A Safety and Pharmacokinetic Study of TAK-228 in Combinat... | NCT01899053 | Trialant
NCT01899053
Sponsor
Millennium Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Oct 30, 2019Actual
Enrollment
101Actual
Phase
Phase 1
Conditions
Advanced Nonhematologic Malignancies
Interventions
TAK-228
TAK-117
Countries
United States
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01899053
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
C32001
Secondary IDs
ID
Type
Description
Link
2013-000466-11
EudraCT Number
Brief Title
A Safety and Pharmacokinetic Study of TAK-228 in Combination With TAK-117 in Adult Participants With Advanced Nonhematologic Malignancies
Official Title
A Multicenter, Open-label, Phase 1b Study of MLN0128 (an Oral mTORC1/2 Inhibitor) in Combination With MLN1117 (an Oral PI3Kα Inhibitor) in Adult Patients With Advanced Nonhematologic Malignancies
Acronym
Not provided
Organization
TakedaINDUSTRY
Status Module
Record Verification Date
Oct 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 28, 2013Actual
Primary Completion Date
Jan 31, 2017Actual
Completion Date
Apr 30, 2018Actual
First Submitted Date
Jul 10, 2013
First Submission Date that Met QC Criteria
Jul 12, 2013
First Posted Date
Jul 15, 2013Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 26, 2019
Results First Submitted that Met QC Criteria
Oct 7, 2019
Results First Posted Date
Oct 30, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 7, 2019
Last Update Posted Date
Oct 30, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Millennium Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to evaluate the safety and to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), and dosing schedules of oral TAK-228+TAK-117. It also evaluated the single- and multiple-dose plasma pharmacokinetics (PK) of TAK-228+TAK-117 in participants with advanced nonhematologic malignancies.
Detailed Description
The drug being tested in this study was TAK-228. TAK-228 was tested to evaluate the safety, pharmacokinetics and efficacy, of TAK-228 in combination with TAK-117 when administered to adult participants with advanced nonhematologic malignancies.
The study enrolled 101 patients. The study consisted of 2 phases: an escalation stage followed by an expansion stage. Participants in escalation stage were assigned to the following treatment arms:
Dose escalation treatment arm A: TAK-228 2 or 4 mg capsule
Dose escalation treatment arm B: TAK-228 3, 4, 6 or 8 mg capsule
Dose escalation treatment arm C: TAK-228 3 mg capsule
Upon completion of the escalation stage, 1 combination treatment regimen was selected for further safety, tolerability, pharmacokinetics, and mutual drug-drug interaction characterization in the expansion stage. During treatment, participants in both stages received TAK-228 and TAK-117 capsules at prespecified doses in repeated 28-day cycles.
This multi-center trial conducted in the United States, United Kingdom and Spain. The overall time to participate in this study was approximately 68 weeks. Participants made multiple visits to the clinic, and a final visit after 30 days after last dose of study drug.
Conditions Module
Conditions
Advanced Nonhematologic Malignancies
Keywords
Drug Therapy
TAK-228
TAK-117
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
101Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Dose Escalation Treatment Arm A
Experimental
TAK-228 2 or 4 mg, capsule (milled or unmilled), orally, once daily every day (QD), and TAK-117 100, 200 or 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
Drug: TAK-228
Drug: TAK-117
Dose Escalation Treatment Arm B
Experimental
TAK-228 3, 4, 6 or 8 mg, capsule (milled or unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 or 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to approximately 38.7 weeks.
Drug: TAK-228
Drug: TAK-117
Dose Escalation Treatment Arm C
Experimental
TAK-228 3 mg, capsule (milled or unmilled), orally, once on MTuW QW, and TAK-117 300 or 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to approximately 64.3 weeks.
Drug: TAK-228
Drug: TAK-117
Drug-Drug Interaction (DDI) Expansion Cohort
Experimental
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Drug: TAK-228
Interventions
Name
Type
Description
Arm Group Labels
Other Names
TAK-228
Drug
TAK-228 Capsules
Dose Escalation Treatment Arm A
Dose Escalation Treatment Arm B
Dose Escalation Treatment Arm C
Drug-Drug Interaction (DDI) Expansion Cohort
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants Who Experienced at Least One or More Treatment-Emergent Adverse Event (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above-mentioned criteria.
