| Primary | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | | 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) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG000251.45± 41.91
- OG001270.09± 36.44
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| 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. | | | | | Ratio of geometric mean | 0.9359 | | | 2-Sided | 90 | 0.8084 | 1.0835 | | | | | Other | | |
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| 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 | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
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| Primary | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
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| Secondary | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets | | 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. | Posted | | Median | Full Range | hour | | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
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| Secondary | Part 1, CL/F: Oral Clearance for TAK-931 | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
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| Secondary | Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931 | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour | | Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days) | | | | ID | Title | Description |
|---|
| OG000 | TAK-931 80 mg PIC | TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, 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. | | OG001 | TAK-931 80 mg Tablet | TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, 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. |
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| 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. | 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. | Posted | | Number | | percentage of participants | | Baseline up to 8 months | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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). | 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. | Posted | | Median | 95% Confidence Interval | months | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | Part 1, Sequence B: TAK-931 80 mg Tablet + TAK-931 80 mg PIC |
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| 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. | 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. | Posted | | Number | | percentage of participants | | Baseline up to 8 months | | | | ID | Title | Description |
|---|
| OG000 | 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. |
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| 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. | 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. | Posted | | | | | | From the date of first documentation of a response to the date of first documentation of PD ( up to 8 months) | | | | ID | Title | Description |
|---|
| OG000 | 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. | |
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| Secondary | Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification | | 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. | Posted | | Number | | percentage of participants | | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | 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. | Posted | | Number | | percentage of participants | | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | | | | ID | Title | Description |
|---|
| OG000 | 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. | |
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| Secondary | Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters | | 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. | Posted | | Number | | percentage of participants | | From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months) | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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