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A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02045095
Recruitment Status : Terminated
First Posted : January 24, 2014
Results First Posted : March 14, 2019
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced Malignant Solid Tumors
Intervention Drug: MLN7243
Enrollment 29
Recruitment Details Participants took part in the study at 7 investigative sites in the United States from 31 January 2014 to 09 November 2016.
Pre-assignment Details Participants with diagnosis of advanced malignant solid tumors were enrolled in Schedule A of dose escalation phase to receive TAK-243 (MLN7243). The study was terminated prior to start of Schedule B of dose escalation phase and planned expansion because of realignment of the sponsor's pipeline program.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Period Title: Overall Study
Started 3 4 4 4 5 8 1
Completed 0 0 0 0 0 0 0
Not Completed 3 4 4 4 5 8 1
Reason Not Completed
Other             0             0             1             0             0             2             0
Progressive Disease             3             3             2             4             2             4             1
Withdrawal by Subject             0             0             0             0             3             0             0
Adverse Event             0             1             1             0             0             2             0
Arm/Group Title Schedule A: TAK-243 Total
Hide Arm/Group Description TAK-243 1 mg, 2 mg, 4 mg, 8 mg, 12 mg, 18 mg, and 4mg homozygous mutant, infusion, IV over 10-minutes, twice-weekly on Days 1, 4, 8, and 11 in a 21-day treatment cycle for a maximum of 12 cycles, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Baseline Participants 29
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants
56.8  (9.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
Female
12
  41.4%
Male
17
  58.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
Hispanic or Latino
2
   6.9%
Not Hispanic or Latino
22
  75.9%
Unknown or Not Reported
5
  17.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
5
  17.2%
White
22
  75.9%
More than one race
0
   0.0%
Unknown or Not Reported
2
   6.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 29 participants
29
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 29 participants
170.88  (12.101)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 29 participants
79.69  (16.829)
Body Surface Area  
Mean (Standard Deviation)
Unit of measure:  Square meter (m^2)
Number Analyzed 29 participants
1.936  (0.2364)
1.Primary Outcome
Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
TEAEs 3 4 4 4 4 8 1
SAEs 1 1 2 2 1 4 0
2.Primary Outcome
Title Number of Participants With Laboratory Related TEAEs by System Organ Class (SOC)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
Metabolism and nutrition disorders 1 1 1 3 1 4 1
Blood and lymphatic system disorders 1 1 1 2 0 4 0
Investigations 1 1 2 0 0 1 0
3.Primary Outcome
Title Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
Pyrexia 0 0 0 0 0 1 0
Dyspnoea 0 0 1 0 0 2 0
Dyspnoea exertional 0 0 0 0 0 1 0
Hypertension 0 0 1 0 0 1 0
4.Primary Outcome
Title Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 up to Cycle 1 Day 11
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0 0
5.Primary Outcome
Title Number of Participants With Clinically Significant Echocardiogram Abnormalities
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 up to 30 days after last dose of study drug (Cycle 10 Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0 0
6.Primary Outcome
Title Number of Participants With TEAEs Related to Tropinin I and T
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of TAK-243.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Measure Type: Number
Unit of Measure: participants
0 0 1 0 0 0 0
7.Secondary Outcome
Title Ceoi: Plasma Concentration at the End of Infusion for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 and 11: pre-infusion to end of infusion (up to 10 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma pharmacokinetic (PK) analysis population where data at specified time points was available.The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Cycle 1 Day 1 Number Analyzed 3 participants 3 participants 4 participants 4 participants 4 participants 8 participants 1 participants
78.658  (48.2212) 100.758  (24.0669) 473.075  (132.7667) 921.804  (258.6109) 1276.684  (804.4476) 1775.470  (463.8601) 391.000 [1]   (NA)
Cycle 1 Day 11 Number Analyzed 3 participants 4 participants 3 participants 3 participants 3 participants 7 participants 1 participants
68.073  (35.2718) 129.681  (52.4680) 273.807  (179.4241) 2299.438  (9027.7420) 1271.199  (628.4555) 2316.282  (7744.9842) 265.000 [1]   (NA)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
8.Secondary Outcome
Title AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: nanogram hours per milliliter (ng*hr/mL)
Cycle 1 Day 1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 2 participants 5 participants 0 participants
32.853  (17.3894) 52.845  (5.6656) 312.714  (193.3829) 368.071  (8.2218) 867.427  (374.1800) 922.068  (192.2359)
Cycle 1 Day 11 Number Analyzed 3 participants 4 participants 1 participants 0 participants 0 participants 0 participants 1 participants
30.181  (12.8884) 50.337  (8.9494) 178.142 [1]   (NA) 228.053 [1]   (NA)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