From Baseline to 30 days after the last dose of study drug (Up to approximately 68 weeks)
Tmax: Time to Reach the Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Cmax: Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Terminal Phase Elimination Half-life (T1/2) After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Secondary Outcomes
Measure
Description
Time Frame
Objective Response Rate (ORR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female participants 18 years or older
Participants must have a diagnosis and documented disease progression of a solid tumor malignancy, excluding primary brain tumor, for which standard, curative, or life prolonging treatment does not exist or is no longer effective
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Female participants who are postmenopausal for at least 1 year prior to screening. For women of child-bearing potential agree to practice 2 effective methods of contraception or agree to practice true abstinence
Male participants must agree to practice effective barrier contraception during the entire study treatment period and through 30 days after last dose of study drug or practice true abstinence
Voluntary written consent
Suitable venous access
Participants must have a block of banked tumor tissue and/or fresh tumor tissue or at least 10 unstained slides available to be sent to the central laboratory
Clinical laboratory values as specified in the protocol
Participants must have radiographically or clinically evaluable tumor
Exclusion Criteria:
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
Treatment with any investigational products within 30 days before the first dose of study drug
Previous treatment with TAK-117 and/or TAK-228; previous treatment with dual mTORC1/2 or dual PI3K-mTOR inhibitors
Failed to have recovered from the reversible effects of previous anticancer therapies
Have received systemic corticosteroid (inhalers are allowed) within 7 days before the first administration of study drug
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drug
Diagnosis of diabetes mellitus
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection
Known human immunodeficiency virus (HIV) infection
Cardiovascular conditions as defined in the protocol
A requirement for positive inotropic support (excluding digoxin) or serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 1 year before screening
Participants who are taking proton pump inhibitors within 7 days of the first dose or who require treatment with proton pump inhibitors during the trial or those who are taking histamine-2 (H2) receptor antagonists within 24 hours of the first dose
Participants who received previous therapy with PI3K inhibitors or rapalogs will be allowed in the study if all other inclusion/exclusion criteria are met
Diagnosis of primary brain tumor or symptomatic brain metastasis. Participants with brain metastases must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Medical Monitor
Millennium Pharmaceuticals, Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Boston
Massachusetts
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Participants with a diagnosis of advanced nonhematologic malignancies were enrolled. A total of 101 participants were enrolled, out of which 81 entered the escalation phase, and 20 entered the expansion phase.
Recruitment Details
Participants took part in the study at 5 investigative sites in Spain, United Kingdom and United States from 28 June 2013 to 30 April 2018.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
FG001
Dose Escalation Treatment Arm A: Cohort 2A
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
SAP
No
Yes
No
Statistical Analysis Plan
Aug 18, 2016
Apr 26, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: TAK-117
MLN0128, INK128 or Sapanisertib
TAK-117
Drug
TAK-117 Capsules
Dose Escalation Treatment Arm A
Dose Escalation Treatment Arm B
Dose Escalation Treatment Arm C
Drug-Drug Interaction (DDI) Expansion Cohort
MLN1117
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
RAC: Accumulation Ratio for TAK-228 in the Dose Escalation Cohort
Accumulation ratio was based on AUC(0-24) between Cycle 1 Day 24 and Cycle 1 Day 1 (e.g. AUC(0-24) [Cycle 1 Day 24]/ AUC(0-24) [Cycle1 Day 1].
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Peak to Trough Ratio for TAK-228 After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Single-dose and Multiple-dose of TAK-117 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Cmax: Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-117 in the Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Terminal Phase Elimination Half-life (T1/2) After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
RAC: Accumulation Ratio for TAK-117 in the Dose Escalation Cohort
Accumulation ratio was based on AUC(0-24) between Cycle 1 Day 24 and Cycle 1 Day 1 (e.g. AUC(0-24) [Cycle 1 Day 24]/ AUC(0-24) [Cycle1 Day 1].
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Peak to Trough Ratio After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
Tmax: Time to Reach the Maximum Observed Plasma Concentration for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
Cmax: Maximum Observed Plasma Concentration for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
Terminal Phase Elimination Half-life (T1/2) for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
Peak to Trough Ratio for TAK-228 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
Tmax: Time to Reach the Maximum Observed Plasma Concentration for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
Cmax: Maximum Observed Plasma Concentration for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
Terminal Phase Elimination Half-life (T1/2) for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
Peak to Trough Ratio for TAK-117 in DDI Expansion Cohort
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
Baseline, Days 22 up to Day 28 of Cycle and every even-numbered cycle until disease progression or EOS (Up to approximately 68 weeks)
Duration of Response (DOR)
The DOR is defined as the time from the date of first documented response of CR/PR to the first documented progressive disease (PD), or censored at the last response assessment date that is SD or better for a participant that has not progressed. CR was defined as the disappearance of all target lesions and for non-target lesions, the disappearance of all non-target lesions and normalization of tumor marker level. PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions.
