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A Study to Evaluate TAK-931 in Participants With Advanced Nonhematologic Tumors

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ClinicalTrials.gov Identifier: NCT02699749
Recruitment Status : Completed
First Posted : March 4, 2016
Results First Posted : February 21, 2021
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Nonhematologic Neoplasms, Advanced
Intervention Drug: TAK-931
Enrollment 80
Recruitment Details Participants took part in the study at 2 investigative sites in Japan from 24 March 2016 to 21 December 2019.
Pre-assignment Details Participants with advanced nonhematological solid tumors were enrolled to receive TAK-931 in 1 of the 4 treatment schedules: Schedule A, Schedule B, Schedule D and Schedule E. Schedules C and F were not conducted due to business reasons.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description TAK-931 30 milligram (mg), capsule, orally, once daily (QD) for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily or twice daily (BID) for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Period Title: Overall Study
Started 3 3 16 3 3 9 6 6 6 6 6 4 3 6
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 3 3 16 3 3 9 6 6 6 6 6 4 3 6
Reason Not Completed
Other             0             0             2             0             0             1             1             0             0             0             1             0             0             0
Progressive Disease             3             3             14             3             3             7             5             5             6             6             5             4             3             5
Death             0             0             0             0             0             0             0             0             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             0             1             0             1             0             0             0             0             0             0
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg Total
Hide Arm/Group Description TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. Total of all reporting groups
Overall Number of Baseline Participants 3 3 16 3 3 9 6 6 6 6 6 4 3 6 80
Hide Baseline Analysis Population Description
The safety population was defined as all participants who received any amount of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
62.7  (6.81) 56.7  (2.52) 57.4  (11.99) 59.3  (1.53) 61.7  (3.21) 52.4  (13.45) 50.0  (8.15) 59.8  (12.01) 59.3  (6.56) 62.7  (8.09) 58.3  (17.41) 59.5  (2.38) 60.7  (13.58) 62.8  (12.40) 58.1  (10.74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
Female
0
   0.0%
2
  66.7%
5
  31.3%
3
 100.0%
1
  33.3%
5
  55.6%
1
  16.7%
2
  33.3%
3
  50.0%
3
  50.0%
2
  33.3%
2
  50.0%
2
  66.7%
1
  16.7%
32
  40.0%
Male
3
 100.0%
1
  33.3%
11
  68.8%
0
   0.0%
2
  66.7%
4
  44.4%
5
  83.3%
4
  66.7%
3
  50.0%
3
  50.0%
4
  66.7%
2
  50.0%
1
  33.3%
5
  83.3%
48
  60.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
 100.0%
3
 100.0%
16
 100.0%
3
 100.0%
3
 100.0%
9
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
4
 100.0%
3
 100.0%
6
 100.0%
80
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Japan Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
3
 100.0%
3
 100.0%
16
 100.0%
3
 100.0%
3
 100.0%
9
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
4
 100.0%
3
 100.0%
6
 100.0%
80
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
169.67  (8.663) 159.70  (7.076) 165.39  (6.727) 155.03  (4.306) 162.80  (11.012) 163.64  (9.107) 168.73  (7.387) 167.40  (9.586) 160.08  (12.071) 156.43  (8.913) 163.87  (7.469) 162.43  (9.280) 155.90  (12.612) 165.92  (8.817) 163.41  (8.890)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
70.07  (18.269) 55.33  (3.099) 62.06  (10.535) 50.53  (3.707) 58.03  (8.686) 66.51  (16.750) 71.00  (10.769) 65.85  (10.783) 59.63  (16.675) 51.08  (10.167) 56.25  (13.248) 61.30  (13.851) 53.27  (13.250) 58.55  (13.772) 60.91  (12.964)
Body Surface Area (BSA)  
Median (Standard Deviation)
Unit of measure:  Square meter (m˄2)
Number Analyzed 3 participants 3 participants 16 participants 3 participants 3 participants 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants 4 participants 3 participants 6 participants 80 participants
1.810  (0.2805) 1.563  (0.0757) 1.684  (0.1513) 1.473  (0.0569) 1.617  (0.1620) 1.732  (0.2538) 1.820  (0.1510) 1.747  (0.1904) 1.620  (0.2922) 1.485  (0.1660) 1.595  (0.2134) 1.658  (0.2323) 1.513  (0.2501) 1.637  (0.2284) 1.656  (0.2095)
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs) Assessed by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Version 4.03
Hide Description Toxicity was evaluated by NCI CTCAE v4.03. DLT:any of following occurred events during Cycle 1 considered by investigator to be possibly related to therapy:1)Grade4 neutropenia,2)Febrile neutropenia lasting greater(>)1 hour,3)Grade greater than or equal to (>=)3 neutropenia with infection,4)Grade >=3 thrombocytopenia with bleeding,4)Grade 4 thrombocytopenia,5)delay in initiation of Cycle 2 by >14 days,6)Grade 2:<Grade 2 ejection fraction,7)other Grade 2 nonhematologic toxicities considered by investigator related to study drug and DLTs,8)who received <50 percent of doses of planned TAK-931 dosing in Cycle 1 for related AEs:<7 QD/<14 BID doses (Schedules A,B);<11 QD/<21 BID doses(Schedule D),<3 QD/<6 BID doses for(Schedule E),9)Grade >=3 nonhematologic toxicity except arthralgia/myalgia and fatigue, isolated >=Grade 3 laboratory abnormalities if it is asymptomatic and resolves to <=Grade 1 or baseline levels in <=7 days;inadequately treated Grade 3 nausea and/or vomiting and diarrhea.
Time Frame Baseline up to Cycle 1 (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The DLT-evaluable population was defined as all participants who received at least 75% of their planned TAK-931 doses for their first cycle of treatment (unless interrupted by study drug-related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 16 3 3 9 6 6 6 6 6 4 3 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2
  66.7%
0
   0.0%
2
  22.2%
1
  16.7%
1
  16.7%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
2
  33.3%
2.Primary Outcome
Title Number of Participants With Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (up to Day 499)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who received any amount of study drug.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 16 3 3 9 6 6 6 6 6 4 3 6
Measure Type: Count of Participants
Unit of Measure: Participants
3
 100.0%
3
 100.0%
16
 100.0%
3
 100.0%
3
 100.0%
9
 100.0%
6
 100.0%
6
 100.0%
5
  83.3%
6
 100.0%
6
 100.0%
4
 100.0%
3
 100.0%
6
 100.0%
3.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration After First Dose of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
133
(22.6%)
229
(14.3%)
214
(40.9%)
265
(9.8%)
277
(19.0%)
302
(31.7%)
402
(24.5%)
454
(49.2%)
98.3
(37.0%)
149
(39.8%)
197
(31.5%)
462
(36.1%)
514
(15.9%)
499
(23.3%)
4.Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After First Dose of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Median (Full Range)
Unit of Measure: hours
0.97
(0.93 to 1.93)
1.05
(0.97 to 2.30)
1.93
(0.45 to 2.13)
3.88
(2.08 to 4.12)
1.00
(0.42 to 1.03)
4.00
(1.00 to 4.20)
1.36
(0.47 to 3.98)
1.05
(0.45 to 4.02)
1.00
(0.93 to 2.17)
2.13
(0.47 to 2.15)
1.92
(0.87 to 3.95)
2.00
(1.05 to 2.07)
3.82
(1.88 to 4.05)
2.07
(1.97 to 4.10)
5.Secondary Outcome
Title AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After First Dose of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanogram per milliliter (h*ng/mL)
737
(24.1%)
1250
(14.6%)
1240
(31.8%)
2000
(33.8%)
1470
(17.9%)
2140
(35.9%)
2240
(23.9%)
2740
(29.5%)
494
(52.5%)
801
(32.3%)
1100
(28.2%)
2720
(20.0%)
3760
(48.9%)
3870
(35.9%)
6.Secondary Outcome
Title AUC12: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours After Multiple Doses of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
641
(22.2%)
1110
(13.4%)
1070
(29.9%)
1670
(30.5%)
1270
(12.2%)
1800
(32.8%)
1970
(23.2%)
2360
(28.8%)
431
(49.9%)
693
(30.3%)
956
(27.0%)
2280
(23.8%)
3110
(42.8%)
3160
(30.3%)
7.Secondary Outcome
Title AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After First Dose of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
742
(24.3%)
1250
(14.7%)
1250
(32.0%)
2010
(34.0%)
1480
(17.7%)
2160
(36.0%)
2240
(23.7%)
2750
(29.5%)
491
(53.3%)
805
(32.4%)
1100
(28.2%)
2730
(20.5%)
3770
(49.3%)
3880
(35.8%)
8.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 9 6 6 6 6 6 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
133
(21.8%)
239
(16.2%)
231
(28.7%)
330
(23.9%)
218
(4.4%)
341
(54.0%)
380
(15.6%)
671
(73.6%)
104
(53.4%)
160
(34.1%)
193
(20.7%)
532
(39.9%)
654
(40.7%)
917
(22.1%)
9.Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Multiple Doses of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
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Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 14 3 3 8 6 6 6 6 5 4 3 6
Median (Full Range)
Unit of Measure: hours
2.02
(0.43 to 2.07)
1.00
(0.93 to 1.90)
1.91
(0.95 to 3.88)
1.95
(0.92 to 2.08)
2.00
(0.50 to 2.17)
2.01
(0.90 to 3.90)
1.90
(1.00 to 4.12)
1.92
(0.98 to 4.12)
1.50
(0.97 to 2.02)
2.00
(0.9 to 3.97)
1.08
(0.92 to 2.13)
1.49
(0.95 to 4.07)
2.07
(1.9 to 2.18)
2.08
(0.92 to 2.20)
10.Secondary Outcome
Title AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After Multiple Doses of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
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Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 14 3 3 8 6 6 6 6 5 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
799
(19.3%)
1400
(15.4%)
1320
(33.6%)
2210
(30.5%)
1650
(10.4%)
2220
(39.8%)
2620
(26.8%)
4410
(81.8%)
600
(49.1%)
958
(46.1%)
1140
(41.2%)
3760
(28.6%)
4830
(55.6%)
6260
(32.2%)
11.Secondary Outcome
Title AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Multiple Doses of TAK-931
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B])
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 14 3 3 8 6 6 6 6 5 4 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
805
(19.4%)
1410
(15.0%)
1330
(33.9%)
2220
(30.8%)
1650
(10.4%)
2230
(39.8%)
2630
(27.4%)
4420
(81.0%)
603
(49.2%)
964
(46.4%)
1150
(41.3%)
3770
(28.7%)
4840
(55.8%)
6280
(32.2%)
12.Secondary Outcome
Title Schedule A, B and D: Change From Baseline in Phosphorylated Minichromosome Maintenance Complex-2 (pMCM2) (Ser40) Levels in Skin Based on Histological Score Nuclei (H-score) After Multiple Doses Of TAK-931
Hide Description H-score were a composite score that comprised of intensity and percentage of staining and were used for assessing amount of protein (in this case pMCM2 [Ser40]) present in a tissue sample. The composite score obtained by H-score is derived by adding of the percentages of cell staining at each intensity level multiplied by the weighted intensity of staining (0 [no staining], 1+ [weak staining], 2+ [medium staining], 3+ [strong staining]). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of pMCM2 (Ser40) in the tissue sample, while higher scores represent stronger expression of pMCM2 (Ser40) in the tissue samples.
Time Frame Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days)
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Hide Analysis Population Description
Pharmacodynamics population: all participants who received at least the first dose of TAK-931, had a baseline skin punch biopsy sample, and had at least 1 additional postbaseline skin punch biopsy sample. Overall number analyzed "N": participants who were evaluable for the outcome measure. Number analyzed "n": participants who were evaluable for this outcome measure for given categories. Data for this outcome measure was not collected and analyzed for Schedule E Cohorts due to business reasons.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 16 3 3 9 0 0 6 6 0
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 3 participants 3 participants 14 participants 3 participants 3 participants 5 participants 0 participants 0 participants 6 participants 3 participants 0 participants
18.467  (8.4506) 19.533  (3.7754) 10.500  (5.8477) 10.933  (1.9425) 4.400  (2.9597) 12.720  (2.0229) 22.050  (24.5239) 33.317  (23.4266)
Schedule B: Change at Cycle 1 Day 7 Number Analyzed 0 participants 0 participants 0 participants 0 participants 3 participants 5 participants 0 participants 0 participants 0 participants 0 participants 0 participants
-3.733  (3.1770) -9.180  (7.2589)
Schedule A and D: Change at Cycle 1 Day 8 Number Analyzed 3 participants 3 participants 14 participants 3 participants 0 participants 0 participants 0 participants 0 participants 4 participants 3 participants 0 participants
-7.533  (2.9280) -6.667  (10.5078) -6.743  (8.7444) -9.933  (2.2030) -5.900  (4.2379) -26.883  (24.5978)
Schedule D: Change at Cycle 1 Day 12 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants 0 participants
-67.100
13.Secondary Outcome
Title Schedule A, B and D: Change From Baseline in pMCM2 (Ser40) Levels in Skin Based on Positive Index After Multiple Doses Of TAK-931
Hide Description Positive index was calculated by taking the number of cells staining positive for the marker over the total number of cells.
Time Frame Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics population: all participants who received at least the first dose of TAK-931, had a baseline skin punch biopsy sample, and had at least 1 additional postbaseline skin punch biopsy sample. Overall number analyzed "N": participants who were evaluable for the outcome measure. Number analyzed "n": participants who were evaluable for this outcome measure for given categories. Data for this outcome measure was not collected and analyzed for Schedule E Cohorts due to business reasons.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 16 3 3 9 0 0 6 6 0
Mean (Standard Deviation)
Unit of Measure: percentage of cell
Baseline Number Analyzed 3 participants 3 participants 14 participants 3 participants 3 participants 5 participants 0 participants 0 participants 6 participants 3 participants 0 participants
0.08600  (0.039950) 0.08533  (0.019425) 0.04429  (0.021780) 0.04800  (0.006928) 0.02000  (0.013856) 0.05080  (0.007694) 0.10217  (0.126757) 0.15200  (0.128829)
Schedule B: Change at Cycle 1 Day 7 Number Analyzed 0 participants 0 participants 0 participants 0 participants 3 participants 5 participants 0 participants 0 participants 0 participants 0 participants 0 participants
-0.01667  (0.015144) -0.01916  (0.063995)
Schedule A and D: Change at Cycle 1 Day 8 Number Analyzed 3 participants 3 participants 14 participants 3 participants 0 participants 0 participants 0 participants 0 participants 4 participants 3 participants 0 participants
-0.03037  (0.014191) -0.02386  (0.046889) -0.02643  (0.033014) -0.04125  (0.008245) -0.02150  (0.018930) -0.12436  (0.134410)
Schedule D: Change at Cycle 1 Day 12 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants 0 participants
-0.33900
14.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR was defined as percentage of participants who had achieved complete response (CR) and partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V 1.1). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
Time Frame From date of first dose to the date of first documentation of progressive disease (PD) or death due to any cause, which ever occurred first (up to Month 45)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population is defined as participants who receive at least 1 dose of study drug, have measurable disease at baseline, and at least 1 post-baseline response assessment. Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 15 3 3 8 6 6 6 5 6 3 3 5
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33
(1 to 91)
0
(0 to 71)
7
(0 to 32)
33
(1 to 91)
0
(0 to 71)
0
(0 to 37)
17
(0 to 64)
17
(0 to 64)
0
(0 to 46)
0
(0 to 52)
0
(0 to 46)
0
(0 to 71)
0
(0 to 71)
0
(0 to 52)
15.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from the date of first dose to the date of first documentation of PD or death due to any cause, whichever occurs first, as measured by RECIST V1.1. PD: 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method.
Time Frame From date of first dose to the date of first documentation of PD or death due to any cause, which ever occurred first (up to Month 45)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who received any amount of study drug.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 3 3 16 3 3 9 6 6 6 6 6 4 3 6
Median (95% Confidence Interval)
Unit of Measure: months
4.2
(1.74 to 9.20)
2.1
(0.53 to 3.29)
2.0
(1.68 to 5.32)
4.8
(3.32 to 6.34)
3.1
(0.92 to 5.85)
2.8
(1.58 to 3.25)
2.1
(0.79 to 6.21)
4.2
(1.84 to 6.64)
1.9
(1.41 to 2.10)
3.9
(1.91 to 8.05)
2.1
(1.18 to 15.24)
1.9
(0.39 to 3.91)
1.9
(1.05 to 4.37)
2.6
(0.53 to 5.88)
16.Secondary Outcome
Title Duration of Response (DOR)
Hide Description The DOR was defined as the time from the date of first documentation of a response (CR or PR) to the date of first documentation of PD, as measured by RECIST V 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: was at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD. PD: 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. DOR was analyzed using the Kaplan-Meier method.
Time Frame From the date of first documentation of response to the date of first documentation of PD (up to Month 45)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population is defined as participants who receive at least 1 dose of study drug, have measurable disease at baseline, and at least 1 post-baseline response assessment. Responders without documentation of PD were censored at the date of last response assessment that is stable disease or better.
Arm/Group Title Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description:
TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
Overall Number of Participants Analyzed 1 0 1 1 0 0 1 1 0 0 0 0 0 0
Mean (Standard Deviation)
Unit of Measure: months
2.1 2.7 2.2 4.2 0.0
Time Frame TEAEs are adverse events (AEs) that started after the first dose of study drug through 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (whichever occurred first) (up to Day 499)
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 Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Hide Arm/Group Description TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor.
All-Cause Mortality
Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   0/3 (0.00%)   0/3 (0.00%)   0/16 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   0/9 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   1/6 (16.67%) 
Hide Serious Adverse Events
Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   0/3 (0.00%)   1/3 (33.33%)   5/16 (31.25%)   2/3 (66.67%)   1/3 (33.33%)   2/9 (22.22%)   1/6 (16.67%)   1/6 (16.67%)   1/6 (16.67%)   1/6 (16.67%)   3/6 (50.00%)   2/4 (50.00%)   0/3 (0.00%)   3/6 (50.00%) 
Blood and lymphatic system disorders                             
Neutropenias 0 1 (33) 0 1  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  2/9 (22.22%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  2/9 (22.22%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                             
Gastrointestinal stenosis and obstruction NEC  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ileus  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Duodenal and small intestinal stenosis and obstruction  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Duodenal obstruction  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal inflammatory disorders NEC  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Enterocolitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nausea and vomiting symptoms  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nausea  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
General disorders                             
Asthenic conditions  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Malaise  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Infections and infestations                             
Sepsis, bacteraemia, viraemia and fungaemia NEC  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Sepsis  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal and gastrointestinal infections  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Lower respiratory tract and lung infections  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Metabolism and nutrition disorders                             
Appetite disorders  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Decreased appetite  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                             
Oncologic complications and emergencies  1  0/3 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  1/6 (16.67%) 
Malignant ascites  1  0/3 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Malignant pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Tumour pain  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Mediastinal neoplasms malignant  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Thymoma malignant  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Metastases to specified sites  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Lymphangiosis carcinomatosa  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pancreatic neoplasms malignant (excl islet cell and carcinoid)  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pancreatic carcinoma  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                             
Central nervous system haemorrhages and cerebrovascular accidents  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cerebrovascular accident  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Increased intracranial pressure disorders  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Brain oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Seizures and seizure disorders NEC  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Seizure  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders                             
Urinary abnormalities  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Haematuria  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                             
Lower respiratory tract inflammatory and immunologic conditions  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pneumonia aspiration  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pneumothorax and pleural effusions NEC  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pleural effusion  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Schedule A: TAK-931 30 mg Schedule A: TAK-931 40 mg Schedule A: TAK-931 50 mg Schedule A: TAK-931 60 mg Schedule B: TAK-931 60 mg Schedule B: TAK-931 80 mg Schedule B: TAK-931 100 mg Schedule B: TAK-931 120 mg Schedule D: TAK-931 20 mg Schedule D: TAK-931 30 mg Schedule D: TAK-931 40 mg Schedule E: TAK-931 100 mg Schedule E: TAK-931 120 mg Schedule E: TAK-931 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   3/3 (100.00%)   3/3 (100.00%)   16/16 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   9/9 (100.00%)   6/6 (100.00%)   6/6 (100.00%)   5/6 (83.33%)   6/6 (100.00%)   6/6 (100.00%)   4/4 (100.00%)   3/3 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders                             
Neutropenia  1  1/3 (33.33%)  1/3 (33.33%)  8/16 (50.00%)  2/3 (66.67%)  1/3 (33.33%)  7/9 (77.78%)  5/6 (83.33%)  6/6 (100.00%)  1/6 (16.67%)  2/6 (33.33%)  3/6 (50.00%)  1/4 (25.00%)  2/3 (66.67%)  5/6 (83.33%) 
Anaemia  1  0/3 (0.00%)  1/3 (33.33%)  4/16 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/9 (11.11%)  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  4/6 (66.67%) 
Leukopenia  1  0/3 (0.00%)  1/3 (33.33%)  3/16 (18.75%)  1/3 (33.33%)  1/3 (33.33%)  5/9 (55.56%)  5/6 (83.33%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Lymphopenia  1  0/3 (0.00%)  1/3 (33.33%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  2/9 (22.22%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  0/9 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Lymphadenitis  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cardiac disorders                             
Electrocardiogram QT prolonged  1  0/3 (0.00%)  1/3 (33.33%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Cardiomyopathy  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Stress cardiomyopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Supraventricular tachycardia  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ear and labyrinth disorders                             
Vertigo  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Eye disorders                             
Abnormal sensation in eye  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Cataract  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Dry eye  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vision blurred  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                             
Nausea  1  0/3 (0.00%)  2/3 (66.67%)  10/16 (62.50%)  3/3 (100.00%)  1/3 (33.33%)  9/9 (100.00%)  5/6 (83.33%)  6/6 (100.00%)  0/6 (0.00%)  3/6 (50.00%)  2/6 (33.33%)  1/4 (25.00%)  2/3 (66.67%)  4/6 (66.67%) 
Vomiting  1  0/3 (0.00%)  1/3 (33.33%)  4/16 (25.00%)  2/3 (66.67%)  0/3 (0.00%)  7/9 (77.78%)  2/6 (33.33%)  4/6 (66.67%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  1/4 (25.00%)  2/3 (66.67%)  4/6 (66.67%) 
Diarrhoea  1  0/3 (0.00%)  1/3 (33.33%)  5/16 (31.25%)  1/3 (33.33%)  0/3 (0.00%)  2/9 (22.22%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  3/6 (50.00%) 
Constipation  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/9 (22.22%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/9 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Malaise  1  1/3 (33.33%)  0/3 (0.00%)  3/16 (18.75%)  1/3 (33.33%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  1/6 (16.67%) 
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  3/9 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ascites  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ileus  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Angular cheilitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Duodenal obstruction  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastritis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrooesophageal reflux disease  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Haemorrhoids  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Large intestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Lip dry  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pancreatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Tooth loss  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
General disorders                             
Fatigue  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  2/3 (66.67%)  1/9 (11.11%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  2/6 (33.33%) 
Oedema peripheral  1  0/3 (0.00%)  1/3 (33.33%)  3/16 (18.75%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  2/3 (66.67%)  1/6 (16.67%) 
Pyrexia  1  2/3 (66.67%)  0/3 (0.00%)  3/16 (18.75%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/6 (16.67%) 
Application site pruritus  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Face oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Influenza like illness  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Infusion site extravasation  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Non-cardiac chest pain  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders                             
Bile duct obstruction  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cholangitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hepatic function abnormal  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Hepatomegaly  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Infections and infestations                             
Nasopharyngitis  1  1/3 (33.33%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  3/9 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pneumonia  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Upper respiratory tract infection  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Urinary tract infection  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Bronchitis bacterial  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Conjunctivitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cystitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Eye infection  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Oral candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Oral herpes  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Periodontitis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                             
Fall  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  1/6 (16.67%) 
Contusion  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Radiation skin injury  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Tooth fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Investigations                             
White blood cell count decreased  1  1/3 (33.33%)  0/3 (0.00%)  6/16 (37.50%)  1/3 (33.33%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  4/6 (66.67%)  1/6 (16.67%)  3/6 (50.00%)  3/6 (50.00%)  1/4 (25.00%)  1/3 (33.33%)  5/6 (83.33%) 
Blood creatinine increased  1  0/3 (0.00%)  1/3 (33.33%)  2/16 (12.50%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Platelet count decreased  1  0/3 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Aspartate aminotransferase increased  1  1/3 (33.33%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gamma-glutamyltransferase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/6 (0.00%) 
Blood bilirubin increased  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Lymphocyte count decreased  1  0/3 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Alanine aminotransferase increased  1  1/3 (33.33%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/6 (16.67%) 
Brain natriuretic peptide increased  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Weight decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Weight increased  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders                             
Decreased appetite  1  0/3 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  2/9 (22.22%)  1/6 (16.67%)  2/6 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  0/4 (0.00%)  1/3 (33.33%)  4/6 (66.67%) 
Hypoalbuminaemia  1  0/3 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  1/3 (33.33%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypophosphataemia  1  1/3 (33.33%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Hypokalaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypocalcaemia  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypoglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hyperglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypermagnesaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                             
Arthralgia  1  0/3 (0.00%)  1/3 (33.33%)  1/16 (6.25%)  1/3 (33.33%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Back pain  1  1/3 (33.33%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neck pain  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Arthritis  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Myalgia  1  0/3 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                             
Tumour pain  1  0/3 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  2/3 (66.67%)  0/6 (0.00%) 
Cancer pain  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                             
Dysgeusia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Dementia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Headache  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Seizure  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Somnolence  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Vagus nerve disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Psychiatric disorders                             
Insomnia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Renal and urinary disorders                             
Hydronephrosis  1  0/3 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypertonic bladder  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                             
Cough  1  1/3 (33.33%)  1/3 (33.33%)  0/16 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Dysphonia  1  0/3 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)