9.Secondary Outcome
Title AUCτ: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 5 participants 0 participants
535.581 [1]   (NA) 377.812 [1]   (NA) 1132.160 [1]   (NA) 922.059  (192.1773)
Cycle 1 Day 11 Number Analyzed 0 participants 0 participants 0 participants 1 participants 3 participants 5 participants 0 participants
506.693 [1]   (NA) 663.176  (261.1957) 771.491  (181.7875)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
10.Secondary Outcome
Title AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1 Number Analyzed 0 participants 0 participants 2 participants 2 participants 3 participants 4 participants 0 participants
203.043  (10.0600) 375.541  (11.2872) 579.122  (201.1755) 768.728  (174.9927)
Cycle 1 Day 11 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 3 participants 0 participants
179.726 [1]   (NA) 509.785 [1]   (NA) 752.152 [1]   (NA) 864.533  (175.9351)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
11.Secondary Outcome
Title CL: Total Clearance After Intravenous Administration for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: liter per hour (L/hr)
Cycle 1 Day 1 Number Analyzed 0 participants 0 participants 2 participants 2 participants 3 participants 4 participants 0 participants
19.724  (0.9773) 21.312  (0.6406) 22.749  (8.8967) 24.379  (5.6587)
Cycle 1 Day 11 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 3 participants 0 participants
22.162 [1]   (NA) 15.789 [1]   (NA) 16.194 [1]   (NA) 21.558  (4.8376)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
12.Secondary Outcome
Title Vss: Volume of Distribution at Steady State for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: liter
Cycle 1 Day 1 Number Analyzed 0 participants 0 participants 2 participants 2 participants 3 participants 4 participants 0 participants
29.806  (0.9494) 33.957  (5.8273) 37.596  (20.7520) 63.744  (39.5945)
Cycle 1 Day 11 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 3 participants 0 participants
34.120 [1]   (NA) 39.618 [1]   (NA) 56.573 [1]   (NA) 51.806  (18.8787)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
13.Secondary Outcome
Title Aet: Amount of TAK-243 Excreted Unchanged in Urine
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1; Cycle 1 Day 11
Hide Outcome Measure Data
Hide Analysis Population Description
No data were collected as no participant was analyzed since study was terminated before the planned expansion phase.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Fet: Percentage of TAK-243 Excreted Unchanged in Urine
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1; Cycle 1 Day 11
Hide Outcome Measure Data
Hide Analysis Population Description
No data were collected as no participant was analyzed since study was terminated before the planned expansion phase.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Terminal Phase Elimination Half-life (T1/2) for TAK-243
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The plasma PK analysis population where data at specified time points was available. The plasma PK-evaluable population included all participants who have sufficient dosing and concentration-time data to reliably estimate PK parameters.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 4 4 5 8 1
Mean (Standard Deviation)
Unit of Measure: hour
Cycle 1 Day 1 Number Analyzed 0 participants 0 participants 2 participants 2 participants 3 participants 4 participants 0 participants
7.001  (1.4372) 9.377  (4.6442) 5.765  (0.8607) 8.296  (4.3573)
Cycle 1 Day 11 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 3 participants 0 participants
5.572 [1]   (NA) 15.212 [1]   (NA) 27.446 [1]   (NA) 9.873  (6.3030)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
16.Secondary Outcome
Title Change From Baseline in Immunohistochemistry (IHC) Biomarkers in Tumor Biopsies at Cycle 1 Day 12 (C1D12) as Assessed by Histological Score (H-score)
Hide Description The pharmacodynamics IHC biomarkers included polyubiquitin marker and ubquityl (Ub)-histone H2B marker. H-score was a composite score that comprised of intensity and percentage of staining and was used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.
Time Frame Baseline and Cycle 1 Day 12
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic population:baseline,post-baseline assessments were available,including all participants who received all doses(Cycle 1),have pre-post dose paired tumor tissue biopsies taken at protocol-specified timepoints,have sufficient tumor content at both timepoints to estimate changes in Pharmacodynamic biomarker percent area positive values.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 1 1 1 0 0 0 0
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline: Polyubiquitin H-score 286.00 [1]   (NA) 297.80 [1]   (NA) 282.00 [1]   (NA)
Change at C1D12: Polyubiquitin H-score -3.60 [1]   (NA) -2.00 [1]   (NA) 4.20 [1]   (NA)
Baseline: Ub-histone H2B H-score 269.750 [1]   (NA) 291.000 [1]   (NA) 290.750 [1]   (NA)
Change at C1D12: Ub-histone H2B H-score 13.250 [1]   (NA) 3.250 [1]   (NA) 2.000 [1]   (NA)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
17.Secondary Outcome
Title Change From Baseline in IHC Biomarkers in Tumor Biopsies at C1D12 as Assessed by Positive Index
Hide Description The pharmacodynamics IHC biomarkers included polyubiquitin marker and Ub-histone H2B marker. Positive index was calculated by taking the number of positive cells over the total number of cells.
Time Frame Baseline and Cycle 1 Day 12
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic population:baseline,post-baseline assessments were available,including all participants who received all doses(Cycle 1),have pre-post dose paired tumor tissue biopsies taken at protocol-specified timepoints,have sufficient tumor content at both timepoints to estimate changes in Pharmacodynamic biomarker percent area positive values.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 1 1 1 0 0 0 0
Mean (Standard Deviation)
Unit of Measure: percentage of cell
Baseline: Polyubiquitin Positive Index 0.99 [1]   (NA) 1.00 [1]   (NA) 0.99 [1]   (NA)
Change at C1D12: Polyubiquitin Positive Index -0.01 [1]   (NA) 0.00 [1]   (NA) 0.00 [1]   (NA)
Baseline: Ub-histone H2B Positive Index 0.953 [1]   (NA) 0.995 [1]   (NA) 0.990 [1]   (NA)
Change at C1D12: Ub-histone H2B Positive Index 0.018 [1]   (NA) 0.003 [1]   (NA) -0.003 [1]   (NA)
[1]
Standard deviation could not be calculated since only 1 participant was available for analysis.
18.Secondary Outcome
Title Percentage of Participants With Best Overall Response
Hide Description Best overall response for participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target and non target) must have reduction in short axis to less than (<) 10 millimeter (mm). Partial Response (PR): at least 30 percent (%) decrease in sum of diameter of target lesions, taking as reference baseline sum of diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum of diameter; PD: at least 20% increase in sum of diameter of target lesions, taking as reference, smallest sum on study (this includes baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame Baseline up to end of study (approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population included all participants who received at least 1 dose of TAK-243, have measurable disease at baseline, and have at least 1 post baseline disease assessment.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 3 4 2 3 2 5 1
Measure Type: Number
Unit of Measure: percentage of participants
CR 0 0 0 0 0 0 0
PR 33 0 0 0 0 0 0
SD 67 75 100 0 50 60 0
PD 0 25 0 100 50 40 100
19.Secondary Outcome
Title Duration of Response
Hide Description Duration of any response (CR or PR) was defined as the time (in both days and months) from the date of first documented response per the investigator response assessment to the date of first progressive disease after the first documented response or, if the participant discontinues treatment, the date of last disease assessment as per RECIST version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target and non target) must have reduction in short axis to <10 mm. PR: at least 30% decrease in sum of diameter of target lesions, taking as reference baseline sum of diameter.
Time Frame Baseline up to end of study (approximately 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable population where baseline and post-baseline assessments were available. The Response-evaluable population included all participants who received at least 1 dose of TAK-243, have measurable disease at baseline, and have at least 1 post baseline disease assessment.
Arm/Group Title Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description:
TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
Overall Number of Participants Analyzed 1 0 0 0 0 0 0
Median (Full Range)
Unit of Measure: months
6.24
(6.24 to 6.24)
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Cycle 10 Day 41) after the last dose of study drug
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-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Hide Arm/Group Description TAK-243 (MLN7243) 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped. TAK-243 (MLN7243) homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
All-Cause Mortality
Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      1/4 (25.00%)      2/4 (50.00%)      2/4 (50.00%)      1/5 (20.00%)      4/8 (50.00%)      0/1 (0.00%)    
Blood and lymphatic system disorders               
Anaemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Cardiac disorders               
Acute myocardial infarction  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Gastrointestinal disorders               
Duodenal and small intestinal stenosis and obstruction  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Small intestinal obstruction  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Flatulence, bloating and distension  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Abdominal distension  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Abdominal pain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Infections and infestations               
Pneumonia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Escherichia bacteraemia  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Viraemia and fungaemia not elsewhere classified (NEC)  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Sepsis  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Injury, poisoning and procedural complications               
Infusion related reaction  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Metabolism and nutrition disorders               
Dehydration  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Musculoskeletal and connective tissue disorders               
Back pain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Mesothelioma  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Non-small cell lung cancer  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Nervous system disorders               
Presyncope  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Breathing abnormalities  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  2/8 (25.00%)  0/1 (0.00%) 
Dyspnoea  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  2/8 (25.00%)  0/1 (0.00%) 
Respiratory failure  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Schedule A: TAK-243 1 mg Schedule A: TAK-243 2 mg Schedule A: TAK-243 4 mg Schedule A: TAK-243 8 mg Schedule A: TAK-243 12 mg Schedule A: TAK-243 18 mg Schedule A: TAK-243 Homozygous Mutant 4 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)      4/4 (100.00%)      4/4 (100.00%)      3/5 (60.00%)      8/8 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders               
Anaemia  1  0/3 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  1/4 (25.00%)  0/5 (0.00%)  4/8 (50.00%)  0/1 (0.00%) 
Leukopenia  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Lymphopenia  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Cardiac disorders               
Sinus bradycardia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Ear and labyrinth disorders               
Ear pain  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Gastrointestinal disorders               
Nausea  1  1/3 (33.33%)  3/4 (75.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  3/8 (37.50%)  0/1 (0.00%) 
Vomiting  1  0/3 (0.00%)  2/4 (50.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  4/8 (50.00%)  0/1 (0.00%) 
Diarrhoea  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Constipation  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  2/8 (25.00%)  0/1 (0.00%) 
Abdominal distension  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Abdominal pain  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Abdominal pain upper  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Proctalgia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Abdominal discomfort  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Gastrooesophageal reflux disease  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Stomatitis  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
General disorders               
Fatigue  1  1/3 (33.33%)  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  2/5 (40.00%)  1/8 (12.50%)  0/1 (0.00%) 
Asthenia  1  1/3 (33.33%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Non-cardiac chest pain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Chest pain  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Infusion site erythema  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Injection site erythema  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Medical device site bruise  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Medical device site phlebitis  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Oedema peripheral  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Pyrexia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Infections and infestations               
Urinary tract infection  1  1/3 (33.33%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Abscess oral  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Furuncle  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Sinusitis  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Upper respiratory tract infection  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Injury, poisoning and procedural complications               
Contusion  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Ligament sprain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Upper limb fracture  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Investigations               
Liver function test increased  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Blood alkaline phosphatase increased  1  1/3 (33.33%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Blood bilirubin increased  1  1/3 (33.33%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Alanine aminotransferase increased  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Amylase increased  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Aspartate aminotransferase increased  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Blood creatine phosphokinase increased  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Lipase increased  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Transaminases increased  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0 1/8 (12.50%)  0/1 (0.00%) 
Troponin T increased  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Hyperglycaemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  2/8 (25.00%)  0/1 (0.00%) 
Hyperlipasaemia  1  1/3 (33.33%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Hyponatraemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  1/1 (100.00%) 
Hypokalaemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Dehydration  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Hypoalbuminaemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Hypoglycaemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Hypomagnesaemia  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Hypophosphataemia  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/3 (0.00%)  2/4 (50.00%)  2/4 (50.00%)  1/4 (25.00%)  0/5 (0.00%)  2/8 (25.00%)  0/1 (0.00%) 
Back pain  1  0/3 (0.00%)  2/4 (50.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Pain in extremity  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Myalgia  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Musculoskeletal pain  1  0/3 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Muscle spasms  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Bone pain  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Flank pain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Muscular weakness  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Neck pain  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/8 (0.00%)  0/1 (0.00%) 
Pain in jaw  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Nervous system disorders               
Headache  1  1/3 (33.33%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Paraesthesia  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Aphasia  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Dizziness  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Neuropathy peripheral  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  1/1 (100.00%) 
Psychiatric disorders               
Anxiety  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Depression  1  1/3 (33.33%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Confusional state  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Irritability  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Renal and urinary disorders               
Acute kidney injury  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Haematuria  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Proteinuria  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Reproductive system and breast disorders               
Pelvic pain  1  0/3 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Dysphonia  1  0/3 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Dyspnoea  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Cough  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Dyspnoea exertional  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Oropharyngeal pain  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Pleural effusion  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Rhinitis allergic  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Rhinorrhoea  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Skin and subcutaneous tissue disorders               
Dermatitis acneiform  1  1/3 (33.33%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Skin fissures  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  0/8 (0.00%)  0/1 (0.00%) 
Vascular disorders               
Hypertension  1  0/3 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Embolism  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Hot flush  1  0/3 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/8 (12.50%)  0/1 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02045095    
Other Study ID Numbers: C33001
U1111-1203-6359 ( Other Identifier: WHO )
First Submitted: December 18, 2013
First Posted: January 24, 2014
Results First Submitted: November 6, 2017
Results First Posted: March 14, 2019
Last Update Posted: March 14, 2019