Baseline, Days 22 up to Day 28 of Cycle and every even-numbered cycle until disease progression or EOS (Up to approximately 68 weeks)
Nashville
Tennessee
United States
San Antonio
Texas
United States
Barcelona
Spain
Sutton
United Kingdom
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
FG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
FG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
FG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
FG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
FG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
FG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
FG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
FG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
FG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
FG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
FG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
FG0007 subjects
FG0013 subjects
FG0027 subjects
FG0033 subjects
FG0046 subjects
FG0053 subjects
FG0063 subjects
FG0073 subjects
FG0086 subjects
FG0093 subjects
FG01016 subjects
FG0117 subjects
FG01214 subjects
FG01320 subjects
COMPLETED
Completed=Participants who completed the study treatment.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
NOT COMPLETED
FG0007 subjects
FG0013 subjects
FG0027 subjects
FG0033 subjects
FG0046 subjects
FG0053 subjects
FG0063 subjects
FG0073 subjects
FG0086 subjects
FG0093 subjects
FG01016 subjects
FG0117 subjects
FG01214 subjects
FG01320 subjects
Type
Comment
Reasons
Progressive Disease
FG0004 subjects
FG0010 subjects
FG0023 subjects
FG0030 subjects
FG0043 subjects
FG0051 subjects
FG0061 subjects
FG0071 subjects
FG0084 subjects
FG0093 subjects
FG01012 subjects
FG0115 subjects
FG0128 subjects
FG01317 subjects
Adverse Event
FG0001 subjects
FG0011 subjects
FG0021 subjects
FG0033 subjects
FG004
Reason Not Specified
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Unsatisfactory Therapeutic Response
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Symptomatic Deterioration
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Safety population consisted of all enrolled participants who received at least 1 dose of any study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
BG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
BG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
BG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
BG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
BG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
BG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
BG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
BG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
BG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
BG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
BG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
BG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
BG014
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0007
BG0013
BG0027
BG0033
BG0046
BG0053
BG0063
BG0073
BG0086
BG0093
BG01016
BG0117
BG01214
BG01320
BG014101
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00059.9± 6.31
BG00169.3± 5.13
BG00250.6± 14.05
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0007
BG0012
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
White
BG0007
BG0012
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
United Kingdom
Title
Measurements
BG0000
BG0010
BG002
Height
Mean
Standard Deviation
cm
Title
Denominators
Categories
Title
Measurements
BG000164.0± 3.84
BG001165.1± 5.08
BG002
Weight
Mean
Standard Deviation
kg
Title
Denominators
Categories
Title
Measurements
BG00063.8± 9.11
BG00178.4± 1.34
BG002
Body Mass Index (BMI)
BMI was calculated as weight/[height^2].
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00023.7± 2.80
BG00128.8± 2.09
BG002
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 Who Experienced at Least One or More Treatment-Emergent Adverse Event (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above-mentioned criteria.
Safety population consisted of all enrolled participants who received at least 1 dose of any study drug.
Posted
Count of Participants
Participants
From Baseline to 30 days after the last dose of study drug (Up to approximately 68 weeks)
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG003
Title
Denominators
Categories
AEs
Title
Measurements
OG0007
OG0013
OG0027
OG003
Primary
Tmax: Time to Reach the Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
Pharmacokinetic (PK) population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Median
Full Range
hour
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Cmax: Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ng*hr/mL
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Terminal Phase Elimination Half-life (T1/2) After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
hour
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
PK population consisted of all participants enrolled during the dose escalation and expansion stage of the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants who were evaluable at each category.
Posted
Mean
Standard Deviation
L/hour
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
Primary
RAC: Accumulation Ratio for TAK-228 in the Dose Escalation Cohort
Accumulation ratio was based on AUC(0-24) between Cycle 1 Day 24 and Cycle 1 Day 1 (e.g. AUC(0-24) [Cycle 1 Day 24]/ AUC(0-24) [Cycle1 Day 1].
