A Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01094288
• Collaborator: (none)
• Enrollment: 41
• Locations: 4
• Arm: 1
• Actual Duration (Months): 76.6
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of alisertib in combination with docetaxel as a treatment for participants with advanced solid tumors, including castration-resistant prostate cancer, who were deemed by the investigator to be medically appropriate candidates for docetaxel therapy.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors; Adenocarcinoma of the Prostate	Drug: Alisertib; Drug: Docetaxel	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 including castration-resistant prostate cancer.

The study enrolled approximately 41 patients. Participants were enrolled to receive:

• Alisertib 10-40 mg + docetaxel 60-75 mg/m^2

All participants will receive alisertib (ECT) in dose escalating cohorts, orally, twice daily for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 [dose held for pharmacokinetic (PK) collection] along with docetaxel 75 mg/m^2, intravenous (IV) infusion on Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease (PD), unmanageable AEs or withdrawal of consent.

This multi-center trial is conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. Participants made multiple visits to the clinic, and were contacted every 12 weeks for up to 25.8 months after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen
• Actual Study Start Date: Aug 17, 2010
• Actual Primary Completion Date: Feb 28, 2014
• Actual Study Completion Date: Jan 4, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Alisertib + Docetaxel Alisertib in escalating dose (10-40 mg), enteric-coated tablets (ECT), orally, twice daily for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 along with docetaxel 60-75 mg/m^2, intravenous (IV) infusion on Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease (PD), unmanageable adverse events (AEs) or withdrawal of consent. The starting alisertib dose is 10 mg, orally, twice daily (total 20 mg/day).

Drug: Alisertib; Alisertib ECT; Other Names: MLN8237 ; Drug: Docetaxel; Docetaxel IV infusion

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)]

   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.

Secondary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for Docetaxel [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2]

2. AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2]

3. AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2]

4. Terminal Phase Elimination Half-life (T1/2) for Docetaxel [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2]

5. Cmax: Maximum Observed Plasma Concentration for Alisertib [Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1]

6. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib [Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1]

7. AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib [Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1]

8. Overall Response Rate (ORR) Assessed for Overall Participant Population [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

   ORR is defined as percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by response evaluation criteria in solid tumors (RECIST) v 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline. RECIST-Evaluable Population is subset of safety population who had measurable disease by RECIST v 1.1 at baseline and had at least 1 post baseline response. prostate specific antigen (PSA)-Evaluable Population is subset of the safety population who had a baseline PSA reference value (>5 ng/mL) and at least 12 weeks post-baseline PSA assessment for participants with no decline from baseline, or PSA progression within 12 weeks of treatment for participants with PSA decline from baseline.

9. Overall Response Rate for Prostate Cancer Participants [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

   ORR is defined as percentage of participants who achieved CR or PR as assessed by either RECIST v 1.1 or PSA response by prostate cancer working group 2 (PCWG2) criteria. According to RECIST v 1.1, CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PSA response by PCWG2 is defined as PSA at least 50% decrease in PSA value from baseline for 2 consecutive evaluations. PCWG2 defines PSA progression as the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.

10. Best Overall Response Rate Assessed by RECIST Criteria [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

    Best response rate is defined as the percentage of participants with CR, PR, CR+PR, stable disease (SD) and progressive disease (PD) as assessed by RECIST criteria 1.1 for target lesions and assessed by CT, PET or MRI. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

11. Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

    Best Response Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria PSA response is defined as at least 50% decrease in PSA value from baseline for 2 consecutive evaluations.

12. Duration of Response [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

    Duration of response is defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD), or censored at last SD or better.

13. Duration of Stable Disease (SD) [Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)]

    Duration of SD is defined as the time from first dose to first PD, or censored at last SD or better.

Eligibility Criteria

Criteria

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

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 advanced tumors and candidates for docetaxel treatment

• Measurable or evaluable disease is required. Participants must have clinical evidence of progressive disease or persistent disease

• Participants with castration-resistant prostate cancer (CRPC) are required to have

• Pathologically confirmed adenocarcinoma of the prostate

• Evidence of metastatic disease on bone scan or other imaging. Participants with prostate-specific antigen (PSA) elevation as the only manifestation of disease are not eligible.

• Progressive disease after at least 1 hormonal treatment with documented testosterone levels less than 50 ng/dl

• Concurrent use of an agent for testosterone suppression (e.g., luteinizing hormone-releasing hormone [LHRH] agonist) is required if the participants has not been surgically castrated

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Recovered to less than or equal to Grade 1 toxicity (CTCAE), to participant's baseline status (except alopecia) or deemed irreversible from the effects of prior cancer therapy and must have evidence of progressive or persistent disease

• Adequate bone marrow, liver and renal function

• Any use of opiates must be stable for at least 2 weeks prior to study entry

• 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

• Male participants who agree to practice effective barrier contraception during the entire study and through 6 months after the last dose of study drug OR agree to abstain from heterosexual intercourse

• Voluntary written consent

• Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

• Suitable venous access for blood sampling

Exclusion Criteria:

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

• Female participants who are lactating or pregnant

• Antineoplastic therapy or any experimental therapy within 21 days before the first dose of alisertib

• Prior or current investigational therapies within 4 weeks before the first dose of MLN8237

• Concurrent investigational treatment of treatment with any investigational products within 28 days before the first dose of alisertib

• Radiotherapy to greater than 40% of bone marrow or any radiotherapy (except localized, small field radiation) within 4 weeks prior to enrollment, unless reviewed and approved by the medical monitor

• 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 alisetib, or prior allogeneic stem cell transplant at any time.

• 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

• For CRPC participants:

• Radiotherapy or antiandrogen therapy for prostate cancer within 4 weeks prior to enrollment

• Prior treatment with antineoplastic chemotherapy or radioisotopes for advanced prostate cancer

• Use of products known to affect PSA levels within 4 weeks of enrollment

• Major surgery within 4 weeks of study enrollment

• Uncontrolled high blood pressure

• Participants with abnormal gastric or bowel function or who require continuous treatment with antacids or proton pump inhibitors

• Participants receiving chronic steroid therapy other than the following: low dose steroid for the control of nausea and vomiting, topical steroid, inhaled steroid or use of dexamethasone

• Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate 80

• Comorbid condition or unresolved toxicity that would preclude administration of docetaxel

• Prior history of Grade 2 or greater neurotoxicity or any toxicity that has not resolved to Grade 1 or below

• Symptomatic brain or other CNS metastasis

• 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

• Participants requiring full systemic anticoagulation

• Prior allogeneic bone marrow or other organ transplant

• Active infection requiring systemic therapy within 14 days preceding first dose, or other serious infection

• History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months

• Serious medical or psychiatric illness that could interfere with protocol completion

• Inability to swallow oral medication

• Prior treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens

• Prior treatment with more than 1 prior taxane-containing regimen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Indianapolis	Indiana	United States
2		Portland	Oregon	United States
3		San Antonio	Texas	United States
4		Seattle	Washington	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: NCT01094288
• Other Study ID Numbers: C14009
• First Posted: Mar 26, 2010
• Last Update Posted: Feb 15, 2019
• Last Verified: Oct 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma; Docetaxel

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 4 investigative sites in the United States from 17 August 2010 to 04 January 2017.
Pre-assignment Detail	Participants with a diagnosis of Advanced solid tumors, including castration-resistant prostate cancer were enrolled to receive alisertib Alisertib 10-40 mg + docetaxel 60-75 mg/m^2 intravenous (IV) infusion and granulocyte colony stimulating factor (GCSF) in escalating dose cohorts.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Period Title: Overall Study
STARTED	6	15	5	3	2	4	2	4
COMPLETED	4	5	1	1	2	4	2	2
NOT COMPLETED	2	10	4	2	0	0	0	2

