A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02045095
Collaborator
(none)
29
7
7
33.3
4.1
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate safety and tolerability (establish maximum tolerated dose [MTD], inform the recommended phase 2 dose [RP2D], and identify the dose-limiting toxicities [DLTs]) of MLN7243.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a single arm Phase I study with multiple dosing cohorts as noted below:
-
Schedule A: MLN7243 1 mg
-
Schedule A: MLN7243 2 mg
-
Schedule A: MLN7243 4 mg
-
Schedule A: MLN7243 8 mg
-
Schedule A: MLN7243 12 mg
-
Schedule A: MLN7243 18 mg
-
Schedule A: MLN7243 Homozygous Mutant 4 mg
Study Design
Study Type:
Interventional
Actual Enrollment
:
29 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of MLN7243, an Inhibitor of Ubiquitin-Activating Enzyme (UAE), in Adult Patients With Advanced Solid Tumors
Actual Study Start Date
:
Jan 31, 2014
Actual Primary Completion Date
:
Nov 9, 2016
Actual Study Completion Date
:
Nov 9, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Schedule A: MLN7243 1 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 2 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 4 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 8 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 12 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 18 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
| Experimental: Schedule A: MLN7243 Homozygous Mutant 4 mg 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. |
Drug: MLN7243
Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)]
- Number of Participants With Laboratory Related TEAEs by System Organ Class (SOC) [Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)]
- Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT) [Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)]
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [Cycle 1 Day 1 up to Cycle 1 Day 11]
- Number of Participants With Clinically Significant Echocardiogram Abnormalities [Cycle 1 Day 2 up to 30 days after last dose of study drug (Cycle 10 Day 41)]
- Number of Participants With TEAEs Related to Tropinin I and T [Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)]
Secondary Outcome Measures
- Ceoi: Plasma Concentration at the End of Infusion for TAK-243 [Cycle 1 Day 1 and 11: pre-infusion to end of infusion (up to 10 minutes)]
- AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-243 [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]
- AUCτ: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-243 [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]
- AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-243 [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]
- CL: Total Clearance After Intravenous Administration for TAK-243 [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]
- Vss: Volume of Distribution at Steady State for TAK-243 [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]
- Aet: Amount of TAK-243 Excreted Unchanged in Urine [Cycle 1 Day 1; Cycle 1 Day 11]
- Fet: Percentage of TAK-243 Excreted Unchanged in Urine [Cycle 1 Day 1; Cycle 1 Day 11]
- Terminal Phase Elimination Half-life (T1/2) for TAK-243 [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]
- Change From Baseline in Immunohistochemistry (IHC) Biomarkers in Tumor Biopsies at Cycle 1 Day 12 (C1D12) as Assessed by Histological Score (H-score) [Baseline and Cycle 1 Day 12]
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.
- Change From Baseline in IHC Biomarkers in Tumor Biopsies at C1D12 as Assessed by Positive Index [Baseline and Cycle 1 Day 12]
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.
- Percentage of Participants With Best Overall Response [Baseline up to end of study (approximately 7 months)]
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.
- Duration of Response [Baseline up to end of study (approximately 7 months)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
-
Male or female participants 18 years or older.
-
Participants must have a histologically confirmed diagnosis of an advanced, metastatic malignant solid tumor and must have failed or exhausted standard therapies or for which no standard therapy is available.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-
Participants with adequate hematologic and organ function.
-
All participants must have radiographically detectable tumors with measurable disease as defined by RECIST (version 1.1).
-
Participants undergoing a biopsy procedure must have accessible lesions which are safe to biopsy.
-
Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy, except alopecia.
-
Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 4 months after the last dose of study drug, or agree to practice true abstinence.
Male participants who agree to practice effective barrier contraception during the entire study treatment period through 4 months after the last dose of study drug or agree to practice true abstinence.
- Suitable venous access for the study-required blood sampling including PK sampling.
Exclusion Criteria
Participants meeting any of the following exclusion criteria are not to be enrolled in the study:
-
Participants with clinically significant pre-existing cardiac impairment.
-
Participants homozygous for the ABCG2 (BCRP) c.421C greater than (>) 1 A polymorphism will be excluded from the study until the safety of a minimum of the first 3 dose levels has been characterized and the sponsor confirms that such participants can be enrolled at doses that are at least 3-fold lower than the most recently determined safe and tolerable dose among at least 3 dose limiting toxicities (DLT)-evaluable non-homozygous participants.
-
Participants with known active central nervous system (CNS) lesions are excluded. Systemic antineoplastic therapy or investigational agents within 21 days before the first dose of study drug.
-
Radiotherapy within 14 days before the first dose of study drug is not allowed except for limited field radiotherapy for palliative bone pain.
-
For participants where tumor biopsies are required or requested:
-
Any known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
-
Ongoing therapy with any anticoagulant or antiplatelet agents (example, aspirin, clopidogrel [Plavix®], heparin, or warfarin).
-
Major surgery within 28 days before the first dose of MLN7243.
-
Life-threatening illness unrelated to cancer.
-
Any evidence of active infection or antibiotic therapy within 14 days before the first dose of MLN7243.
-
Known human immunodeficiency virus (HIV) positivity or AIDS-related illness, hepatitis B virus, and hepatitis C virus.
-
Participants whose weight is less than (<) 40 kilogram (kg).
-
History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
-
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston | Massachusetts | United States | ||
| 2 | Saint Louis | Missouri | United States | ||
| 3 | Cleveland | Ohio | United States | ||
| 4 | Philadelphia | Pennsylvania | United States | ||
| 5 | Charleston | South Carolina | United States | ||
| 6 | Nashville | Tennessee | United States | ||
| 7 | San Antonio | Texas | United States |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02045095
Other Study ID Numbers:
- C33001
- U1111-1203-6359
First Posted:
Jan 24, 2014
Last Update Posted:
Mar 14, 2019
Last Verified:
Nov 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|---|---|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Schedule A: TAK-243 Total |
|---|---|
| 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 Participants | 29 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
56.8
(9.27)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
41.4%
|
| Male |
17
58.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
2
6.9%
|
| Not Hispanic or Latino |
22
75.9%
|
| Unknown or Not Reported |
5
17.2%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
5
17.2%
|
| White |
22
75.9%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
2
6.9%
|
| Region of Enrollment (Count of Participants) | |
| United States |
29
100%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [centimeter (cm)] |
170.88
(12.101)
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kilogram (kg)] |
79.69
(16.829)
|
| Body Surface Area (square meter (m^2)) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [square meter (m^2)] |
1.936
(0.2364)
|
Outcome Measures
| Title | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | |
| Time Frame | Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| TEAEs |
3
10.3%
|
4
NaN
|
4
NaN
|
4
NaN
|
4
NaN
|
8
NaN
|
1
NaN
|
| SAEs |
1
3.4%
|
1
NaN
|
2
NaN
|
2
NaN
|
1
NaN
|
4
NaN
|
0
NaN
|
| Title | Number of Participants With Laboratory Related TEAEs by System Organ Class (SOC) |
|---|---|
| Description | |
| Time Frame | Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Metabolism and nutrition disorders |
1
3.4%
|
1
NaN
|
1
NaN
|
3
NaN
|
1
NaN
|
4
NaN
|
1
NaN
|
| Blood and lymphatic system disorders |
1
3.4%
|
1
NaN
|
1
NaN
|
2
NaN
|
0
NaN
|
4
NaN
|
0
NaN
|
| Investigations |
1
3.4%
|
1
NaN
|
2
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
0
NaN
|
| Title | Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT) |
|---|---|
| Description | |
| Time Frame | Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Pyrexia |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
0
NaN
|
| Dyspnoea |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
2
NaN
|
0
NaN
|
| Dyspnoea exertional |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
0
NaN
|
| Hypertension |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
0
NaN
|
| Title | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 up to Cycle 1 Day 11 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Number [participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Clinically Significant Echocardiogram Abnormalities |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 2 up to 30 days after last dose of study drug (Cycle 10 Day 41) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Number [participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With TEAEs Related to Tropinin I and T |
|---|---|
| Description | |
| Time Frame | Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Number [participants] |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Ceoi: Plasma Concentration at the End of Infusion for TAK-243 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 and 11: pre-infusion to end of infusion (up to 10 minutes) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
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
(NA)
|
| Cycle 1 Day 11 |
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
(NA)
|
| Title | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
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 |
30.181
(12.8884)
|
50.337
(8.9494)
|
178.142
(NA)
|
228.053
(NA)
|
| Title | AUCτ: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
535.581
(NA)
|
377.812
(NA)
|
1132.160
(NA)
|
922.059
(192.1773)
|
|||
| Cycle 1 Day 11 |
506.693
(NA)
|
663.176
(261.1957)
|
771.491
(181.7875)
|
| Title | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
203.043
(10.0600)
|
375.541
(11.2872)
|
579.122
(201.1755)
|
768.728
(174.9927)
|
|||
| Cycle 1 Day 11 |
179.726
(NA)
|
509.785
(NA)
|
752.152
(NA)
|
864.533
(175.9351)
|
| Title | CL: Total Clearance After Intravenous Administration for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
19.724
(0.9773)
|
21.312
(0.6406)
|
22.749
(8.8967)
|
24.379
(5.6587)
|
|||
| Cycle 1 Day 11 |
22.162
(NA)
|
15.789
(NA)
|
16.194
(NA)
|
21.558
(4.8376)
|
| Title | Vss: Volume of Distribution at Steady State for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
29.806
(0.9494)
|
33.957
(5.8273)
|
37.596
(20.7520)
|
63.744
(39.5945)
|
|||
| Cycle 1 Day 11 |
34.120
(NA)
|
39.618
(NA)
|
56.573
(NA)
|
51.806
(18.8787)
|
| Title | Aet: Amount of TAK-243 Excreted Unchanged in Urine |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1; Cycle 1 Day 11 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Fet: Percentage of TAK-243 Excreted Unchanged in Urine |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1; Cycle 1 Day 11 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Terminal Phase Elimination Half-life (T1/2) for TAK-243 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 4 | 4 | 5 | 8 | 1 |
| Cycle 1 Day 1 |
7.001
(1.4372)
|
9.377
(4.6442)
|
5.765
(0.8607)
|
8.296
(4.3573)
|
|||
| Cycle 1 Day 11 |
5.572
(NA)
|
15.212
(NA)
|
27.446
(NA)
|
9.873
(6.3030)
|
| Title | Change From Baseline in Immunohistochemistry (IHC) Biomarkers in Tumor Biopsies at Cycle 1 Day 12 (C1D12) as Assessed by Histological Score (H-score) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Baseline: Polyubiquitin H-score |
286.00
(NA)
|
297.80
(NA)
|
282.00
(NA)
|
||||
| Change at C1D12: Polyubiquitin H-score |
-3.60
(NA)
|
-2.00
(NA)
|
4.20
(NA)
|
||||
| Baseline: Ub-histone H2B H-score |
269.750
(NA)
|
291.000
(NA)
|
290.750
(NA)
|
||||
| Change at C1D12: Ub-histone H2B H-score |
13.250
(NA)
|
3.250
(NA)
|
2.000
(NA)
|
| Title | Change From Baseline in IHC Biomarkers in Tumor Biopsies at C1D12 as Assessed by Positive Index |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Baseline: Polyubiquitin Positive Index |
0.99
(NA)
|
1.00
(NA)
|
0.99
(NA)
|
||||
| Change at C1D12: Polyubiquitin Positive Index |
-0.01
(NA)
|
0.00
(NA)
|
0.00
(NA)
|
||||
| Baseline: Ub-histone H2B Positive Index |
0.953
(NA)
|
0.995
(NA)
|
0.990
(NA)
|
||||
| Change at C1D12: Ub-histone H2B Positive Index |
0.018
(NA)
|
0.003
(NA)
|
-0.003
(NA)
|
| Title | Percentage of Participants With Best Overall Response |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 3 | 4 | 2 | 3 | 2 | 5 | 1 |
| CR |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| PR |
33
113.8%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| SD |
67
231%
|
75
NaN
|
100
NaN
|
0
NaN
|
50
NaN
|
60
NaN
|
0
NaN
|
| PD |
0
0%
|
25
NaN
|
0
NaN
|
100
NaN
|
50
NaN
|
40
NaN
|
100
NaN
|
| Title | Duration of Response |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Median (Full Range) [months] |
6.24
|
Adverse Events
| 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 | |||||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
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 (33.3%) | 1/4 (25%) | 2/4 (50%) | 2/4 (50%) | 1/5 (20%) | 4/8 (50%) | 0/1 (0%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Acute myocardial infarction | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Duodenal and small intestinal stenosis and obstruction | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Small intestinal obstruction | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Flatulence, bloating and distension | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Abdominal distension | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Abdominal pain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Pneumonia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Escherichia bacteraemia | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Viraemia and fungaemia not elsewhere classified (NEC) | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Sepsis | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Infusion related reaction | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Dehydration | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Back pain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Mesothelioma | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Non-small cell lung cancer | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Presyncope | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Breathing abnormalities | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/8 (25%) | 0/1 (0%) | |||||||
| Dyspnoea | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/8 (25%) | 0/1 (0%) | |||||||
| Respiratory failure | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
Other (Not Including 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 | 3/3 (100%) | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 3/5 (60%) | 8/8 (100%) | 1/1 (100%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/3 (0%) | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 0/5 (0%) | 4/8 (50%) | 0/1 (0%) | |||||||
| Leukopenia | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Lymphopenia | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Sinus bradycardia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Ear pain | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Nausea | 1/3 (33.3%) | 3/4 (75%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 3/8 (37.5%) | 0/1 (0%) | |||||||
| Vomiting | 0/3 (0%) | 2/4 (50%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 4/8 (50%) | 0/1 (0%) | |||||||
| Diarrhoea | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Constipation | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/8 (25%) | 0/1 (0%) | |||||||