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Overall number of participants analyzed is the number of participants with evaluable data at both Days 1 and 24.
Posted
Mean
Standard Deviation
ratio
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
Primary
Peak to Trough Ratio for TAK-228 After Single-dose and Multiple-dose of TAK-228 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ratio
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Single-dose and Multiple-dose of TAK-117 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Median
Full Range
hour
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Cmax: Maximum Observed Plasma Concentration After Single-dose and Multiple-dose of TAK-117 in the Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ng*hr/mL
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Terminal Phase Elimination Half-life (T1/2) After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
hour
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
L/hr
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
RAC: Accumulation Ratio for TAK-117 in the Dose Escalation Cohort
Accumulation ratio was based on AUC(0-24) between Cycle 1 Day 24 and Cycle 1 Day 1 (e.g. AUC(0-24) [Cycle 1 Day 24]/ AUC(0-24) [Cycle1 Day 1].
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Overall number of participants analyzed is the number of participants with evaluable data at both Days 1 and 24.
Posted
Mean
Standard Deviation
ratio
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
Primary
Peak to Trough Ratio After Single-dose and Multiple-dose of TAK-117 in Dose Escalation Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ratio
Cycle 1: Days 1 and 24 predose and at multiple timepoints (up to 24 hours) postdose
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
Primary
Tmax: Time to Reach the Maximum Observed Plasma Concentration for TAK-228 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Median
Full Range
hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-228 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration for TAK-228 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
ng*hr/mL
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Terminal Phase Elimination Half-life (T1/2) for TAK-228 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-228 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
L/hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Peak to Trough Ratio for TAK-228 in DDI Expansion Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ratio
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 10 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Tmax: Time to Reach the Maximum Observed Plasma Concentration for TAK-117 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Median
Full Range
hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-117 in DDI Expansion Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Observed Quantifiable Concentration for TAK-117 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
ng*hr/mL
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Terminal Phase Elimination Half-life (T1/2) for TAK-117 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-117 in DDI Expansion Cohort
PK population consisted of all participants enrolled in the study who received at least 1 dose of TAK-228 and TAK-117 and had sufficient concentration-time data to calculate 1 or more PK parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Posted
Mean
Standard Deviation
L/hour
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Primary
Peak to Trough Ratio for TAK-117 in DDI Expansion Cohort
PK DDI-evaluable population consisted of all participants from Expansion Phase with sufficient dosing and concentration-time PK data to reliably estimate PK parameters for statistical analyses of effect of TAK-228 on TAK-117 PK and effect of TAK-117 on TAK-228 PK. Number analyzed is number of participants with evaluable data at given time-point.
Posted
Mean
Standard Deviation
ratio
Cycle 1, Day 3 predose and at multiple timepoints (up to 8 hours) postdose; Cycle 1, Day 17 predose and at multiple timepoints (up to 24 hours) postdose
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG000
Secondary
Objective Response Rate (ORR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
Safety population consisted of all enrolled participants who received at least 1 dose of any study drug.
Posted
Number
percentage of participants
Baseline, Days 22 up to Day 28 of Cycle and every even-numbered cycle until disease progression or EOS (Up to approximately 68 weeks)
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
Secondary
Duration of Response (DOR)
The DOR is defined as the time from the date of first documented response of CR/PR to the first documented progressive disease (PD), or censored at the last response assessment date that is SD or better for a participant that has not progressed. CR was defined as the disappearance of all target lesions and for non-target lesions, the disappearance of all non-target lesions and normalization of tumor marker level. PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions.
Safety population consisted of all enrolled participants who received at least 1 dose of any study drug. Data for this outcome measure is reported for the participants with objective response available.
Posted
Median
Full Range
days
Baseline, Days 22 up to Day 28 of Cycle and every even-numbered cycle until disease progression or EOS (Up to approximately 68 weeks)
ID
Title
Description
OG000
Dose Escalation Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
OG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
Time Frame
Baseline up to 30 days after the last dose of study drug (Up to approximately 68 weeks)
Description
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
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 Treatment Arm A: Cohort 1A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 4 cycles (each cycle was 28 days), up to 16 weeks.
0
7
2
7
6
7
EG001
Dose Escalation Treatment Arm A: Cohort 2A
TAK-228 4 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 100 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 3 cycles (each cycle was 28 days), up to 10.4 weeks.
0
3
0
3
3
3
EG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
1
7
1
7
7
7
EG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
0
3
1
3
3
3
EG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
1
6
1
6
5
6
EG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
0
3
0
3
3
3
EG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
0
3
1
3
3
3
EG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
0
3
1
3
3
3
EG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
0
6
1
6
6
6
EG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
0
3
1
3
3
3
EG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
2
16
4
16
16
16
EG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
0
7
4
7
7
7
EG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
2
20
9
20
19
20
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG0030 affected3 at risk
EG0040 affected6 at risk
EG0050 affected3 at risk
EG0060 affected3 at risk
EG0070 affected3 at risk
EG0080 affected6 at risk
EG0090 affected3 at risk
EG0100 affected16 at risk
EG0110 affected7 at risk
EG0120 affected14 at risk
EG0131 affected20 at risk
Dysphagia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with DDI expansion cohort (milled) and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Intestinal perforation
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with dose escalation treatment arm A: cohort 4A and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
General physical health deterioration
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Asthenia
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Fatigue
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gait disturbance
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Bile duct obstruction
Hepatobiliary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Peritonitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pneumonia
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Sinusitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urosepsis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Transaminases increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Endometrial cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with dose escalation treatment arm A: cohort 5B (milled) and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with DDI expansion cohort (milled) and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Salivary gland cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with dose escalation treatment arm A: cohort 5B (milled) and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Tumour fistulisation
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Nerve compression
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
One treatment-emergent death occurred during treatment with dose escalation treatment arm A: cohort 3A and is not related.
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Embolism
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG0030 affected3 at risk
EG0041 affected6 at risk
EG0051 affected3 at risk
EG0060 affected3 at risk
EG0070 affected3 at risk
EG0082 affected6 at risk
EG0090 affected3 at risk
EG0102 affected16 at risk
EG0110 affected7 at risk
EG0123 affected14 at risk
EG0132 affected20 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Palpitations
Cardiac disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Cataract
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0003 affected7 at risk
EG0012 affected3 at risk
EG0026 affected7 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected3 at risk
EG0025 affected7 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0003 affected7 at risk
EG0012 affected3 at risk
EG0023 affected7 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected3 at risk
EG0022 affected7 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected3 at risk
EG0023 affected7 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0022 affected7 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0022 affected7 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0021 affected7 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected3 at risk
EG0021 affected7 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Fatigue
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0003 affected7 at risk
EG0013 affected3 at risk
EG0023 affected7 at risk
EG003
Asthenia
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0011 affected3 at risk
EG0022 affected7 at risk
EG003
Oedema peripheral
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Chills
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0022 affected7 at risk
EG003
Pyrexia
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Pain
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Cystitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected3 at risk
EG0023 affected7 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected3 at risk
EG0022 affected7 at risk
EG003
Weight decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0011 affected3 at risk
EG0021 affected7 at risk
EG003
Transaminases increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood creatinine increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood glucose increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0003 affected7 at risk
EG0011 affected3 at risk
EG0022 affected7 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected3 at risk
EG0023 affected7 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0022 affected7 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dizziness
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0022 affected7 at risk
EG003
Headache
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Tremor
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Depression
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0003 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Paranasal sinus hypersecretion
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0002 affected7 at risk
EG0012 affected3 at risk
EG0022 affected7 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0022 affected7 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Pruritus generalised
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypertension
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Arteriosclerosis
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Sinus Tachycardia
Cardiac disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Atrial Septal Defect
Congenital, familial and genetic disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Deafness Transitory
Ear and labyrinth disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Ear Discomfort
Ear and labyrinth disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vision Blurred
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Visual Impairment
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dry Eye
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Diplopia
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Eye Oedema
Eye disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Abdominal Pain Lower
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Abdominal Tenderness
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Anal Incontinence
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Anorectal Discomfort