Baseline Characteristics

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Total
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Total of all reporting groups
Overall Participants	6	15	5	3	2	4	2	4	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (5.20)	61.5 (13.10)	60.2 (16.75)	61.3 (8.62)	56.5 (2.12)	54.8 (18.73)	52.5 (26.16)	62.3 (25.71)	60.4 (14.07)
Sex: Female, Male (Count of Participants)
Female	0 0%	4 26.7%	1 20%	1 33.3%	1 50%	1 25%	2 100%	1 25%	11 26.8%
Male	6 100%	11 73.3%	4 80%	2 66.7%	1 50%	3 75%	0 0%	3 75%	30 73.2%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	0 0%	5 33.3%	0 0%	0 0%	0 0%	1 25%	1 50%	0 0%	7 17.1%
Not Hispanic or Latino	6 100%	10 66.7%	5 100%	3 100%	1 50%	3 75%	1 50%	4 100%	33 80.5%
Not Reported	0 0%	0 0%	0 0%	0 0%	1 50%	0 0%	0 0%	0 0%	1 2.4%
Race/Ethnicity, Customized (participants) [Number]
White	6 100%	15 100%	5 100%	2 66.7%	2 100%	3 75%	2 100%	3 75%	38 92.7%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	1 25%	2 4.9%
Other	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	1 2.4%
Region of Enrollment (participants) [Number]
United States	6 100%	15 100%	5 100%	3 100%	2 100%	4 100%	2 100%	4 100%	41 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	185.5 (11.02)	170.5 (10.04)	177.2 (12.13)	171.0 (10.08)	174.5 (0.71)	172.5 (10.98)	155.6 (8.08)	174.9 (6.99)	173.6 (11.32)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	100.25 (15.842)	82.73 (16.963)	94.15 (25.623)	87.73 (31.987)	76.90 (8.344)	85.97 (15.987)	62.05 (11.950)	87.05 (21.025)	86.50 (19.550)
Body Surface Area (BSA) (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	2.269 (0.2329)	1.973 (0.2533)	2.138 (0.3541)	2.025 (0.4316)	1.929 (0.1009)	2.026 (0.2420)	1.635 (0.2005)	2.046 (0.2945)	2.034 (0.2878)

Outcome Measures

1. Primary 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 enrollment through 30 days after the last dose of study drug (approximately up to 77 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least 1 dose of any study drug.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	15	5	3	2	4	2	4
AEs	6 100%	15 100%	5 100%	3 100%	2 100%	4 100%	2 100%	4 100%
SAEs	3 50%	8 53.3%	3 60%	2 66.7%	1 50%	3 75%	2 100%	2 50%

2. Secondary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Docetaxel
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter population was defined as all participants who had sufficient dosing data and plasma alisertib or docetaxel concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	15	5	3	2	4	2	4
Cycle 1 Day 1	2392.7 (60.2)	1730.4 (26.5)	1587.0 (34.1)	1717.6 (51.9)	3751.4 (80.8)	1159.9 (13.8)	2232.9 (19.8)	1386.6 (47.0)
Cycle 2 Day 1	1825.1 (25.9)	1957.0 (23.4)	2146.6 (19.4)	3299.9 (0.9)	1649.7 (19.1)	1061.6 (24.8)	2504.6 (28.0)	1627.8 (17.2)

3. Secondary Outcome

Title	AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib or docetaxel concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	15	5	3	2	4	2	4
Cycle 1 Day 1	2328.3 (69.5)	1925.7 (21.4)	1750.1 (23.1)	2163.4 (52.8)	1830.0 (NA)	1593.1 (14.0)	2394.6 (2.7)	1579.8 (45.4)
Cycle 2 Day 1	1750.8 (23.1)	2416.4 (23.7)	25.5 (2174.6)	7811.5 (87.5)	1622.8 (35.0)	1596.0 (19.9)	2895.7 (16.3)	2510.0 (NA)

4. Secondary Outcome

Title	AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib or docetaxel concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	15	5	3	2	4	2	4
Cycle 1 Day 1	2653.3 (68.1)	2240.6 (23.9)	2007.3 (15.7)	3570.0 (NA)	2130.0 (NA)	1734.7 (9.6)	2600.0 (0.0)	1730.9 (53.9)
Cycle 2 Day 1	1918.0 (21.4)	2632.2 (28.0)	2019.8 (10.1)	4000.0 (NA)	1785.4 (35.6)	1631.0 (9.9)	3099.0 (14.3)	3120.0 (NA)

