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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1181-0269 | Registry Identifier | WHO | |
| JapicCTI-163200 | Registry Identifier | JapicCTI |
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and maximum tolerated dose (MTD) of TAK-931 in participants with advanced nonhematologic tumors.
The drug being under investigation in this study is called TAK-931. The effect of TAK-931 is being evaluated in up to 100 participants who have nonhematologic (solid) neoplasms. This study will look at the safety, tolerability, and PK to determine the maximum tolerated dose (MTD) of TAK-931.
This multi-center trial will be conducted in Japan. The overall study duration is approximately 42 months for total of dose escalation cohorts and the safety expansion cohort. Participants will make multiple visits to the clinic with final visit approximately 30-40 days after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-931 | Experimental | TAK-931 30 mg, capsules, orally, QD or BID on Days 1-14 of each 21-day treatment cycle in dosing schedule A followed by dosing schedule B, C, D, E and F. In dosing schedules B through F, starting doses and dosing escalations will vary depending on the dosing data obtained from dosing in the previous schedule. Dose escalation of TAK-931 will be based on evaluation of clinical safety and tolerability and guided by accumulating PK data. 3-4 dose cohorts are expected for each dosing schedule. If the PK from the early cohorts support BID dosing, then study drug administration in subsequent cohorts may transition to a BID dosing schedule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-931 | Drug | TAK-931 oral capsules. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) Assessed by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Version 4.03 | Toxicity was evaluated by NCI CTCAE v4.03. DLT:any of following occurred events during Cycle 1 considered by investigator to be possibly related to therapy:1)Grade4 neutropenia,2)Febrile neutropenia lasting greater(>)1 hour,3)Grade greater than or equal to (>=)3 neutropenia with infection,4)Grade >=3 thrombocytopenia with bleeding,4)Grade 4 thrombocytopenia,5)delay in initiation of Cycle 2 by >14 days,6)Grade 2:<Grade 2 ejection fraction,7)other Grade 2 nonhematologic toxicities considered by investigator related to study drug and DLTs,8)who received <50 percent of doses of planned TAK-931 dosing in Cycle 1 for related AEs:<7 QD/<14 BID doses (Schedules A,B);<11 QD/<21 BID doses(Schedule D),<3 QD/<6 BID doses for(Schedule E),9)Grade >=3 nonhematologic toxicity except arthralgia/myalgia and fatigue, isolated >=Grade 3 laboratory abnormalities if it is asymptomatic and resolves to <=Grade 1 or baseline levels in <=7 days;inadequately treated Grade 3 nausea and/or vomiting and diarrhea. | Baseline up to Cycle 1 (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| Number of Participants With Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (up to Day 499) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration After First Dose of TAK-931 | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) | |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After First Dose of TAK-931 |
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Inclusion Criteria:
Histologically confirmed diagnosis of an advanced, nonhematologic/solid tumor (with the exception of primary brain tumor).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 .
For whom no effective standard therapy is available.
Life expectancy of greater than or equal to (>=3) months.
Female participants who:
Male participants, even if surgically sterilized (example, status postvasectomy), who:
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Ability to swallow oral medications, willingness to undergo serial skin punch biopsies, and suitable venous access for the study-required PK and pharmacodynamic sampling.
Clinical laboratory values as specified below within 28 days before the first dose of study drug:
Left ventricular ejection fraction (LVEF) greater than (>) 50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.
Recovered (that is, <=Grade 1 toxicity) from the reversible effects of prior anticancer therapy. Participants with ongoing toxicities at baseline may be eligible; however, any Grade 2 baseline toxicity (except for alopecia) should be discussed with the medical monitor.
Exclusion Criteria:
Who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.
Treatment with clinically significant enzyme inducers within 14 days before the first dose of study drug.
Treatment with any investigational products within 30 days before the first dose of study drug.
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 the first dose of study drug.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
History of any of the following within the last 3 months before administration of the first dose of study drug:
With any of the following blood pressure conditions:
Seizures requiring antiepileptic treatment.
History of uncontrolled brain metastasis unless:
Symptomatic and/or progressive central nervous system (CNS) metastases.
Ongoing medical conditions, such as acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before receiving the first dose of study drug.
Known history of human immunodeficiency virus (HIV) infection.
Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C (HCV) infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antibody can be enrolled but must have an undetectable hepatitis B viral load. Participants who have positive hepatitis C antibody must have an undetectable hepatitis C viral load.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption of study drug, such as total gastrectomy or GI conditions that could substantially modify gastric pH.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kashiwa | Chiba | Japan | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36970056 | Derived | Kuboki Y, Shimizu T, Yonemori K, Kojima T, Kondo S, Koganemaru S, Iwasa S, Harano K, Koyama T, Lu V, Zhou X, Niu H, Yanai T, Garcia-Ribas I, Doi T, Yamamoto N. Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study. Cancer Res Commun. 2022 Nov 14;2(11):1426-1435. doi: 10.1158/2767-9764.CRC-22-0277. eCollection 2022 Nov. | |
| 36338546 |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with advanced nonhematological solid tumors were enrolled to receive TAK-931 in 1 of the 4 treatment schedules: Schedule A, Schedule B, Schedule D and Schedule E. Schedules C and F were not conducted due to business reasons.
Participants took part in the study at 2 investigative sites in Japan from 24 March 2016 to 21 December 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Schedule A: TAK-931 30 mg | TAK-931 30 milligram (mg), capsule, orally, once daily (QD) for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG001 | Schedule A: TAK-931 40 mg | TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG002 | Schedule A: TAK-931 50 mg | TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG003 | Schedule A: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG004 | Schedule B: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily or twice daily (BID) for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG005 | Schedule B: TAK-931 80 mg | TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG006 | Schedule B: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG007 | Schedule B: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG008 | Schedule D: TAK-931 20 mg | TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG009 | Schedule D: TAK-931 30 mg | TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG010 | Schedule D: TAK-931 40 mg | TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG011 | Schedule E: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG012 | Schedule E: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| FG013 | Schedule E: TAK-931 150 mg | TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population was defined as all participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Schedule A: TAK-931 30 mg | TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG001 | Schedule A: TAK-931 40 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicities (DLTs) Assessed by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Version 4.03 | Toxicity was evaluated by NCI CTCAE v4.03. DLT:any of following occurred events during Cycle 1 considered by investigator to be possibly related to therapy:1)Grade4 neutropenia,2)Febrile neutropenia lasting greater(>)1 hour,3)Grade greater than or equal to (>=)3 neutropenia with infection,4)Grade >=3 thrombocytopenia with bleeding,4)Grade 4 thrombocytopenia,5)delay in initiation of Cycle 2 by >14 days,6)Grade 2:<Grade 2 ejection fraction,7)other Grade 2 nonhematologic toxicities considered by investigator related to study drug and DLTs,8)who received <50 percent of doses of planned TAK-931 dosing in Cycle 1 for related AEs:<7 QD/<14 BID doses (Schedules A,B);<11 QD/<21 BID doses(Schedule D),<3 QD/<6 BID doses for(Schedule E),9)Grade >=3 nonhematologic toxicity except arthralgia/myalgia and fatigue, isolated >=Grade 3 laboratory abnormalities if it is asymptomatic and resolves to <=Grade 1 or baseline levels in <=7 days;inadequately treated Grade 3 nausea and/or vomiting and diarrhea. | The DLT-evaluable population was defined as all participants who received at least 75% of their planned TAK-931 doses for their first cycle of treatment (unless interrupted by study drug-related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred. | Posted | Count of Participants | Participants | Baseline up to Cycle 1 (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
TEAEs are adverse events (AEs) that started after the first dose of study drug through 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (whichever occurred first) (up to Day 499)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Schedule A: TAK-931 30 mg | TAK-931 30 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oncologic complications and emergencies | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 15, 2020 | Dec 18, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Feb 23, 2018 | Dec 18, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| C000708995 | simurosertib |
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| Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After First Dose of TAK-931 | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| AUC12: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours After Multiple Doses of TAK-931 | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After First Dose of TAK-931 | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-931 | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Multiple Doses of TAK-931 | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After Multiple Doses of TAK-931 | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Multiple Doses of TAK-931 | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
| Schedule A, B and D: Change From Baseline in Phosphorylated Minichromosome Maintenance Complex-2 (pMCM2) (Ser40) Levels in Skin Based on Histological Score Nuclei (H-score) After Multiple Doses Of TAK-931 | H-score were a composite score that comprised of intensity and percentage of staining and were used for assessing amount of protein (in this case pMCM2 [Ser40]) present in a tissue sample. The composite score obtained by H-score is derived by adding of the percentages of cell staining at each intensity level multiplied by the weighted intensity of staining (0 [no staining], 1+ [weak staining], 2+ [medium staining], 3+ [strong staining]). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of pMCM2 (Ser40) in the tissue sample, while higher scores represent stronger expression of pMCM2 (Ser40) in the tissue samples. | Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days) |
| Schedule A, B and D: Change From Baseline in pMCM2 (Ser40) Levels in Skin Based on Positive Index After Multiple Doses Of TAK-931 | Positive index was calculated by taking the number of cells staining positive for the marker over the total number of cells. | Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days) |
| Overall Response Rate (ORR) | ORR was defined as percentage of participants who had achieved complete response (CR) and partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V 1.1). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD. | From date of first dose to the date of first documentation of progressive disease (PD) or death due to any cause, which ever occurred first (up to Month 45) |
| Progression-free Survival (PFS) | PFS was defined as the time from the date of first dose to the date of first documentation of PD or death due to any cause, whichever occurs first, as measured by RECIST V1.1. PD: 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. | From date of first dose to the date of first documentation of PD or death due to any cause, which ever occurred first (up to Month 45) |
| Duration of Response (DOR) | The DOR was defined as the time from the date of first documentation of a response (CR or PR) to the date of first documentation of PD, as measured by RECIST V 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: was at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD. PD: 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. DOR was analyzed using the Kaplan-Meier method. | From the date of first documentation of response to the date of first documentation of PD (up to Month 45) |
| Chuo-ku |
| Tokyo |
| Japan |
| Derived |
| Martin JC, Sims JR, Gupta A, Bakin AV, Ohm JE. WEE1 inhibition augments CDC7 (DDK) inhibitor-induced cell death in Ewing sarcoma by forcing premature mitotic entry and mitotic catastrophe. Cancer Res Commun. 2022 Jun;2(6):471-482. doi: 10.1158/2767-9764.crc-22-0130. Epub 2022 Jun 20. |
| Progressive Disease |
|
| Death |
|
| Lost to Follow-up |
|
TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG002 | Schedule A: TAK-931 50 mg | TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG003 | Schedule A: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG004 | Schedule B: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG005 | Schedule B: TAK-931 80 mg | TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG006 | Schedule B: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG007 | Schedule B: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG008 | Schedule D: TAK-931 20 mg | TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG009 | Schedule D: TAK-931 30 mg | TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG010 | Schedule D: TAK-931 40 mg | TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG011 | Schedule E: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG012 | Schedule E: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG013 | Schedule E: TAK-931 150 mg | TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. |
| BG014 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Body Surface Area (BSA) | Median | Standard Deviation | square meter (m˄2) |
|
|
|
|
| Primary | Number of Participants With Reporting One or More Treatment-emergent Adverse Events (TEAEs) | The safety population was defined as all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Baseline up to 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (up to Day 499) |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration After First Dose of TAK-931 | The pharmacokinetic (PK) population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After First Dose of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Median | Full Range | hours | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After First Dose of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | AUC12: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours After Multiple Doses of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After First Dose of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Multiple Doses of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Median | Full Range | hours | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours After Multiple Doses of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Multiple Doses of TAK-931 | The PK population was defined as all participants for whom there were sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameter(s). Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) |
|
|
|
| Secondary | Schedule A, B and D: Change From Baseline in Phosphorylated Minichromosome Maintenance Complex-2 (pMCM2) (Ser40) Levels in Skin Based on Histological Score Nuclei (H-score) After Multiple Doses Of TAK-931 | H-score were a composite score that comprised of intensity and percentage of staining and were used for assessing amount of protein (in this case pMCM2 [Ser40]) present in a tissue sample. The composite score obtained by H-score is derived by adding of the percentages of cell staining at each intensity level multiplied by the weighted intensity of staining (0 [no staining], 1+ [weak staining], 2+ [medium staining], 3+ [strong staining]). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of pMCM2 (Ser40) in the tissue sample, while higher scores represent stronger expression of pMCM2 (Ser40) in the tissue samples. | Pharmacodynamics population: all participants who received at least the first dose of TAK-931, had a baseline skin punch biopsy sample, and had at least 1 additional postbaseline skin punch biopsy sample. Overall number analyzed "N": participants who were evaluable for the outcome measure. Number analyzed "n": participants who were evaluable for this outcome measure for given categories. Data for this outcome measure was not collected and analyzed for Schedule E Cohorts due to business reasons. | Posted | Mean | Standard Deviation | score on a scale | Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days) |
|
|
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| Secondary | Schedule A, B and D: Change From Baseline in pMCM2 (Ser40) Levels in Skin Based on Positive Index After Multiple Doses Of TAK-931 | Positive index was calculated by taking the number of cells staining positive for the marker over the total number of cells. | Pharmacodynamics population: all participants who received at least the first dose of TAK-931, had a baseline skin punch biopsy sample, and had at least 1 additional postbaseline skin punch biopsy sample. Overall number analyzed "N": participants who were evaluable for the outcome measure. Number analyzed "n": participants who were evaluable for this outcome measure for given categories. Data for this outcome measure was not collected and analyzed for Schedule E Cohorts due to business reasons. | Posted | Mean | Standard Deviation | percentage of cell | Cycle 1 Day 1 pre-dose up to any dosing day after 3 consecutive days post-dose (up to Cycle 1 Day 8 [Schedule A and D]; Cycle 1 Day 7 [Schedule B]; Cycle 1 Day 12 [Schedule D]) (Cycle Length of Schedules A and D = 21 days; and Schedule B= 28 days) |
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| Secondary | Overall Response Rate (ORR) | ORR was defined as percentage of participants who had achieved complete response (CR) and partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V 1.1). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD. | The response-evaluable population is defined as participants who receive at least 1 dose of study drug, have measurable disease at baseline, and at least 1 post-baseline response assessment. Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Number | 95% Confidence Interval | percentage of participants | From date of first dose to the date of first documentation of progressive disease (PD) or death due to any cause, which ever occurred first (up to Month 45) |
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| Secondary | Progression-free Survival (PFS) | PFS was defined as the time from the date of first dose to the date of first documentation of PD or death due to any cause, whichever occurs first, as measured by RECIST V1.1. PD: 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. | The safety population was defined as all participants who received any amount of study drug. | Posted | Median | 95% Confidence Interval | months | From date of first dose to the date of first documentation of PD or death due to any cause, which ever occurred first (up to Month 45) |
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| Secondary | Duration of Response (DOR) | The DOR was defined as the time from the date of first documentation of a response (CR or PR) to the date of first documentation of PD, as measured by RECIST V 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: was at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD. PD: 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. DOR was analyzed using the Kaplan-Meier method. | The response-evaluable population is defined as participants who receive at least 1 dose of study drug, have measurable disease at baseline, and at least 1 post-baseline response assessment. Responders without documentation of PD were censored at the date of last response assessment that is stable disease or better. | Posted | Mean | Standard Deviation | months | From the date of first documentation of response to the date of first documentation of PD (up to Month 45) |
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|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Schedule A: TAK-931 40 mg | TAK-931 40 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG002 | Schedule A: TAK-931 50 mg | TAK-931 50 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 16 | 5 | 16 | 16 | 16 |
| EG003 | Schedule A: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily for 14 days in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG004 | Schedule B: TAK-931 60 mg | TAK-931 60 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG005 | Schedule B: TAK-931 80 mg | TAK-931 80 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 9 | 2 | 9 | 9 | 9 |
| EG006 | Schedule B: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG007 | Schedule B: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily or twice daily for 7 days, followed by 7 days of rest and repeated (7 days on and 7 days off treatment) in each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG008 | Schedule D: TAK-931 20 mg | TAK-931 20 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 6 | 1 | 6 | 5 | 6 |
| EG009 | Schedule D: TAK-931 30 mg | TAK-931 30 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG010 | Schedule D: TAK-931 40 mg | TAK-931 40 mg, capsule, orally, once daily in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 6 | 3 | 6 | 6 | 6 |
| EG011 | Schedule E: TAK-931 100 mg | TAK-931 100 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG012 | Schedule E: TAK-931 120 mg | TAK-931 120 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG013 | Schedule E: TAK-931 150 mg | TAK-931 150 mg, capsule, orally, once daily on Days 1 and 2 followed by 5 days of rest and repeated weekly (2 days on and 5 days off treatment) in each 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, death, or termination of the study by the sponsor. | 1 | 6 | 3 | 6 | 6 | 6 |
| Malignant ascites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Mediastinal neoplasms malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Thymoma malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Metastases to specified sites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Lymphangiosis carcinomatosa | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Pancreatic neoplasms malignant (excl islet cell and carcinoid) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Neutropenias 0 1 (33) 0 1 | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Gastrointestinal stenosis and obstruction NEC | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Duodenal and small intestinal stenosis and obstruction | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Duodenal obstruction | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Gastrointestinal inflammatory disorders NEC | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Nausea and vomiting symptoms | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Sepsis, bacteraemia, viraemia and fungaemia NEC | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Abdominal and gastrointestinal infections | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Lower respiratory tract and lung infections | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Appetite disorders | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Central nervous system haemorrhages and cerebrovascular accidents | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Increased intracranial pressure disorders | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Seizures and seizure disorders NEC | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Lower respiratory tract inflammatory and immunologic conditions | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pneumothorax and pleural effusions NEC | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Asthenic conditions | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Urinary abnormalities | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Malaise | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Application site pruritus | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Brain natriuretic peptide increased | Investigations | MedDRA (22.0) | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Jugular vein thrombosis | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (22.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Abnormal sensation in eye | Eye disorders | MedDRA (22.0) | Systematic Assessment |
|
| Alopecia areata | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Angular cheilitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Bronchitis bacterial | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (22.0) | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Dementia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dermatitis bullous | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (22.0) | Systematic Assessment |
|
| Duodenal obstruction | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypertonic bladder | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Infusion site extravasation | General disorders | MedDRA (22.0) | Systematic Assessment |
|
| Large intestinal haemorrhage | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
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| Lymphoedema | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
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| Miliaria | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA (22.0) | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Periodontitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Phlebitis | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
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| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Stress cardiomyopathy | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Tooth loss | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
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| Vagus nerve disorder | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Venous thrombosis | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA (22.0) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
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| Weight increased | Investigations | MedDRA (22.0) | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
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| Schedule B: Change at Cycle 1 Day 7 |
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| Schedule A and D: Change at Cycle 1 Day 8 |
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| Schedule D: Change at Cycle 1 Day 12 |
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| Schedule B: Change at Cycle 1 Day 7 |
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| Schedule A and D: Change at Cycle 1 Day 8 |
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| Schedule D: Change at Cycle 1 Day 12 |
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