Neoplasms, Advanced Solid
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet.
Detailed description
The drug being tested in this study is called TAK-931. TAK 931 is being tested to treat participants who have advanced solid tumors. This study will look at relative bioavailability, effect of food and gastric pH modification on the PK of TAK-931. The study will enroll approximately 44 participants. The study will be conducted in 2 parts: Part 1 and Part 2. In Part 1 and Part 2, participants will be randomly assigned (by chance, like flipping a coin) in a crossover design. In Part 1, participants will be assigned to 1 of the 2 following treatment sequences: * TAK-931 80 mg PIC + TAK-931 80 mg Tablet * TAK-931 80 mg Tablet + TAK-931 80 mg PIC Part 2 of the study will be initiated, once the preliminary PK data from Part 1 is available to determine the relative bioavailability of the tablet formulation in reference to PIC and to calculate the single dose of TAK-931 tablet to be used in Part 2.In Part 2, participants will be assigned to 1 of the 2 following treatment sequences: * TAK-931 TBD Fed + TAK-931 TBD Fasted * TAK-931 TBD Fasted + TAK-931 TBD Fed This multi-center trial will be conducted in the Netherlands. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic and will be contacted for approximately 30 days after receiving their last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first for a follow up assessment.
Interventions
DRUGTAK-931 PIC
TAK-931 PICs.
DRUGTAK-931 Tablet
TAK-931 Tablets.
DRUGEsomeprazole
Esomeprazole Tablets.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult participants with histologically or cytologically confirmed metastatic or locally advanced or metastatic solid tumors for whom there is no available standard treatment with proven survival benefit, this therapy is not indicated, or it is refused by the participant. Based on the nonclinical data, the following indications may have a higher probability of clinical benefit: high-grade serous ovarian cancer, uterine carcinosarcoma, squamous esophageal cancer, squamous non-small cell lung carcinoma (NSCLC), rectal adenocarcinoma, and in general tumors with known tumor protein 53 (TP53) gene mutations. For any of these preferred indications, participants should have exhausted standard therapeutic options with a proven survival benefit. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 3. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy). 4. Suitable venous access for the study-required blood sampling including PK and pharmacodynamic sampling. 5. Must have a radiographically or clinically evaluable tumor, but measurable disease as defined by RECIST v1.1 is not required for participation in this study.
Exclusion criteria
1. Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug. 2. Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, enzalutamide, mitotane, ritonavir, rifampin, or St John's wort within 14 days before the first dose of study drug. 3. With treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or CT) during the screening period. 4. Part 2 only: known hypersensitivity to PPIs (example, angioedema or anaphylaxis have occurred). 5. Part 2 only: not being able or willing to take one high fat breakfast as indicated in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length is equal to [=] 16 days) |
| Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) |
| Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931 | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | — |
| Part 1: Overall Response Rate (ORR) | Baseline up to 8 months | ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. |
| Part 1: Progression-free Survival (PFS) | From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurred first (up to 8 months) | PFS was defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occured first. Per RECIST V1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 millimeter (mm). |
| Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | — |
| Part 1: Duration of Response (DOR) | From the date of first documentation of a response to the date of first documentation of PD ( up to 8 months) | DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. |
| Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | — |
| Part 1: Percentage of Participants With Grade 3 or Higher TEAEs | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. |
| Part 1: Disease Control Rate (DCR) | Baseline up to 8 months | DCR was defined as the percentage of participants with CR, PR plus stable disease (SD) greater than or equal to (\>=) 1 post baseline computed tomography (CT) scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
| Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | — |
| Part 1, CL/F: Oral Clearance for TAK-931 | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | — |
Countries
Netherlands
Participant flow
Recruitment details
Participants took part in the study at investigative sites in the Netherlands from 28 March 2019 to 03 December 2019.