5. Secondary Outcome

Title	Terminal Phase Elimination Half-life (T1/2) for Docetaxel
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib or docetaxel concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	15	5	3	2	4	2	4
Cycle 1 Day 1	21.80 (4.339)	22.88 (4.733)	24.00 (6.934)	15.60 (NA)	30.70 (NA)	16.34 (5.684)	19.25 (2.051)	24.80 (6.444)
Cycle 2 Day 1	24.18 (2.050)	20.73 (5.845)	20.40 (2.121)	16.40 (NA)	25.10 (2.546)	22.00 (2.404)	16.95 (0.636)	26.00 (NA)

6. Secondary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Alisertib
Time Frame	Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg	Alisertib 20 mg	Alisertib 30 mg	Alisertib 40 mg
Arm/Group Description	Alisertib 10 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 of each cycle (21-day cycle).	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.	Alisertib 40 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.
Measure Participants	6	15	16	4
Cycle 1 Day 1	290.4 (22.1)	557.5 (57.3)	751.6 (31.3)	1346.4 (49.8)
Cycle 1 Day 5/Day 7	435.8 (31.0)	1140.6 (44.7)	1637.9 (52.1)	1766.3 (40.1)

7. Secondary Outcome

Title	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib
Time Frame	Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg	Alisertib 20 mg	Alisertib 30 mg	Alisertib 40 mg
Arm/Group Description	Alisertib 10 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 of each cycle (21-day cycle).	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.	Alisertib 40 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.
Measure Participants	6	15	26	4
Cycle 1 Day 1	2.050	4.000	3.560	1.500
Cycle 1 Day 5/Day 7	3.510	3.030	2.030	1.975

8. Secondary Outcome

Title	AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib
Time Frame	Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

Outcome Measure Data

Analysis Population Description

PK parameter population was defined as all participants who had sufficient dosing data and plasma alisertib concentration-time data to permit the calculation of any PK parameter. Here number analyzed is the number of participants with data available for analysis at the given time point.

Arm/Group Title	Alisertib 10 mg	Alisertib 20 mg	Alisertib 30 mg	Alisertib 40 mg
Arm/Group Description	Alisertib 10 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 of each cycle (21-day cycle).	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.	Alisertib 40 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2. Assessment was performed on Day 5 if alisertib was given on a 5 day schedule.
Measure Participants	6	15	16	4
Cycle 1 Day 1	1635.0 (28.3)	3303.0 (46.1)	4387.5 (30.1)	8013.7 (43.1)
Cycle 1 Day 5/Day 7	3052.8 (42.0)	8546.0 (49.7)	13199.1 (60.8)	12630.0 (27.7)

9. Secondary Outcome

Title	Overall Response Rate (ORR) Assessed for Overall Participant Population
Description	ORR is defined as percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by response evaluation criteria in solid tumors (RECIST) v 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline. RECIST-Evaluable Population is subset of safety population who had measurable disease by RECIST v 1.1 at baseline and had at least 1 post baseline response. prostate specific antigen (PSA)-Evaluable Population is subset of the safety population who had a baseline PSA reference value (>5 ng/mL) and at least 12 weeks post-baseline PSA assessment for participants with no decline from baseline, or PSA progression within 12 weeks of treatment for participants with PSA decline from baseline.
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

Response-Evaluable Population included participants who were either RECIST evaluable and/or PSA-evaluable.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	10	1	2	2	4	1	2
Number (95% Confidence Interval) [percentage of participants]	50 833.3%	10 66.7%	100 2000%	50 1666.7%	0 0%	25 625%	0 0%	50 1250%

10. Secondary Outcome

Title	Overall Response Rate for Prostate Cancer Participants
Description	ORR is defined as percentage of participants who achieved CR or PR as assessed by either RECIST v 1.1 or PSA response by prostate cancer working group 2 (PCWG2) criteria. According to RECIST v 1.1, CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PSA response by PCWG2 is defined as PSA at least 50% decrease in PSA value from baseline for 2 consecutive evaluations. PCWG2 defines PSA progression as the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

Response-Evaluable Population included participants who were either RECIST evaluable or PSA-evaluable. Here, number of participants analyzed are the enrolled participants who had castration-resistant prostate cancer (CRPC) and were evaluable by either RECIST or PSA response criteria.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	5	0	1	0	1	0	1
Number (95% Confidence Interval) [percentage of participants]	50 833.3%	20 133.3%	100 2000%	0 0%	100 5000%

11. Secondary Outcome

Title	Best Overall Response Rate Assessed by RECIST Criteria
Description	Best response rate is defined as the percentage of participants with CR, PR, CR+PR, stable disease (SD) and progressive disease (PD) as assessed by RECIST criteria 1.1 for target lesions and assessed by CT, PET or MRI. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

RECIST-Evaluable Population included a subset of the safety population who had measurable disease by RECIST v 1.1 at baseline and had at least 1 post baseline response assessment.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	9	1	2	2	4	1	2
Complete Response (CR)	0 0%	0 0%	100 2000%	0 0%	0 0%	0 0%	0 0%	0 0%
Partial Response (PR)	50 833.3%	11 73.3%	0 0%	50 1666.7%	0 0%	25 625%	0 0%	50 1250%
CR+PR	50 833.3%	11 73.3%	100 2000%	50 1666.7%	0 0%	25 625%	0 0%	50 1250%
Stable Disease (SD)	50 833.3%	67 446.7%	0 0%	0 0%	50 2500%	0 0%	0 0%	50 1250%
Progressive Disease (PD)	0 0%	22 146.7%	0 0%	50 1666.7%	50 2500%	75 1875%	100 5000%	0 0%

12. Secondary Outcome

Title	Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria
Description	Best Response Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria PSA response is defined as at least 50% decrease in PSA value from baseline for 2 consecutive evaluations.
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

PSA-Evaluable Population is a subset of the safety population who had a baseline PSA reference value (>5 ng/mL) and at least 12 weeks post-baseline PSA assessment for participants with no decline from baseline, or PSA progression within 12 weeks of treatment for participants with PSA decline from baseline.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	6	5	0	1	0	0	0	0
≥50% Reduction from Baseline	67 1116.7%	80 533.3%	100 2000%
<50% Reduction from Baseline	33 550%	20 133.3%	0 0%

13. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD), or censored at last SD or better.
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

Response-Evaluable population includes patients that are either RECIST-evaluable or PSA-evaluable. Here, number of participants analyzed are the participants who were responders. A responder that did not experience disease progression were censored at the last response assessment that is SD or better.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	3	1	1	1	0	1	0	1
Median (Full Range) [days]	187	342	830	176	79	NA

14. Secondary Outcome

Title	Duration of Stable Disease (SD)
Description	Duration of SD is defined as the time from first dose to first PD, or censored at last SD or better.
Time Frame	Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)

Outcome Measure Data

Analysis Population Description

Response-Evaluable population includes patients that are either RECIST-evaluable or PSA-evaluable. Here, number of participants analyzed are the participants who had SD. For a participants that has not progressed, duration of SD is censored at the last response assessment that is SD or better.

Arm/Group Title	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2	Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2	Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF	Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.	Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.	Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
Measure Participants	3	6	0	0	1	0	0	1
Median (Full Range) [days]	253	NA	309	134

Adverse Events

Time Frame	From signing of the informed consent form up to 30 days after the last dose of study drug (up to 25.8 months)
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	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF		Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
Arm/Group Description	Alisertib 10 mg, enteric-coated tablets (ECT), orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 28 cycles, or until the occurrence of PD, unmanageable adverse events (AEs) or withdrawal of consent.		Alisertib 20 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 34 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 36 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 17 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 30 mg, ECT, orally, twice daily for 7 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 15 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 60 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 30 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 2 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.		Alisertib 40 mg, ECT, orally, twice daily for 5 days in Cycle 1, 3 and onwards; and orally twice daily from Day 3 to Day 7 in Cycle 2 followed by 14 day rest period along with docetaxel 75 mg/m^2, intravenous infusion on Day 1 of each cycle (21-day cycle) and granulocyte colony stimulating factor (GCSF) as per standard of care for a maximum of 5 cycles, or until the occurrence of PD, unmanageable AEs or withdrawal of consent.
All Cause Mortality
	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF		Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF		Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		10/15 (66.7%)		3/5 (60%)		2/3 (66.7%)		1/2 (50%)		3/4 (75%)		2/2 (100%)		2/4 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	1/6 (16.7%)		6/15 (40%)		1/5 (20%)		1/3 (33.3%)		1/2 (50%)		1/4 (25%)		0/2 (0%)		1/4 (25%)
Neutropenia	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Anaemia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Gastrointestinal disorders
Stomatitis	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Diarrhoea	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Constipation	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Infections and infestations
Urinary tract infection	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Clostridium difficile colitis	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		1/2 (50%)		0/4 (0%)
Pneumonia	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Wound infection	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Pseudomonas infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Dehydration	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		1/2 (50%)		0/4 (0%)
Hypokalaemia	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Flank pain	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Metastatic carcinoma of the bladder	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Colorectal cancer	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Metastases to central nervous system	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Cancer pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Nervous system disorders
Cerebellar infarction	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Headache	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Psychiatric disorders
Confusional state	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Renal and urinary disorders
Acute kidney injury	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hydronephrosis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haematuria	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2		Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2		Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF		Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		14/15 (93.3%)		5/5 (100%)		3/3 (100%)		2/2 (100%)		4/4 (100%)		2/2 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Neutropenia	6/6 (100%)		9/15 (60%)		5/5 (100%)		3/3 (100%)		2/2 (100%)		4/4 (100%)		2/2 (100%)		2/4 (50%)
Anaemia	2/6 (33.3%)		6/15 (40%)		3/5 (60%)		3/3 (100%)		1/2 (50%)		3/4 (75%)		1/2 (50%)		1/4 (25%)
Leukopenia	1/6 (16.7%)		4/15 (26.7%)		2/5 (40%)		1/3 (33.3%)		1/2 (50%)		2/4 (50%)		2/2 (100%)		1/4 (25%)
Thrombocytopenia	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Granulocytopenia	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Lymphopenia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Febrile neutropenia	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Lymphadenopathy	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Ear and labyrinth disorders
Deafness unilateral	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Tinnitus	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Eye disorders
Lacrimation increased	0/6 (0%)		4/15 (26.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dry eye	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Blepharospasm	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Dacryostenosis acquired	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Glaucoma	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Vision blurred	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Gastrointestinal disorders
Diarrhoea	4/6 (66.7%)		9/15 (60%)		1/5 (20%)		0/3 (0%)		1/2 (50%)		1/4 (25%)		1/2 (50%)		3/4 (75%)
Stomatitis	1/6 (16.7%)		9/15 (60%)		2/5 (40%)		1/3 (33.3%)		0/2 (0%)		1/4 (25%)		1/2 (50%)		4/4 (100%)
Constipation	2/6 (33.3%)		4/15 (26.7%)		4/5 (80%)		2/3 (66.7%)		0/2 (0%)		3/4 (75%)		0/2 (0%)		1/4 (25%)
Vomiting	0/6 (0%)		7/15 (46.7%)		2/5 (40%)		0/3 (0%)		1/2 (50%)		2/4 (50%)		0/2 (0%)		2/4 (50%)
Nausea	0/6 (0%)		7/15 (46.7%)		3/5 (60%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Abdominal pain	1/6 (16.7%)		3/15 (20%)		2/5 (40%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		1/4 (25%)
Dyspepsia	0/6 (0%)		2/15 (13.3%)		3/5 (60%)		0/3 (0%)		1/2 (50%)		1/4 (25%)		0/2 (0%)		1/4 (25%)
Abdominal pain upper	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Dry mouth	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Dysphagia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Oral pain	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Haemorrhoids	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Oral discomfort	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Rectal discharge	0/6 (0%)		0/15 (0%)		1/5 (20%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Abdominal discomfort	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Abdominal distension	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dental caries	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Flatulence	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Gastrointestinal inflammation	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haematochezia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Intestinal mass	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Oral mucosal erythema	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Proctalgia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rectal haemorrhage	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Swollen tongue	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
General disorders
Fatigue	3/6 (50%)		10/15 (66.7%)		4/5 (80%)		1/3 (33.3%)		2/2 (100%)		1/4 (25%)		2/2 (100%)		2/4 (50%)
Oedema peripheral	3/6 (50%)		3/15 (20%)		1/5 (20%)		1/3 (33.3%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		1/4 (25%)
Pyrexia	1/6 (16.7%)		1/15 (6.7%)		1/5 (20%)		1/3 (33.3%)		1/2 (50%)		0/4 (0%)		1/2 (50%)		1/4 (25%)
Non-cardiac chest pain	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Asthenia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Catheter site erythema	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Catheter site haematoma	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Chest discomfort	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Face oedema	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Influenza like illness	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Thrombosis in device	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hepatobiliary disorders
Cholecystitis chronic	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Immune system disorders
Seasonal allergy	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Infections and infestations
Oral candidiasis	1/6 (16.7%)		2/15 (13.3%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		2/4 (50%)		1/2 (50%)		0/4 (0%)
Upper respiratory tract infection	3/6 (50%)		3/15 (20%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Fungal skin infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Herpes zoster	2/6 (33.3%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pneumonia	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Staphylococcal skin infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Urinary tract infection	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Bacteraemia	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Bronchitis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Cellulitis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Clostridium difficile colitis	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Clostridium difficile infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Conjunctivitis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dermatophytosis	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Device related infection	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Fungal infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Genital infection fungal	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Herpes simplex	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Localised infection	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Lower respiratory tract infection	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Onychomycosis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pharyngitis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Phlebitis infective	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rash pustular	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Subcutaneous abscess	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Tooth abscess	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Tooth infection	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Vaginal infection	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Viral upper respiratory tract infection	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Vulvovaginal candidiasis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Vulvovaginal mycotic infection	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Stoma site pain	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Skin wound	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Post procedural haematuria	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Laceration	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Incision site pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Arthropod bite	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Skin abrasion	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Post-traumatic pain	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Infusion related reaction	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Fall	1/6 (16.7%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Investigations
Weight decreased	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Weight increased	2/6 (33.3%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Alanine aminotransferase increased	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Aspartate aminotransferase increased	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Blood bilirubin increased	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Blood creatinine increased	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Electrocardiogram QT prolonged	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Urine cytology abnormal	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/6 (0%)		4/15 (26.7%)		4/5 (80%)		2/3 (66.7%)		1/2 (50%)		1/4 (25%)		1/2 (50%)		3/4 (75%)
Dehydration	0/6 (0%)		5/15 (33.3%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		2/2 (100%)		1/4 (25%)
Hypokalaemia	0/6 (0%)		5/15 (33.3%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Hypophosphataemia	0/6 (0%)		3/15 (20%)		2/5 (40%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hypomagnesaemia	0/6 (0%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Hyponatraemia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		1/2 (50%)		0/4 (0%)
Hyperglycaemia	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hypoalbuminaemia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Hypocalcaemia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hypovolaemia	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Fluid overload	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hyperkalaemia	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)		4/15 (26.7%)		1/5 (20%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Back pain	2/6 (33.3%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		2/4 (50%)
Bone pain	1/6 (16.7%)		3/15 (20%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Muscle spasms	1/6 (16.7%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Myalgia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Muscular weakness	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Musculoskeletal chest pain	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Pain in extremity	2/6 (33.3%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Arthritis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Coccydynia	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Flank pain	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Joint stiffness	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Joint swelling	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Musculoskeletal stiffness	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Neck pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Nervous system disorders