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Eructation
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gastrointestinal Disorder
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gastrointestinal Inflammation
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Tongue Oedema
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Gait Disturbance
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Non-Cardiac Chest Pain
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Chest Discomfort
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Early Satiety
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Face Oedema
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hernia Pain
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Infusion Site Extravasation
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Medical Device Site Pain
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Puncture Site Pain
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Temperature Intolerance
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Unevaluable Event
General disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Oral Herpes
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Oral Candidiasis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pneumonia
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Sinusitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Cellulitis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Ear Infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Fungal Infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hordeolum
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Puncture Site Infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Tooth Infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urinary Tract Infection Bacterial
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vulvovaginal Candidiasis
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Wound Infection
Infections and infestations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Gastrointestinal Disorder Postoperative
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Stoma Site Pain
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Skin Abrasion
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Post Procedural Complication
Injury, poisoning and procedural complications
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood Bilirubin Increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Electrocardiogram Qt Prolonged
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Platelet Count Decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood Albumin Decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood Cholesterol Increased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Blood Sodium Decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Haemoglobin Decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Neutrophil Count Decreased
Investigations
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Fistula
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Flank Pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Muscle Twitching
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Musculoskeletal Stiffness
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Neck Pain
Musculoskeletal and connective tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Diplegia
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Restless Legs Syndrome
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Speech Disorder
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Syncope
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vocal Cord Paralysis
Nervous system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Delirium
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Depressed Mood
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Libido Decreased
Psychiatric disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Acute Kidney Injury
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Bladder Spasm
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urinary Hesitation
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urinary Retention
Renal and urinary disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pelvic Pain
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Breast Oedema
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Breast Tenderness
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vulvovaginal Burning Sensation
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Vulvovaginal Discomfort
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vulvovaginal Pruritus
Reproductive system and breast disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dyspnoea Exertional
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Paranasal Sinus Discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Apnoea
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Bronchospasm
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Laryngeal Oedema
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Orthopnoea
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pneumonia Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Pulmonary Oedema
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Rhonchi
Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Dermatitis Acneiform
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Palmar-Plantar Erythrodysaesthesia Syndrome
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hypotension
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0021 affected7 at risk
EG003
Flushing
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Haematoma
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Hot Flush
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Orthostatic Hypotension
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Vena Cava Embolism
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Venous Thrombosis
Vascular disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Swelling Face
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Acne Cystic
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Decubitus Ulcer
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Leukoplakia
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Onychalgia
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Onychoclasis
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Pain Of Skin
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected3 at risk
EG0020 affected7 at risk
EG003
Rash Pruritic
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Skin Exfoliation
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Skin Lesion
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Skin Ulcer
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA version: 19.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected3 at risk
EG0020 affected7 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0007
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0045
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0116
ParticipantsOG01214
Title
Measurements
OG0001.000(0.50 to 4.00)
OG0011.000(0.97 to 1.03)
OG0021.000(0.50 to 4.07)
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0007
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0045
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0116
ParticipantsOG01214
Title
Measurements
OG00024.63± 7.355
OG00139.73± 7.853
OG00225.80± 8.188
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0007
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0045
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0116
ParticipantsOG01214
Title
Measurements
OG000120.888± 36.1184
OG001247.361± 156.0211
OG002138.929± 37.3727
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0005
ParticipantsOG0013
ParticipantsOG0025
ParticipantsOG0033
ParticipantsOG0044
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0071
ParticipantsOG0084
ParticipantsOG0092
ParticipantsOG01014
ParticipantsOG0116
ParticipantsOG0125
Title
Measurements
OG0005.090± 2.1653
OG0015.783± 3.3941
OG0026.214± 2.6649
OG003
Cycle 1, Day 24
ParticipantsOG0005
ParticipantsOG0012
ParticipantsOG0025
ParticipantsOG0030
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0005
ParticipantsOG0013
ParticipantsOG0025
ParticipantsOG0033
ParticipantsOG0044
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0071
ParticipantsOG0084
ParticipantsOG0092
ParticipantsOG01014
ParticipantsOG0116
ParticipantsOG0125
Title
Measurements
OG00016.534± 5.4762
OG00119.049± 11.8558
OG00214.419± 7.5636
OG003
Cycle 1, Day 24
ParticipantsOG0005
ParticipantsOG0012
ParticipantsOG0025
ParticipantsOG0030
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0003
OG0011
OG0024
OG0030
OG0043
OG0052
OG0062
OG0072
OG0082
OG0091
OG0108
OG0112
OG0126
Title
Denominators
Categories
Title
Measurements
OG0002.225± 1.4576
OG0011.25± 0
OG0021.495± 0.1884
OG0041.219± 0.3497
OG0051.569± 0.4099
OG0061.712± 0.2650
OG0071.718± 0.4329
OG0081.015± 0.1453
OG0091.58± 0
OG0101.172± 0.3363
OG0111.213± 0.1306
OG0121.461± 0.2246
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0004
ParticipantsOG0012
ParticipantsOG0025
ParticipantsOG0033
ParticipantsOG0044
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0072
ParticipantsOG0085
ParticipantsOG0092
ParticipantsOG01014
ParticipantsOG0114
ParticipantsOG0129
Title
Measurements
OG00016.546± 6.5659
OG00113.588± 8.3649
OG00214.553± 6.8807
OG003
Cycle 1, Day 24
ParticipantsOG0004
ParticipantsOG0011
ParticipantsOG0025
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0046
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0117
ParticipantsOG01214
Title
Measurements
OG0000.800(0.50 to 2.03)
OG0012.000(1.03 to 2.00)
OG0022.050(0.52 to 4.08)
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0046
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0117
ParticipantsOG01214
Title
Measurements
OG0001800.0± 1049.25
OG001988.7± 858.57
OG0023067.1± 1243.50
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG0027
ParticipantsOG0033
ParticipantsOG0046
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01016
ParticipantsOG0117
ParticipantsOG01214
Title
Measurements
OG00014586.139± 10434.5445
OG00111550.908± 11672.0852
OG00243948.190± 25421.3428
OG003
Cycle 1, Day 24
ParticipantsOG0006
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0006
ParticipantsOG0011
ParticipantsOG0020
ParticipantsOG0030
ParticipantsOG0040
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0072
ParticipantsOG0082
ParticipantsOG0090
ParticipantsOG0104
ParticipantsOG0113
ParticipantsOG0122
Title
Measurements
OG0006.590± 3.4673
OG0014.92± 0
OG0073.839± 3.5498
OG008
Cycle 1, Day 24
ParticipantsOG0004
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0030
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0006
ParticipantsOG0011
ParticipantsOG0020
ParticipantsOG0030
ParticipantsOG0040
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0072
ParticipantsOG0082
ParticipantsOG0090
ParticipantsOG0104
ParticipantsOG0113
ParticipantsOG0122
Title
Measurements
OG00016.993± 23.6496
OG0019.79± 0
OG007194.998± 258.2751
OG008
Cycle 1, Day 24
ParticipantsOG0004
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0030
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0004
OG0011
OG0025
OG0030
OG0045
OG0051
OG0062
OG0072
OG0083
OG0091
OG0109
OG0113
OG0129
Title
Denominators
Categories
Title
Measurements
OG0000.965± 0.1423
OG0011.33± 0
OG0021.161± 0.2506
OG0041.049± 0.9033
OG0051.18± 0
OG0062.007± 0.4766
OG0072.687± 0.5700
OG0081.748± 1.1575
OG0090.91± 0
OG0101.879± 1.5772
OG0110.925± 0.6281
OG0124.183± 5.8060
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
Title
Denominators
Categories
Cycle 1, Day 1
ParticipantsOG0005
ParticipantsOG0012
ParticipantsOG0026
ParticipantsOG0033
ParticipantsOG0046
ParticipantsOG0051
ParticipantsOG0063
ParticipantsOG0072
ParticipantsOG0086
ParticipantsOG0093
ParticipantsOG01013
ParticipantsOG0116
ParticipantsOG01213
Title
Measurements
OG00020.138± 21.6013
OG0018.845± 7.8516
OG0022.551± 0.9673
OG003
Cycle 1, Day 24
ParticipantsOG0005
ParticipantsOG0012
ParticipantsOG0025
ParticipantsOG0030
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00019
Title
Measurements
OG0001.000(0.38 to 4.08)
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00019
Title
Measurements
OG0000.983(0.42 to 2.02)
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00019
Title
Measurements
OG00060.02± 21.808
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00019
Title
Measurements
OG00071.99± 22.546
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00019
Title
Measurements
OG000301.613± 123.9584
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00019
Title
Measurements
OG000390.307± 155.3378
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00015
Title
Measurements
OG0006.823± 2.1608
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00016
Title
Measurements
OG0006.546± 1.8351
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00015
Title
Measurements
OG00015.368± 10.9714
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00016
Title
Measurements
OG00013.359± 11.3718
20
Title
Denominators
Categories
Cycle 1, Day 3, TAK-228 administered alone
ParticipantsOG00017
Title
Measurements
OG00022.982± 11.6286
Cycle 1, Day 10, TAK-228 administered with TAK-117
ParticipantsOG00018
Title
Measurements
OG00023.931± 15.6395
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG00019
Title
Measurements
OG0001.033(0.50 to 4.12)
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00019
Title
Measurements
OG0001.983(0.50 to 7.25)
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG00019
Title
Measurements
OG0005357.3± 2842.40
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00019
Title
Measurements
OG0005332.6± 2955.51
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG00019
Title
Measurements
OG00061148.949± 42799.7918
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00019
Title
Measurements
OG00063975.156± 53764.5716
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG0008
Title
Measurements
OG0006.420± 2.3635
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00011
Title
Measurements
OG0005.717± 2.3715
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG0008
Title
Measurements
OG00011.797± 18.0040
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00011
Title
Measurements
OG0009.134± 8.7741
20
Title
Denominators
Categories
Cycle 1, Day 10, TAK-117 administered with TAK-228
ParticipantsOG00017
Title
Measurements
OG0007.423± 7.423
Cycle 1, Day 17, TAK-117 administered alone
ParticipantsOG00018
Title
Measurements
OG00021.357± 44.3461
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.
Units
Counts
Participants
OG0007
OG0013
OG0027
OG0033
OG0046
OG0053
OG0063
OG0073
OG0086
OG0093
OG01016
OG0117
OG01214
OG01320
Title
Denominators
Categories
Title
Measurements
OG0000.0
OG0010.0
OG0020.0
OG0030.0
OG0040.0
OG0050.0
OG0060.0
OG0070.0
OG0080.0
OG0090.0
OG0100.0
OG0110.0
OG0120.0
OG01320.0
OG002
Dose Escalation Treatment Arm A: Cohort 3A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 5 cycles (each cycle was 28 days), up to 21.0 weeks.
OG003
Dose Escalation Treatment Arm A: Cohort 3A (Milled)
TAK-228 2 mg, capsule (milled), orally, once daily every day (QD), and TAK-117 200 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 2 cycles (each cycle was 28 days), up to 6.1 weeks.
OG004
Dose Escalation Treatment Arm A: Cohort 4A
TAK-228 2 mg, capsule (unmilled), orally, once daily every day (QD), and TAK-117 300 mg, capsule, orally, once on Monday, Wednesday and Friday each week (MWF QW) for up to 13 cycles (each cycle was 28 days), up to approximately 52 weeks.
OG005
Dose Escalation Treatment Arm B: Cohort 1B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 100 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 23.4 weeks.
OG006
Dose Escalation Treatment Arm B: Cohort 2B
TAK-228 3 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 6 cycles (each cycle was 28 days), up to 21.3 weeks.
OG007
Dose Escalation Treatment Arm B: Cohort 3B
TAK-228 6 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 5 cycles (each cycle was 28 days), up to 19.4 weeks.
OG008
Dose Escalation Treatment Arm B: Cohort 3B (Milled)
TAK-228 6 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 4 cycles (each cycle was 28 days), up to 15.4 weeks.
OG009
Dose Escalation Treatment Arm B: Cohort 4B
TAK-228 8 mg, capsule (unmilled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 2 cycles (each cycle was 28 days), up to 7.4 weeks.
OG010
Dose Escalation Treatment Arm B: Cohort 5B (Milled)
TAK-228 4 mg, capsule (milled), orally, once on Monday, Tuesday and Wednesday each week (MTuW QW), and TAK-117 200 mg, capsule, orally, once on MTuW QW for up to 9 cycles (each cycle was 28 days), up to 38.7 weeks.
OG011
Dose Escalation Treatment Arm C: Cohort 1C
TAK-228 3 mg, capsule (unmilled), orally, once on MTuW QW, and TAK-117 400 mg, capsule, orally, once on MTuW QW for up to 17 cycles (each cycle was 28 days), up to 64.3 weeks.
OG012
Dose Escalation Treatment Arm C: Cohort 2C (Milled)
TAK-228 3 mg, capsule (milled), orally, once on MTuW QW, and TAK-117 300 mg, capsule, orally, once on MTuW QW for up to 11 cycles (each cycle was 28 days), up to 43.4 weeks.
TAK-228 4 mg, capsule (milled), orally, once on MTuW QW except on Days 15, 16 and 17 of Cycle 1, and TAK-117 200 mg, capsule, orally, once on MTuW QW except on Days 1, 2 and 3 of Cycle 1 for up to 8 cycles (each cycle was 28 days), up to approximately 31.4 weeks.