Pre-assignment details
Participants with advanced solid tumors were enrolled in 2-part cross-over design study to receive 1 of 2 treatment sequences in Part 1: TAK-931 80 mg PIC + TAK-931 80 mg tablet (Sequence A) or TAK-931 80 mg tablet + TAK-931 80 mg PIC (Sequence B). Part 2 of the study was not conducted due to the business decision, which was unrelated to safety.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Sequence A: TAK-931 80 mg PIC + TAK-931 80 mg Tablet TAK-931 80 mg, PIC, orally, once on Day 1, followed by TAK-931 80 mg tablet, orally, once on Day 3, further followed by TAK-931 50 mg PIC, orally, once daily from Days 5 to 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles, until PD, or unacceptable toxicity or any treatment discontinuation is determined. | 12 |
| Part 1, Sequence B: TAK-931 80 mg Tablet + TAK-931 80 mg PIC TAK-931 80 mg, tablet, orally, once on Day 1, followed by TAK-931 80 mg PIC, orally, once on Day 3, further followed by TAK-931 50 mg PIC, orally, once daily from Day 5 to Day 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined. | 8 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 2 | 0 |
| Overall Study | Progressive Disease | 10 | 7 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, Sequence A: TAK-931 80 mg PIC + TAK-931 80 mg Tablet | Part 1, Sequence B: TAK-931 80 mg Tablet + TAK-931 80 mg PIC | Total |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.36 | 57.6 years STANDARD_DEVIATION 12.69 | 60.6 years STANDARD_DEVIATION 10.78 |
| Body Mass Index (BMI) | 26.56 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.165 | 26.50 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.292 | 26.53 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 8 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Netherlands | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 8 |
| other Total, other adverse events | 9 / 12 | 6 / 8 |
| serious Total, serious adverse events | 2 / 12 | 2 / 8 |
Outcome results
Primary
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Population: The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC | 1901.1447 h*ng/mL | Geometric Coefficient of Variation 44.6999 |
| TAK-931 80 mg Tablet | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC | 1925.8648 h*ng/mL | Geometric Coefficient of Variation 45.2966 |
Comparison: Following log-transformation, PK parameters were analyzed by ANOVA fitting terms for treatment group, sequence and period. Participants within sequence were treated as a random effect. The obtained point estimates and adjusted 90% CIs for difference in treatment were exponentially back transformed to provide point and confidence interval estimates for the ratios of interest appropriately.90% CI: [0.9033, 1.1227]
Primary
Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Population: The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC | 1869.0329 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 44.7484 |
| TAK-931 80 mg Tablet | Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC | 1898.9016 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 45.298 |
Comparison: Following log-transformation, PK parameters were analyzed by ANOVA fitting terms for treatment group, sequence and period. Participants within sequence were treated as a random effect. The obtained point estimates and adjusted 90% CIs for difference in treatment were exponentially back transformed to provide point and confidence interval estimates for the ratios of interest appropriately.90% CI: [0.8992, 1.1201]
Primary
Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length is equal to [=] 16 days)
Population: The pharmacokinetic (PK) set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC | 251.45 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41.91 |
| TAK-931 80 mg Tablet | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC | 270.09 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.44 |
Comparison: Following log-transformation, PK parameters were analyzed by analysis of variance (ANOVA) fitting terms for treatment group, sequence and period. Participants within sequence were treated as a random effect. The obtained point estimates and adjusted 90 percent (%) confidence intervals (CIs) for difference in treatment were exponentially back transformed to provide point and confidence interval estimates for the ratios of interest appropriately.90% CI: [0.8084, 1.0835]
Secondary
Part 1, CL/F: Oral Clearance for TAK-931
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Population: The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1, CL/F: Oral Clearance for TAK-931 | 42.0799 liter per hour (L/h) | Geometric Coefficient of Variation 44.6999 |
| TAK-931 80 mg Tablet | Part 1, CL/F: Oral Clearance for TAK-931 | 41.5397 liter per hour (L/h) | Geometric Coefficient of Variation 45.2966 |
Secondary
Part 1: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with CR, PR plus stable disease (SD) greater than or equal to (\>=) 1 post baseline computed tomography (CT) scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: Baseline up to 8 months
Population: The response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 postbaseline response. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-931 80 mg PIC | Part 1: Disease Control Rate (DCR) | 18.2 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Disease Control Rate (DCR) | 25.0 percentage of participants |
Secondary
Part 1: Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm.
Time frame: From the date of first documentation of a response to the date of first documentation of PD ( up to 8 months)
Population: The response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 postbaseline response. Here overall number of participants N are those who had CR or PR. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.
Secondary
Part 1: Overall Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD.
Time frame: Baseline up to 8 months
Population: The response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 postbaseline response. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-931 80 mg PIC | Part 1: Overall Response Rate (ORR) | 0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Overall Response Rate (ORR) | 0 percentage of participants |
Secondary
Part 1: Percentage of Participants With Grade 3 or Higher TEAEs
An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.
