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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1186-6838 | Registry Identifier | WHO |
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Termination of the study by the sponsor due to business decision.
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The purpose of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 when administered in East Asian participants with NHL who do not have an effective standard treatment available and to characterize the plasma and urine pharmacokinetic (PK) of TAK-659 in East Asian participants with NHL.
The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat people who have NHL or people who have relapsed and/or refractory NHL. This study will assess the safety, tolerability, PK, and preliminary efficacy of single-agent TAK-659 in East Asian participants with NHL.
The study will enroll approximately 33 to 47 participants, including at least 6 Japanese at RP2D dose level. Participants will be assigned to one of the following treatment groups:
Dose Escalation Part: TAK-659 Expansion Part: TAK-659 RP2D
This multi-center trial will be conducted in Japan and Republic of Korea. The maximum duration of participation in dose escalation part of the study is up to 12 months, unless in the opinion of the investigator and sponsor the participant would derive benefit from continued therapy beyond 12 months. In expansion part, participants who stop treatment for any other reason other than PD will continue to have PFS follow-up at the site every 2 months from the last dose of study drug up to 6 months or until PD. Participants will be followed 28 days after last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurs first, for a follow up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation Part Schedule A: TAK-659 60 mg in Cohort 1 | Experimental | TAK-659, tablet, orally, once daily, in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 60 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema . If 60 mg, once daily is safe and tolerable, then the dose will be escalated to 80 mg, once daily and subsequently in 20 mg increments until MTD and/or RP2D is determined. Based on emerging safety, tolerability, PK data, a lower dose will be permitted. |
|
| Dose Escalation Part Schedule B: TAK-659 80 mg in Cohort 1 | Experimental | TAK-659, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity, with a starting dose of 80 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. An alternative intermittent regimen may be evaluated if deemed necessary per the emerging data. |
|
| Expansion Part: TAK-659 MTD/RP2D | Experimental | TAK-659, tablet, orally, once daily, in a 28-day treatment cycle until disease progression or unacceptable toxicity in participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL) who are relapsed and/or refractory. Dose and dosing schedule for this part will be MTD/RP2D determined from results of dose escalation part. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-659 | Drug | TAK-659 Tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) | |
| Percentage of Participants With Grade 3 or Higher TEAEs | TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]). | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
| Percentage of Participants With Serious TEAEs | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) | |
| Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 | DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (<=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (>=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to <=Grade 1 or baseline for more than 7 days; >=Grade 3 thrombocytopenia with clinically significant bleeding; Grade >=3 nonhematologic toxicity except for treated >=Grade 3 nausea and/or emesis and diarrhea resolved to less than (<) Grade 3 within 3 days, Grade 3 fatigue <=72 hours, isolated asymptomatic >=Grade 3 laboratory abnormalities resolved to <=Grade 1 or baseline in <=7 days;received <75% of planned doses of study drug in Cycle 1;TAK-659-related >=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy. |
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Inclusion Criteria:
To be enrolled to the dose escalation part, participants must have histologically or cytologically confirmed diagnosis of NHL for which no effective standard treatment is available.
To be enrolled in the expansion part, participants must meet the following criteria:
Measurable disease per IWG 2007 criteria.
Eastern Cooperative Oncology Group performance status score of 0 or 1.
Life expectancy of longer than 3 months.
Adequate organ function, including the following:
Exclusion Criteria:
Received medications, supplements, or food/beverages that are P-glycoprotein (P-gp) inhibitors or inducers or strong cytochrome P450 (CYP) 3A inhibitors or inducers within a certain time frame prior to the first dose of study drug. Depending on the substance, the washout period for P-gp inhibitors or inducers or strong CYP3A inhibitors or inducers will be either 7 days or 5 times the half-life (half-life is related to the time required for elimination from the body). The washout period for grapefruit containing food or beverages is 5 days.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NHO Nagoya Medical Center | Nagoya | Aichi-ken | 460-0001 | Japan | ||
| National Cancer Center Hospital |
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 non-Hodgkin lymphoma (NHL) were enrolled in 1 of the 2 treatment schedules in the Dose Escalation Part to receive TAK-659: Dosing Schedule A and Dosing Schedule B. Dose Expansion part was not initiated and the data for secondary outcome measures was not analyzed due to early termination of the study by the sponsor due to business decision.
Participants took part in the study at 5 investigative sites in Japan and South Korea from 1 August 2017 to 17 August 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg | TAK-659 40 milligram (mg), tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| FG001 | Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg | TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| FG002 | Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| FG003 | Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| FG004 | Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg | TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety analysis set included participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg | TAK-659 40 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| BG001 | Dose Escalation Part, Dosing Schedule A: TAK-659 60 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 | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | The safety analysis set included participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
|
Treatment-emergent adverse events were adverse events that started from first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
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 | Dose Escalation Part, Dosing Schedule A: TAK-659 40 mg | TAK-659 40 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diverticulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 6, 2018 | Aug 17, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 20, 2020 | Aug 17, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000620859 | TAK-659 |
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| Cycle 1 (Cycle length =28 days) |
| Percentage of Participants Who Discontinued Study Drug Due to TEAEs | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
| Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A) | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A) | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A) | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
| Chuo-ku |
| Tokyo |
| 104-0045 |
| Japan |
| Seoul National University Hospital | Seoul | 3080 | South Korea |
| Samsung Medical Center | Seoul | 6315 | South Korea |
| Progressive Disease |
|
| Withdrawal by Subject |
|
| Adverse Event |
|
TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| BG002 | Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| BG003 | Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| BG004 | Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg | TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG002 | Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| OG003 | Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
| OG004 | Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg | TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. |
|
|
| Primary | Percentage of Participants With Grade 3 or Higher TEAEs | TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]). | The safety analysis set included participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
|
|
|
| Primary | Percentage of Participants With Serious TEAEs | The safety analysis set included participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
|
|
|
| Primary | Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 | DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (<=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (>=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to <=Grade 1 or baseline for more than 7 days; >=Grade 3 thrombocytopenia with clinically significant bleeding; Grade >=3 nonhematologic toxicity except for treated >=Grade 3 nausea and/or emesis and diarrhea resolved to less than (<) Grade 3 within 3 days, Grade 3 fatigue <=72 hours, isolated asymptomatic >=Grade 3 laboratory abnormalities resolved to <=Grade 1 or baseline in <=7 days;received <75% of planned doses of study drug in Cycle 1;TAK-659-related >=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy. | DLT-evaluable analysis set included participants who met the minimum treatment and safety evaluation requirements of the study or who experienced a DLT during Cycle 1. As planned, this outcome measure was analyzed and reported for dose escalation part only. | Posted | Number | percentage of participants | Cycle 1 (Cycle length =28 days) |
|
|
|
| Primary | Percentage of Participants Who Discontinued Study Drug Due to TEAEs | The safety analysis set included participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days) |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1 | The pharmacokinetic (PK) analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A) | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1 | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. | Posted | Median | Full Range | hours | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A) | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1 | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A) | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
|
|
|
| Primary | CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15 | The PK analysis set included participants who had sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure. CLR data was planned to be collected and analyzed for both of the Dosing Schedule A and B arms. However, urine sample was not collected in Dosing Schedule B due to administrative reasons. Therefore, data was not analyzed and reported for schedule B arm. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Dose Escalation Part, Dosing Schedule A: TAK-659 60 mg | TAK-659 60 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. | 0 | 6 | 6 | 6 | 6 | 6 |
| EG002 | Dose Escalation Part, Dosing Schedule A: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. | 0 | 4 | 3 | 4 | 4 | 4 |
| EG003 | Dose Escalation Part, Dosing Schedule B: TAK-659 80 mg | TAK-659 80 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Dose Escalation Part, Dosing Schedule B: TAK-659 100 mg | TAK-659 100 mg, tablet, orally, once daily as 7 days on and 7 days off treatment (dosing on 7 days followed by 7 days of rest) in each 28-days treatment cycle until disease progression, unacceptable toxicity, or withdrawal due to other reasons. | 0 | 1 | 1 | 1 | 1 | 1 |
| Herpes zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Large intestine infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Meningitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Jejunal perforation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| CD4 lymphocytes decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypophagia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Eyelid ptosis | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
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.
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |