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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1202-4296 | Registry Identifier | WHO | |
| 1066064639 | Registry Identifier | Taiwan Ministry of Health and Welfare | |
| 20170270241 | Other Identifier | Korea Food and Drug Administration | |
| JapicCTI-183822 | Registry Identifier | Japan Ministry of Health |
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More favorable safety profile was observed in QD schedule, therefore further enrollment in QW schedule was terminated.
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The purpose of this study is to evaluate the safety and tolerability, recommended phase 2 dose (RP2D), and to characterize PK of TAK-228 administered once daily or once weekly to East Asian participants with advanced nonhematological malignancies.
The drug being tested in this study is called TAK-228. TAK-228 is being tested to treat East Asian participants with advanced nonhematological malignancies for whom standard anticancer treatment is not available or is no longer effective. This study will assess the safety, tolerability, PK and will determine the RP2Ds of TAK-228.
The study will enroll approximately 46 participants, including at least 6 Japanese participants at RP2D dose level. Participants will be assigned to one of the following treatment arms:
This multi-center trial will be conducted in South Korea, Taiwan, and Japan. The overall time to participate in this 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. Participants will be followed for 30 days after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-228 Once Daily | Experimental | TAK-228, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity or withdrawal of consent with a starting dose of 2 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema. If 2 mg, once daily, is safe and tolerable, then the dose will be escalated to 4 mg, once daily, until RP2D is determined. |
|
| TAK-228 Once Weekly | Experimental | TAK-228, milled capsule, orally, once weekly, on an empty stomach in Cycle 1 of a 28-day treatment cycle and following a light meal from Cycle 2 for up to 12 months or until disease progression or unacceptable toxicity or withdrawal of consent with a starting dose of 20 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. If 20 mg, once weekly, is safe and tolerable, then the dose will be escalated to 30 mg, once weekly, until RP2D is determined. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-228 | Drug | TAK-228 Capsules. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) | |
| Number of Participants With Grade 3 or Higher TEAEs | Adverse event (AE) Grades were evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.03. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
| Number of Participants With Serious TEAEs | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) | |
| Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 | Toxicity was evaluated according to NCI CTCAE version 4.03. DLT was defined as any of the following occurred events within the first 28 days of the administration of TAK-228 that were considered by investigator to be possibly related to therapy: Grade >=3 nonhematologic toxicity except for inadequately treated Grade 3 nausea and/or vomiting and diarrhea, Grade 3 hyperglycemia lasting <=14 days, Grade 3 rash lasting <=3 days; Grade 3 thrombocytopenia with hemorrhage or requiring platelet transfusion; Grade 3 anemia requiring blood transfusion; Grade 4 neutropenia lasting >7 days; Grade >=3 neutropenia of any duration with fever >=38.5 degree celsius and/or systemic infection; Any other >=Grade 4 hematologic toxicity; Inability to administer at least 75 percent (%) of planned doses of TAK-228 within Cycle 1 due to treatment-related toxicity and any clinically significant occurrence that the investigators and sponsor agreed would place participants at an undue safety risk. | Baseline up to Day 28 in Cycle 1 (Cycle length= 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Benefit Rate (CBR) | The CBR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD). BOR was defined as the best response recorded after the first dose of study drug until subsequent therapy. As per Response Evaluation Criteria Solid Tumors (RECIST) version 1.1 guidelines, CR was defined as disappearance of all target lesions and non-target lesions, and normalization of tumor marker level. PR was defined as >= 30% decrease in the sum of the longest diameter (LD) of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD). PD was defined as at least a 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. |
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Inclusion Criteria:
With advanced nonhematologic malignancies, with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy. History of brain metastasis may be allowed if all of the following criteria are met:
Received not more than 4 prior lines of systemic cytotoxic chemotherapy for advanced or metastatic disease.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Screening clinical laboratory values as specified below:
Note: Prophylactic transfusions of blood products or any prophylactic use of hematopoietic growth factors (such as erythropoietin, thrombopoietin, granulocyte colony stimulating factor [G-CSF], and granulocyte macrophage colony stimulating factor [GM-CSF]) is not permitted during the screening period.
Hepatic: Total bilirubin less than or equal to (<=) 1.5*upper limit of normal (ULN), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <=2.5*ULN (<=5*ULN if their elevation can be reasonably ascribed to the presence of hepatocellular carcinoma, biliary tract cancer, or metastatic disease in liver).
Adequate renal function, defined as meeting any 1 of the following criteria:
Exclusion Criteria:
Diagnosis of primary brain tumor.
Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression.
Failed to recover from the reversible effects of prior anticancer therapies with the exception of alopecia, and after-effects associated with prior tyrosine kinase inhibitor therapy, such as hair depigmentation, hypothyroidism, and/or splinter hemorrhage.
Initiation of hematopoietic growth factors within 1 week before the first dose of study drug.
Manifestations of malabsorption caused by prior gastrointestinal surgery, gastrointestinal disease, or for some other reason that may alter the absorption of TAK-228. In addition, participants with enteric stomata are also excluded.
Poorly controlled diabetes mellitus defined as Hemoglobin A1c (HbA1c) greater than (>) 7%; participants with a history of transient glucose intolerance caused by corticosteroid administration are allowed if all other eligibility criteria are met.
Known human immunodeficiency virus infection.
Known hepatitis B surface antigen (HBsAg) positive, or known or suspected active hepatitis C virus (HCV) infection. Note: Participants who have isolated positive hepatitis B core antibody (HBcAb) and/or hepatitis B surface antibody (HBsAb) (that is, in the setting of negative HBsAg) may be enrolled but must have an undetectable hepatitis B virus (HBV) viral load. Participants who have positive hepatitis C virus antibody (HCVAb) may be enrolled but must have an undetectable HCV viral load.
Significant active cardiovascular or pulmonary disease before the first dose of study drug, including:
Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center Hospital East | Kashiwa-shi | Chiba | 277-8577 | Japan | ||
| National Cancer Center Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34843044 | Derived | Shimizu T, Kuboki Y, Lin CC, Yonemori K, Yanai T, Faller DV, Dobler L, Gupta N, Sedarati F, Kim KP. A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies. Target Oncol. 2022 Jan;17(1):15-24. doi: 10.1007/s11523-021-00855-w. Epub 2021 Nov 29. |
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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 malignancies were enrolled in Dose Escalation and Expansion Phase to receive TAK-228 in 1 of the 2 schedules: once daily (QD) or once weekly (QW). Further enrollment in QW schedule was stopped and study was terminated before QW expansion because more favorable safety profile were observed in QD schedule.
Participants took part in the study at 4 investigative sites in Japan, South Korea and Taiwan from 17 January 2018 to 28 August 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation, Daily Dosing Arm: TAK-228 2 mg | TAK-228 2 milligram (mg), milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| FG001 | Dose Escalation, Daily Dosing Arm: TAK-228 3 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Dose Escalation Phase |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 8, 2018 | Aug 20, 2020 |
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| Number of Participants With TEAEs Leading to Study Drug Discontinuation | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
| Cmax: Maximum Observed Plasma Concentration for TAK-228 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-228 on Cycle 1 Day 15 | Cycle 1 Day 15 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-228 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-228 on Cycle 1 Day 15 | Cycle 1 Day 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| Daily Dosing Arms, AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours for TAK-228 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) |
| Daily Dosing Arms, AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours for TAK-228 on Cycle 1 Day 15 | Cycle 1 Day 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
| Weekly Dosing Arms, AUC168: Area Under the Concentration-time Curve From 0 to 168 Hours for TAK-228 on Cycle 1 Day 1 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
| Weekly Dosing Arms, AUC168: Area Under the Concentration-time Curve From 0 to 168 Hours for TAK-228 on Cycle 1 Day 15 | Cycle 1 Day 15 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
| AUClast: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Measurable Concentration for TAK-228 on Cycle 1 Day 1 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
| AUClast: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Measurable Concentration for TAK-228 on Cycle 1 Day 15 | Cycle 1 Day 15 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
| AUC∞: Area Under the Plasma Concentration-time Curve From 0 to Infinity for TAK-228 on Cycle 1 Day 1 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
| Baseline Up to 1 Year 7 Months |
| Chūōku |
| Tokyo-To |
| 104-0045 |
| Japan |
| Asan Medical Center | Seoul | 05505 | South Korea |
| National Taiwan-University Hospital | Taipei | 100 | Taiwan |
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| FG002 | Dose Escalation, Daily Dosing Arm: TAK-228 4 mg | TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| FG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| FG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| FG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| COMPLETED |
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| NOT COMPLETED |
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| Dose Expansion Phase |
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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, Daily Dosing Arm: TAK-228 2 mg | TAK-228 2 milligram (mg), milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG001 | Dose Escalation, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG002 | Dose Escalation, Daily Dosing Arm: TAK-228 4 mg | TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | centimeter (cm) |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Smoking Classification | Count of Participants | Participants |
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| Asian Sub-Category | Count of Participants | Participants |
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| 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 Treatment Emergent Adverse Events (TEAEs) | The safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
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| Primary | Number of Participants With Grade 3 or Higher TEAEs | Adverse event (AE) Grades were evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.03. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. | The safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
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| Primary | Number of Participants With Serious TEAEs | The safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
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| Primary | Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1 | Toxicity was evaluated according to NCI CTCAE version 4.03. DLT was defined as any of the following occurred events within the first 28 days of the administration of TAK-228 that were considered by investigator to be possibly related to therapy: Grade >=3 nonhematologic toxicity except for inadequately treated Grade 3 nausea and/or vomiting and diarrhea, Grade 3 hyperglycemia lasting <=14 days, Grade 3 rash lasting <=3 days; Grade 3 thrombocytopenia with hemorrhage or requiring platelet transfusion; Grade 3 anemia requiring blood transfusion; Grade 4 neutropenia lasting >7 days; Grade >=3 neutropenia of any duration with fever >=38.5 degree celsius and/or systemic infection; Any other >=Grade 4 hematologic toxicity; Inability to administer at least 75 percent (%) of planned doses of TAK-228 within Cycle 1 due to treatment-related toxicity and any clinically significant occurrence that the investigators and sponsor agreed would place participants at an undue safety risk. | The DLT-evaluable set included participants who had received at least 75% of planned doses of TAK-228 in Cycle 1 unless interrupted by treatment-related events and had sufficient follow-up data considered by sponsor and investigator to determine whether DLT occurred.This outcome measure was planned to be assessed only in the dose escalation phase. | Posted | Count of Participants | Participants | Baseline up to Day 28 in Cycle 1 (Cycle length= 28 days) |
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| Primary | Number of Participants With TEAEs Leading to Study Drug Discontinuation | The safety analysis set included all participants who received at least 1 dose of the study drug. | Posted | Count of Participants | Participants | Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) |
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| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-228 on Cycle 1 Day 1 | The pharmacokinetic (PK) analysis set included participants with 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) |
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| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-228 on Cycle 1 Day 15 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 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 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
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| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-228 on Cycle 1 Day 1 | The PK analysis set included participants with 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) |
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| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-228 on Cycle 1 Day 15 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 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 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
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| Primary | Daily Dosing Arms, AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours for TAK-228 on Cycle 1 Day 1 | PK analysis set: Participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. This outcome measure was planned to be assessed only in Daily Dosing arms. 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*hour per milliliter (ng*hr/mL) | Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
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| Primary | Daily Dosing Arms, AUC24: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours for TAK-228 on Cycle 1 Day 15 | PK analysis set: Participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. This outcome measure was planned to be assessed only in Daily Dosing arms. 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*hr/mL | Cycle 1 Day 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) |
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| Primary | Weekly Dosing Arms, AUC168: Area Under the Concentration-time Curve From 0 to 168 Hours for TAK-228 on Cycle 1 Day 1 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. This outcome measure was planned to be assessed only in the Weekly Dosing arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
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| Primary | Weekly Dosing Arms, AUC168: Area Under the Concentration-time Curve From 0 to 168 Hours for TAK-228 on Cycle 1 Day 15 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. This outcome measure was planned to be assessed only in the Weekly Dosing arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 1 Day 15 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
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| Primary | AUClast: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Measurable Concentration for TAK-228 on Cycle 1 Day 1 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
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| Primary | AUClast: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Measurable Concentration for TAK-228 on Cycle 1 Day 15 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 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*hr/mL | Cycle 1 Day 15 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
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| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From 0 to Infinity for TAK-228 on Cycle 1 Day 1 | The PK analysis set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 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*hr/mL | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Clinical Benefit Rate (CBR) | The CBR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD). BOR was defined as the best response recorded after the first dose of study drug until subsequent therapy. As per Response Evaluation Criteria Solid Tumors (RECIST) version 1.1 guidelines, CR was defined as disappearance of all target lesions and non-target lesions, and normalization of tumor marker level. PR was defined as >= 30% decrease in the sum of the longest diameter (LD) of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD). PD was defined as at least a 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. | The safety set includes all participants who received at least 1 dose of study drug. | Posted | Number | Percentage of participants | Baseline Up to 1 Year 7 Months |
|
TEAEs are AEs that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Cycle 12 Day 58)
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, Daily Dosing Arm: TAK-228 2 mg | TAK-228 2 milligram (mg), milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG001 | Dose Escalation, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 6 | 2 | 6 | 6 | 6 |
| EG002 | Dose Escalation, Daily Dosing Arm: TAK-228 4 mg | TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 7 | 3 | 7 | 7 | 7 |
| EG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. | 0 | 3 | 1 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Genital Herpes | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cholangitis acute | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stomatitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Gastrointestinal inflammation | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash erythmatous | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increases | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood creatinine phosphokinase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Cystitis bacterial | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Large intestine infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Post herpetic neuralgia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cancer pain | 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 |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Angular cheilitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Laryngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Genital haemorrhage | Reproductive system and breast disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Eczema asteatotic | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Haemoglobin increased | Investigations | MedDRA (22.0) | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 28, 2019 | Aug 20, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| C572449 | sapanisertib |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Taiwan, Province Of China |
|
| Korea, Republic Of |
|
| Moderate Smoker (6-20 Cigarettes/ day) |
|
| Unknown |
|
| Korean |
|
| Chinese |
|
TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG001 | Dose Escalation, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG002 | Dose Escalation, Daily Dosing Arm: TAK-228 4 mg | TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG003 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| Dose Expansion, Daily Dosing Arm: TAK-228 3 mg |
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
|
|
| Dose Expansion, Daily Dosing Arm: TAK-228 3 mg |
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|
TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
| OG002 | Dose Escalation, Daily Dosing Arm: TAK-228 4 mg | TAK-228 4 mg, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG003 | Dose Expansion, Daily Dosing Arm: TAK-228 3 mg | TAK-228 3 mg, milled capsule, orally, once daily, on an empty stomach in each 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG004 | Dose Escalation, Weekly Dosing Arm: TAK-228 20 mg | TAK-228 20 mg, milled capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| OG005 | Dose Escalation, Weekly Dosing Arm: TAK-228 30 mg | TAK-228 30 mg milled, capsule, orally, once weekly, on an empty stomach in a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
|
|