Skin disorder	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Skin lesion	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Urticaria	0/4 (0%)		1/19 (5.3%)		0/6 (0%)		0/24 (0%)
Vascular disorders
Hypertension	1/4 (25%)		0/19 (0%)		1/6 (16.7%)		2/24 (8.3%)
Hypotension	0/4 (0%)		1/19 (5.3%)		1/6 (16.7%)		0/24 (0%)
Raynaud's phenomenon	0/4 (0%)		0/19 (0%)		0/6 (0%)		2/24 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

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.

Results Point of Contact

Name/Title	Medical Director
Organization	Takeda
Phone	+1-877-825-3327
Email	trialdisclosures@takeda.com

Responsible Party:

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00962091

Other Study ID Numbers:

C14010
U1111-1187-6657

First Posted:

Aug 19, 2009

Last Update Posted:

Mar 12, 2019

Last Verified:

Mar 1, 2019

Study of MLN8237 in Participants With Advanced Solid Tumors

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Participants who intermittently use these medications must meet the following:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact