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

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ClinicalTrials.gov Identifier: NCT01094288
Recruitment Status : Completed
First Posted : March 26, 2010
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Adenocarcinoma of the Prostate
Interventions Drug: Alisertib
Drug: Docetaxel
Enrollment 41
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 Details 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
Hide 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 [1] 5 1 1 2 4 2 2
Not Completed 2 10 4 2 0 0 0 2
Reason Not Completed
Adverse Event             0             3             1             1             0             0             0             0
Withdrawal by Subject             0             1             2             0             0             0             0             2
Initiation of Alternative Therapy             0             0             1             0             0             0             0             0
Reason not Specified             2             3             0             1             0             0             0             0
Ongoing Participants             0             3             0             0             0             0             0             0
[1]
Completed=Completed 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 Total
Hide 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 Number of Baseline Participants 6 15 5 3 2 4 2 4 41
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least 1 dose of any study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
Female
0
   0.0%
4
  26.7%
1
  20.0%
1
  33.3%
1
  50.0%
1
  25.0%
2
 100.0%
1
  25.0%
11
  26.8%
Male
6
 100.0%
11
  73.3%
4
  80.0%
2
  66.7%
1
  50.0%
3
  75.0%
0
   0.0%
3
  75.0%
30
  73.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
Hispanic or Latino 0 5 0 0 0 1 1 0 7
Not Hispanic or Latino 6 10 5 3 1 3 1 4 33
Not Reported 0 0 0 0 1 0 0 0 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
White 6 15 5 2 2 3 2 3 38
Black or African American 0 0 0 0 0 1 0 1 2
Other 0 0 0 1 0 0 0 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
6 15 5 3 2 4 2 4 41
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
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  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
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)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 6 participants 15 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants 41 participants
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)
[1]
Measure Description: BSA (m^2) = square root [height (cm) * weight (kg)/3600].
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 5 3 2 4 2 4
Measure Type: Number
Unit of Measure: participants
AEs 6 15 5 3 2 4 2 4
SAEs 3 8 3 2 1 3 2 2
2.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Docetaxel
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 5 3 2 4 2 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 1 Number Analyzed 6 participants 13 participants 5 participants 3 participants 2 participants 4 participants 2 participants 4 participants
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 Number Analyzed 6 participants 9 participants 4 participants 2 participants 2 participants 4 participants 2 participants 2 participants
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
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 5 3 2 4 2 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
Cycle 1 Day 1 Number Analyzed 6 participants 13 participants 4 participants 3 participants 1 participants 3 participants 2 participants 4 participants
2328.3
(69.5%)
1925.7
(21.4%)
1750.1
(23.1%)
2163.4
(52.8%)
1830.0 [1] 
(NA%)
1593.1
(14.0%)
2394.6
(2.7%)
1579.8
(45.4%)
Cycle 2 Day 1 Number Analyzed 5 participants 9 participants 3 participants 2 participants 2 participants 3 participants 2 participants 1 participants
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 [1] 
(NA%)
[1]
Geometric coefficient of variation is not estimable as only 1 participants is assessed.
4.Secondary Outcome
Title AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 5 3 2 4 2 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
Cycle 1 Day 1 Number Analyzed 5 participants 9 participants 4 participants 1 participants 1 participants 3 participants 2 participants 3 participants
2653.3
(68.1%)
2240.6
(23.9%)
2007.3
(15.7%)
3570.0 [1] 
(NA%)
2130.0 [1] 
(NA%)
1734.7
(9.6%)
2600.0
(0.0%)
1730.9
(53.9%)
Cycle 2 Day 1 Number Analyzed 5 participants 8 participants 2 participants 1 participants 2 participants 2 participants 2 participants 1 participants
1918.0
(21.4%)
2632.2
(28.0%)
2019.8
(10.1%)
4000.0 [1] 
(NA%)
1785.4
(35.6%)
1631.0
(9.9%)
3099.0
(14.3%)
3120.0 [1] 
(NA%)
[1]
Geometric Coefficient of Variation is not estimable as only 1 participants is assessed.
5.Secondary Outcome
Title Terminal Phase Elimination Half-life (T1/2) for Docetaxel
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 5 3 2 4 2 4
Mean (Standard Deviation)
Unit of Measure: hr
Cycle 1 Day 1 Number Analyzed 5 participants 9 participants 4 participants 1 participants 1 participants 3 participants 2 participants 3 participants
21.80  (4.339) 22.88  (4.733) 24.00  (6.934) 15.60 [1]   (NA) 30.70 [1]   (NA) 16.34  (5.684) 19.25  (2.051) 24.80  (6.444)
Cycle 2 Day 1 Number Analyzed 5 participants 8 participants 2 participants 1 participants 2 participants 2 participants 2 participants 1 participants
24.18  (2.050) 20.73  (5.845) 20.40  (2.121) 16.40 [1]   (NA) 25.10  (2.546) 22.00  (2.404) 16.95  (0.636) 26.00 [1]   (NA)
[1]
Standard deviation is not estimable as only 1 participants is assessed.
6.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Alisertib
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
Cycle 1 Day 1 Number Analyzed 5 participants 15 participants 16 participants 4 participants
290.4
(22.1%)
557.5
(57.3%)
751.6
(31.3%)
1346.4
(49.8%)
Cycle 1 Day 5/Day 7 Number Analyzed 6 participants 13 participants 11 participants 4 participants
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
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 26 4
Median (Full Range)
Unit of Measure: hr
Cycle 1 Day 1 Number Analyzed 5 participants 15 participants 16 participants 4 participants
2.050
(2.00 to 3.00)
4.000
(2.00 to 9.98)
3.560
(2.00 to 12.00)
1.500
(1.00 to 7.58)
Cycle 1 Day 5/Day 7 Number Analyzed 6 participants 13 participants 11 participants 4 participants
3.510
(1.87 to 8.22)
3.030
(2.00 to 9.40)
2.030
(2.00 to 8.00)
1.975
(1.08 to 3.00)
8.Secondary Outcome
Title AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 15 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*nmol/L
Cycle 1 Day 1 Number Analyzed 5 participants 15 participants 16 participants 4 participants
1635.0
(28.3%)
3303.0
(46.1%)
4387.5
(30.1%)
8013.7
(43.1%)
Cycle 1 Day 5/Day 7 Number Analyzed 6 participants 13 participants 11 participants 4 participants
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 10 1 2 2 4 1 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(12 to 88)
10
(0 to 45)
100 [1] 
(NA to NA)
50
(1 to 99)
0
(0 to 0)
25
(1 to 81)
0
(0 to 0)
50
(1 to 99)
[1]
95% Confidence Interval is not estimable as only 1 participants is assessed.
10.Secondary Outcome
Title Overall Response Rate for Prostate Cancer Participants
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 5 0 1 0 1 0 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(12 to 88)
20
(1 to 72)
100 [1] 
(NA to NA)
0
(0 to 0)
100 [1] 
(NA to NA)
[1]
95% Confidence Interval is not estimable as only 1 participants is assessed.
11.Secondary Outcome
Title Best Overall Response Rate Assessed by RECIST Criteria
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 9 1 2 2 4 1 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Complete Response (CR)
0
(0 to 0)
0
(0 to 0)
100 [1] 
(NA to NA)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
Partial Response (PR)
50
(12 to 88)
11
(0 to 48)
0
(0 to 0)
50
(1 to 99)
0
(0 to 0)
25
(1 to 81)
0
(0 to 0)
50
(1 to 99)
CR+PR
50
(12 to 88)
11
(0 to 48)
100 [1] 
(NA to NA)
50
(1 to 99)
0
(0 to 0)
25
(1 to 81)
0
(0 to 0)
50
(1 to 99)
Stable Disease (SD)
50
(12 to 88)
67
(30 to 93)
0
(0 to 0)
0
(0 to 0)
50
(1 to 99)
0
(0 to 0)
0
(0 to 0)
50
(1 to 99)
Progressive Disease (PD)
0
(0 to 0)
22
(3 to 60)
0
(0 to 0)
50
(1 to 99)
50
(1 to 99)
75
(19 to 99)
100 [1] 
(NA to NA)
0
(0 to 0)
[1]
95% Confidence Interval is not estimable as only 1 participants is assessed.
12.Secondary Outcome
Title Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 5 0 1 0 0 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
≥50% Reduction from Baseline
67
(22 to 96)
80
(28 to 99)
100 [1] 
(NA to NA)
<50% Reduction from Baseline
33
(4 to 78)
20
(1 to 72)
0
(0 to 0)
[1]
95% Confidence Interval is not estimable as only 1 participants is assessed.
13.Secondary Outcome
Title Duration of Response
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 1 1 1 0 1 0 1
Median (Full Range)
Unit of Measure: days
187
(43 to 187)
342
(342 to 342)
830
(830 to 830)
176
(176 to 176)
79
(79 to 79)
NA [1] 
(1 to 1)
[1]
Median values were censored.
14.Secondary Outcome
Title Duration of Stable Disease (SD)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6 0 0 1 0 0 1
Median (Full Range)
Unit of Measure: days
253
(85 to 253)
NA [1] 
(169 to 751)
309
(309 to 309)
134
(134 to 134)
[1]
Median values were censored.
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/6 (50.00%)   10/15 (66.67%)   3/5 (60.00%)   2/3 (66.67%)   1/2 (50.00%)   3/4 (75.00%)   2/2 (100.00%)   2/4 (50.00%) 
Blood and lymphatic system disorders                 
Febrile neutropenia  1  1/6 (16.67%)  6/15 (40.00%)  1/5 (20.00%)  1/3 (33.33%)  1/2 (50.00%)  1/4 (25.00%)  0/2 (0.00%)  1/4 (25.00%) 
Neutropenia  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Anaemia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Gastrointestinal disorders                 
Stomatitis  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Diarrhoea  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Constipation  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hepatobiliary disorders                 
Cholecystitis acute  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Infections and infestations                 
Urinary tract infection  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Clostridium difficile colitis  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/2 (50.00%)  0/4 (0.00%) 
Pneumonia  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Wound infection  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pseudomonas infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/2 (50.00%)  0/4 (0.00%) 
Hypokalaemia  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Bone pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Flank pain  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Tumour haemorrhage  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Metastatic carcinoma of the bladder  1 [1]  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Colorectal cancer  1 [2]  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Metastases to central nervous system  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Cancer pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Nervous system disorders                 
Cerebellar infarction  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Headache  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Psychiatric disorders                 
Confusional state  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                 
Acute kidney injury  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hydronephrosis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haematuria  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Dyspnoea  1 [2]  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders                 
Erythema  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 8.1
[1]
One treatment-emergent death occurred during treatment with MLN8237 20 mg + Docetaxel 75 mg/m^2 and is not related to treatment.
[2]
One treatment-emergent death occurred during treatment with MLN8237 30 mg (5D) + Docetaxel 75 mg/m^2 and is not related to treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   14/15 (93.33%)   5/5 (100.00%)   3/3 (100.00%)   2/2 (100.00%)   4/4 (100.00%)   2/2 (100.00%)   4/4 (100.00%) 
Blood and lymphatic system disorders                 
Neutropenia  1  6/6 (100.00%)  9/15 (60.00%)  5/5 (100.00%)  3/3 (100.00%)  2/2 (100.00%)  4/4 (100.00%)  2/2 (100.00%)  2/4 (50.00%) 
Anaemia  1  2/6 (33.33%)  6/15 (40.00%)  3/5 (60.00%)  3/3 (100.00%)  1/2 (50.00%)  3/4 (75.00%)  1/2 (50.00%)  1/4 (25.00%) 
Leukopenia  1  1/6 (16.67%)  4/15 (26.67%)  2/5 (40.00%)  1/3 (33.33%)  1/2 (50.00%)  2/4 (50.00%)  2/2 (100.00%)  1/4 (25.00%) 
Thrombocytopenia  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Granulocytopenia  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Lymphopenia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Febrile neutropenia  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Lymphadenopathy  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Ear and labyrinth disorders                 
Deafness unilateral  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Tinnitus  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Eye disorders                 
Lacrimation increased  1  0/6 (0.00%)  4/15 (26.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dry eye  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Blepharospasm  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Dacryostenosis acquired  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Glaucoma  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Vision blurred  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders                 
Diarrhoea  1  4/6 (66.67%)  9/15 (60.00%)  1/5 (20.00%)  0/3 (0.00%)  1/2 (50.00%)  1/4 (25.00%)  1/2 (50.00%)  3/4 (75.00%) 
Stomatitis  1  1/6 (16.67%)  9/15 (60.00%)  2/5 (40.00%)  1/3 (33.33%)  0/2 (0.00%)  1/4 (25.00%)  1/2 (50.00%)  4/4 (100.00%) 
Constipation  1  2/6 (33.33%)  4/15 (26.67%)  4/5 (80.00%)  2/3 (66.67%)  0/2 (0.00%)  3/4 (75.00%)  0/2 (0.00%)  1/4 (25.00%) 
Vomiting  1  0/6 (0.00%)  7/15 (46.67%)  2/5 (40.00%)  0/3 (0.00%)  1/2 (50.00%)  2/4 (50.00%)  0/2 (0.00%)  2/4 (50.00%) 
Nausea  1  0/6 (0.00%)  7/15 (46.67%)  3/5 (60.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Abdominal pain  1  1/6 (16.67%)  3/15 (20.00%)  2/5 (40.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  1/4 (25.00%) 
Dyspepsia  1  0/6 (0.00%)  2/15 (13.33%)  3/5 (60.00%)  0/3 (0.00%)  1/2 (50.00%)  1/4 (25.00%)  0/2 (0.00%)  1/4 (25.00%) 
Abdominal pain upper  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Dry mouth  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Dysphagia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Oral pain  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haemorrhoids  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Oral discomfort  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Rectal discharge  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Abdominal discomfort  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Abdominal distension  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dental caries  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Flatulence  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Gastrointestinal inflammation  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haematochezia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Intestinal mass  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Oral mucosal erythema  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Proctalgia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rectal haemorrhage  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Swollen tongue  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
General disorders                 
Fatigue  1  3/6 (50.00%)  10/15 (66.67%)  4/5 (80.00%)  1/3 (33.33%)  2/2 (100.00%)  1/4 (25.00%)  2/2 (100.00%)  2/4 (50.00%) 
Oedema peripheral  1  3/6 (50.00%)  3/15 (20.00%)  1/5 (20.00%)  1/3 (33.33%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  1/4 (25.00%) 
Pyrexia  1  1/6 (16.67%)  1/15 (6.67%)  1/5 (20.00%)  1/3 (33.33%)  1/2 (50.00%)  0/4 (0.00%)  1/2 (50.00%)  1/4 (25.00%) 
Non-cardiac chest pain  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Asthenia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Catheter site erythema  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Catheter site haematoma  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Chest discomfort  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Face oedema  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Influenza like illness  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Thrombosis in device  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hepatobiliary disorders                 
Cholecystitis chronic  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Immune system disorders                 
Seasonal allergy  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Infections and infestations                 
Oral candidiasis  1  1/6 (16.67%)  2/15 (13.33%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  2/4 (50.00%)  1/2 (50.00%)  0/4 (0.00%) 
Upper respiratory tract infection  1  3/6 (50.00%)  3/15 (20.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Fungal skin infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Herpes zoster  1  2/6 (33.33%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pneumonia  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Staphylococcal skin infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Bacteraemia  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Bronchitis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Cellulitis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Clostridium difficile colitis  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Clostridium difficile infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Conjunctivitis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dermatophytosis  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Device related infection  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Fungal infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Genital infection fungal  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Herpes simplex  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Localised infection  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Lower respiratory tract infection  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Onychomycosis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pharyngitis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Phlebitis infective  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rash pustular  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Subcutaneous abscess  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Tooth abscess  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Tooth infection  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Vaginal infection  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Viral upper respiratory tract infection  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Vulvovaginal candidiasis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Vulvovaginal mycotic infection  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Injury, poisoning and procedural complications                 
Stoma site pain  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Skin wound  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Post procedural haematuria  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Laceration  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Incision site pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Arthropod bite  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Skin abrasion  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Post-traumatic pain  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Infusion related reaction  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Fall  1  1/6 (16.67%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Investigations                 
Weight decreased  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Weight increased  1  2/6 (33.33%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Alanine aminotransferase increased  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Aspartate aminotransferase increased  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Blood bilirubin increased  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Blood creatinine increased  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Electrocardiogram QT prolonged  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Urine cytology abnormal  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders                 
Decreased appetite  1  0/6 (0.00%)  4/15 (26.67%)  4/5 (80.00%)  2/3 (66.67%)  1/2 (50.00%)  1/4 (25.00%)  1/2 (50.00%)  3/4 (75.00%) 
Dehydration  1  0/6 (0.00%)  5/15 (33.33%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  2/2 (100.00%)  1/4 (25.00%) 
Hypokalaemia  1  0/6 (0.00%)  5/15 (33.33%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Hypophosphataemia  1  0/6 (0.00%)  3/15 (20.00%)  2/5 (40.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hypomagnesaemia  1  0/6 (0.00%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Hyponatraemia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/2 (50.00%)  0/4 (0.00%) 
Hyperglycaemia  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hypoalbuminaemia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Hypocalcaemia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hypovolaemia  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Fluid overload  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hyperkalaemia  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  1/6 (16.67%)  4/15 (26.67%)  1/5 (20.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Back pain  1  2/6 (33.33%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  2/4 (50.00%) 
Bone pain  1  1/6 (16.67%)  3/15 (20.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Muscle spasms  1  1/6 (16.67%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Myalgia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Muscular weakness  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Musculoskeletal chest pain  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Pain in extremity  1  2/6 (33.33%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Arthritis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Coccydynia  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Flank pain  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Joint stiffness  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Joint swelling  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Musculoskeletal stiffness  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Neck pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Tumour pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Nervous system disorders                 
Dysgeusia  1  4/6 (66.67%)  5/15 (33.33%)  3/5 (60.00%)  1/3 (33.33%)  2/2 (100.00%)  0/4 (0.00%)  0/2 (0.00%)  2/4 (50.00%) 
Neuropathy peripheral  1  4/6 (66.67%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  1/2 (50.00%)  1/4 (25.00%)  0/2 (0.00%)  1/4 (25.00%) 
Peripheral sensory neuropathy  1  3/6 (50.00%)  5/15 (33.33%)  0/5 (0.00%)  0/3 (0.00%)  2/2 (100.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dizziness  1  3/6 (50.00%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  1/2 (50.00%)  0/4 (0.00%) 
Headache  1  1/6 (16.67%)  5/15 (33.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Presyncope  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Lethargy  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Myoclonus  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Peripheral motor neuropathy  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Sinus headache  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Somnolence  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Product Issues                 
Device occlusion  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Psychiatric disorders                 
Anxiety  1  2/6 (33.33%)  0/15 (0.00%)  1/5 (20.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Insomnia  1  1/6 (16.67%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Depression  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  1/2 (50.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Agitation  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                 
Haematuria  1  1/6 (16.67%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Urinary incontinence  1  1/6 (16.67%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Urinary retention  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Bladder pain  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Bladder spasm  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haemorrhage urinary tract  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hydronephrosis  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/4 (0.00%) 
Oliguria  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pollakiuria  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Renal failure  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Dyspnoea  1  1/6 (16.67%)  4/15 (26.67%)  1/5 (20.00%)  2/3 (66.67%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  1/4 (25.00%) 
Cough  1  2/6 (33.33%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  2/2 (100.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Epistaxis  1  2/6 (33.33%)  2/15 (13.33%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Oropharyngeal pain  1  1/6 (16.67%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Atelectasis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haemoptysis  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rhinorrhoea  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Sinus congestion  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Asthma  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dysphonia  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haemothorax  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hypoxia  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Laryngeal oedema  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Nasal congestion  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Paranasal sinus hypersecretion  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pharyngeal inflammation  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pleural effusion  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pleuritic pain  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rhinalgia  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rhinitis allergic  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Tachypnoea  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Throat irritation  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Upper-airway cough syndrome  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders                 
Alopecia  1  3/6 (50.00%)  7/15 (46.67%)  3/5 (60.00%)  1/3 (33.33%)  2/2 (100.00%)  1/4 (25.00%)  1/2 (50.00%)  2/4 (50.00%) 
Rash  1  3/6 (50.00%)  3/15 (20.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Nail disorder  1  0/6 (0.00%)  3/15 (20.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rash papular  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Onycholysis  1  3/6 (50.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rash macular  1  1/6 (16.67%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Rash pruritic  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  2/2 (100.00%)  0/4 (0.00%) 
Nail discolouration  1  1/6 (16.67%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pruritus  1  0/6 (0.00%)  1/15 (6.67%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Dermatitis contact  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Night sweats  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Rash maculo-papular  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Skin exfoliation  1  0/6 (0.00%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Cold sweat  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dermal cyst  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dermatitis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dermatitis allergic  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Dry skin  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Ecchymosis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Eczema  1  0/6 (0.00%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/4 (25.00%) 
Exfoliative rash  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hyperhidrosis  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Intertrigo  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Onychalgia  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Petechiae  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pruritus generalised  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Vascular disorders                 
Hypotension  1  0/6 (0.00%)  3/15 (20.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  2/2 (100.00%)  0/4 (0.00%) 
Hypertension  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Lymphoedema  1  1/6 (16.67%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Embolism  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Haematoma  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Hot flush  1  0/6 (0.00%)  0/15 (0.00%)  1/5 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Orthostatic hypotension  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Pallor  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Phlebitis  1  0/6 (0.00%)  1/15 (6.67%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Thrombophlebitis superficial  1  1/6 (16.67%)  0/15 (0.00%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Flushing  1  1/6 (16.67%)  2/15 (13.33%)  0/5 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/4 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 8.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01094288     History of Changes
Other Study ID Numbers: C14009
First Submitted: March 17, 2010
First Posted: March 26, 2010
Results First Submitted: January 4, 2018
Results First Posted: February 15, 2019
Last Update Posted: February 15, 2019