Dysgeusia	4/6 (66.7%)		5/15 (33.3%)		3/5 (60%)		1/3 (33.3%)		2/2 (100%)		0/4 (0%)		0/2 (0%)		2/4 (50%)
Neuropathy peripheral	4/6 (66.7%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		1/2 (50%)		1/4 (25%)		0/2 (0%)		1/4 (25%)
Peripheral sensory neuropathy	3/6 (50%)		5/15 (33.3%)		0/5 (0%)		0/3 (0%)		2/2 (100%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dizziness	3/6 (50%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		1/2 (50%)		0/4 (0%)
Headache	1/6 (16.7%)		5/15 (33.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Presyncope	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Lethargy	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Myoclonus	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Peripheral motor neuropathy	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Sinus headache	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Somnolence	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Product Issues
Device occlusion	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Psychiatric disorders
Anxiety	2/6 (33.3%)		0/15 (0%)		1/5 (20%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Insomnia	1/6 (16.7%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Depression	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		1/2 (50%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Agitation	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Renal and urinary disorders
Haematuria	1/6 (16.7%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Urinary incontinence	1/6 (16.7%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Urinary retention	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Bladder pain	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Bladder spasm	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haemorrhage urinary tract	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hydronephrosis	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		0/4 (0%)
Oliguria	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pollakiuria	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Renal failure	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/6 (16.7%)		4/15 (26.7%)		1/5 (20%)		2/3 (66.7%)		0/2 (0%)		0/4 (0%)		1/2 (50%)		1/4 (25%)
Cough	2/6 (33.3%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		2/2 (100%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Epistaxis	2/6 (33.3%)		2/15 (13.3%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Oropharyngeal pain	1/6 (16.7%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Atelectasis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haemoptysis	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rhinorrhoea	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Sinus congestion	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Asthma	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dysphonia	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haemothorax	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hypoxia	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Laryngeal oedema	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Nasal congestion	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Paranasal sinus hypersecretion	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pharyngeal inflammation	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pleural effusion	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pleuritic pain	0/6 (0%)		0/15 (0%)		0/5 (0%)		1/3 (33.3%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rhinalgia	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rhinitis allergic	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Tachypnoea	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Throat irritation	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Upper-airway cough syndrome	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Alopecia	3/6 (50%)		7/15 (46.7%)		3/5 (60%)		1/3 (33.3%)		2/2 (100%)		1/4 (25%)		1/2 (50%)		2/4 (50%)
Rash	3/6 (50%)		3/15 (20%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Nail disorder	0/6 (0%)		3/15 (20%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rash papular	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Onycholysis	3/6 (50%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		1/2 (50%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rash macular	1/6 (16.7%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Rash pruritic	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		2/2 (100%)		0/4 (0%)
Nail discolouration	1/6 (16.7%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pruritus	0/6 (0%)		1/15 (6.7%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Dermatitis contact	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Night sweats	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Palmar-plantar erythrodysaesthesia syndrome	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Rash maculo-papular	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Skin exfoliation	0/6 (0%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Cold sweat	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dermal cyst	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		1/4 (25%)		0/2 (0%)		0/4 (0%)
Dermatitis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dermatitis allergic	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Dry skin	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Ecchymosis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Eczema	0/6 (0%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		1/4 (25%)
Exfoliative rash	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hyperhidrosis	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Intertrigo	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Onychalgia	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Petechiae	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pruritus generalised	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Vascular disorders
Hypotension	0/6 (0%)		3/15 (20%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		2/2 (100%)		0/4 (0%)
Hypertension	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Lymphoedema	1/6 (16.7%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Embolism	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Haematoma	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Hot flush	0/6 (0%)		0/15 (0%)		1/5 (20%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Orthostatic hypotension	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Pallor	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Phlebitis	0/6 (0%)		1/15 (6.7%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Thrombophlebitis superficial	1/6 (16.7%)		0/15 (0%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)
Flushing	1/6 (16.7%)		2/15 (13.3%)		0/5 (0%)		0/3 (0%)		0/2 (0%)		0/4 (0%)		0/2 (0%)		0/4 (0%)

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.