| Abdominal distension | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Abdominal pain | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Abdominal pain upper | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Proctalgia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Abdominal discomfort | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Gastrooesophageal reflux disease | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Stomatitis | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 1/3 (33.3%) | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 2/5 (40%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Asthenia | 1/3 (33.3%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Non-cardiac chest pain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Chest pain | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Infusion site erythema | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Injection site erythema | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Medical device site bruise | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Medical device site phlebitis | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Oedema peripheral | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Pyrexia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Urinary tract infection | 1/3 (33.3%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Abscess oral | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Furuncle | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Sinusitis | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Upper respiratory tract infection | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Contusion | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Ligament sprain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Upper limb fracture | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Investigations | ||||||||||||||
| Liver function test increased | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Blood alkaline phosphatase increased | 1/3 (33.3%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Blood bilirubin increased | 1/3 (33.3%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Alanine aminotransferase increased | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Amylase increased | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Blood creatine phosphokinase increased | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Lipase increased | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Transaminases increased | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0 | 1/8 (12.5%) | 0 | 0/1 (0%) | 0 | ||||
| Troponin T increased | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Decreased appetite | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 2/4 (50%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Hyperglycaemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/8 (25%) | 0/1 (0%) | |||||||
| Hyperlipasaemia | 1/3 (33.3%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Hyponatraemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 1/1 (100%) | |||||||
| Hypokalaemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Dehydration | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Hypoalbuminaemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Hypoglycaemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Hypomagnesaemia | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Hypophosphataemia | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/3 (0%) | 2/4 (50%) | 2/4 (50%) | 1/4 (25%) | 0/5 (0%) | 2/8 (25%) | 0/1 (0%) | |||||||
| Back pain | 0/3 (0%) | 2/4 (50%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Pain in extremity | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Myalgia | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Musculoskeletal pain | 0/3 (0%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Muscle spasms | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Bone pain | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Flank pain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Muscular weakness | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Neck pain | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Pain in jaw | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Headache | 1/3 (33.3%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Paraesthesia | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Aphasia | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Dizziness | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Neuropathy peripheral | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 1/1 (100%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Anxiety | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Depression | 1/3 (33.3%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Confusional state | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Irritability | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Acute kidney injury | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Haematuria | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Proteinuria | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Pelvic pain | 0/3 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Dysphonia | 0/3 (0%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Dyspnoea | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Cough | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Dyspnoea exertional | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Oropharyngeal pain | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Pleural effusion | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Rhinitis allergic | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Rhinorrhoea | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dermatitis acneiform | 1/3 (33.3%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Skin fissures | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/8 (0%) | 0/1 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Hypertension | 0/3 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Embolism | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
| Hot flush | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/1 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02045095
Other Study ID Numbers:
- C33001
- U1111-1203-6359
First Posted:
Jan 24, 2014
Last Update Posted:
Mar 14, 2019
Last Verified:
Nov 1, 2018