Time frame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
Population: The safety set included all participants who received any amount of study drug. As planned, safety data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Grade 3 or Higher TEAEs | 41.7 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Grade 3 or Higher TEAEs | 37.5 percentage of participants |
Secondary
Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification
Time frame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
Population: The safety set included all participants who received any amount of study drug. As planned, safety data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | SAEs | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | TEAEs | 91.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | TEAEs Leading to Discontinuation or Dose Modification | 8.3 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | SAEs | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | TEAEs | 100 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | TEAEs Leading to Discontinuation or Dose Modification | 0 percentage of participants |
Secondary
Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters
Time frame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
Population: The safety set included all participants who received any amount of study drug. As planned, safety data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 2 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 0 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 1 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 1 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 0 to Grade 0 | 83.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 1 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 2 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 0 to Grade 0 | 33.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 3 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 0 to Grade 1 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 3 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 1 to Grade 0 | 33.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 0 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 2 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 1 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 3 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 2 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 0 to Grade 0 | 58.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 1 to Grade 2 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 0 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 1 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 1 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 2 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 1 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 0 | 41.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 2 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 3 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Bilirubin: Grade 0 to Grade 0 | 83.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Bilirubin: Grade 0 to Grade 1 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 0 | 83.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 0 | 66.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 1 | 41.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 1 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 2 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 2 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 0 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 1 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 3 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Glucose: Grade 0 to Grade 0 | 100.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 2 | 16.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 0 to Grade 0 | 50.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 4 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 0 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 1 | 41.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 1 to Grade 1 | 41.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 0 to Grade 0 | 100.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 0 | 83.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 3 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 3 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 0 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 1 to Grade 1 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 0 to Grade 0 | 33.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 0 to Grade 0 | 50.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 1 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 0 to Grade 1 | 41.7 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 0 | 33.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 1 to Grade 0 | 8.3 percentage of participants |
| TAK-931 80 mg PIC | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 0 to Grade 0 | 91.7 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 1 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 0 to Grade 0 | 87.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 0 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Eosinophils: Grade 1 to Grade 0 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 0 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 0 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 1 | 50.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 1 to Grade 3 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Hemoglobin: Grade 2 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 0 | 75.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Leukocytes: Grade 0 to Grade 3 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 0 | 50.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 0 to Grade 3 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 1 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 1 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 2 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Lymphocytes: Grade 3 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 0 | 75.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 2 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 3 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Neutrophils: Grade 0 to Grade 4 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 0 to Grade 0 | 62.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 0 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Platelets: Grade 1 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 0 to Grade 0 | 62.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 0 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 1 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alanine Aminotransferase: Grade 1 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 0 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 0 to Grade 1 | 37.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 1 to Grade 0 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 2 to Grade 0 | 37.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Alkaline Phosphatase: Grade 3 to Grade 0 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 0 to Grade 0 | 50.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 0 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 1 to Grade 0 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 1 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Aspartate Aminotransferase: Grade 2 to Grade 0 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Bilirubin: Grade 0 to Grade 0 | 87.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Bilirubin: Grade 0 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 0 | 75.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 1 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 0 to Grade 2 | 0.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Creatinine: Grade 1 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Glucose: Grade 0 to Grade 0 | 100.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 0 to Grade 0 | 50.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 0 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Magnesium: Grade 1 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 3 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 1 to Grade 1 | 12.5 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 0 to Grade 0 | 75.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Sodium: Grade 0 to Grade 1 | 25.0 percentage of participants |
| TAK-931 80 mg Tablet | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | Potassium: Grade 0 to Grade 0 | 62.5 percentage of participants |
Secondary
Part 1: Progression-free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occured first. Per RECIST V1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 millimeter (mm).
Time frame: From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurred first (up to 8 months)
Population: The safety set included all participants who received any amount of study drug. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-931 80 mg PIC | Part 1: Progression-free Survival (PFS) | 1.9 months |
| TAK-931 80 mg Tablet | Part 1: Progression-free Survival (PFS) | 2.0 months |
Secondary
Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Population: The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-931 80 mg PIC | Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931 | 7.3250 hour | Geometric Coefficient of Variation 25.4121 |
| TAK-931 80 mg Tablet | Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931 | 7.3683 hour | Geometric Coefficient of Variation 18.6369 |
Secondary
Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets
Time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Population: The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-931 80 mg PIC | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets | 1.6830 hour |
| TAK-931 80 mg Tablet | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets | 1.9830 hour |