Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to assess the safety, tolerability of TAK-788 and to identify a tolerable single oral dose of TAK-788 administered as a drug-in-capsule (DiC) formulation, to characterize the effects of a low-fat meal on the PK of the TAK-788 administered as DiC formulation and to evaluate the bioavailability of a test (Process B) DiC of TAK-788 relative to a reference (Process A) DiC of TAK-788 in healthy participants.
Detailed description
The drug being tested in this study is called TAK-788. The study will assess the safety and tolerability of single oral dose of TAK-788, evaluate the effect of a low-fat meal on PK of TAK-788 and will assess the relative bioavailability of two DiCs of TAK-788. The study will enroll approximately 69 participants. The study is designed to consist of 3 parts: Part 1- dose escalation phase, Part 2- low fat meal effect and Part 3 - relative bioavailability. The study population of Part 1 will consist of 40 participants enrolled into 5 cohorts. Each cohort will have 8 randomized participants with 6 receiving a single dose of TAK-788, and 2 receiving matching placebo under fasted conditions. In Cohorts 1 to 5, safety of single-dose TAK-788 will be evaluated. For Part 2, the effect of a low-fat meal on a single tolerable dose of TAK-788 will be determined following review of safety and tolerability data from the previous cohorts in Part 1. The study population of Part 2 will consist of 16 participants enrolled into 2 cohorts of different doses, where participants will be randomized to a cross-over sequence of: * TAK-788 Fed + TAK-788 Fasted * TAK-788 Fasted + TAK-788 Fed The study population of Part 3 will consist of 13 participants enrolled into 1 cohort, where participants will be randomized to a cross-over sequence of: * TAK-788 DiC (reference) + TAK-788 DiC (test) * TAK-788 DiC (test) + TAK-788 DiC (reference) This single-center trial will be conducted in the United States. The overall time to participate in this study is approximately 7 months. Participants will be contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-788
TAK-788 capsules.
DRUGPlacebo
TAK-788 placebo-matching capsules.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Body weight of greater than or equal to (\>=) 45 kilogram (kg) (women) or \>=55 kg (men) and a body mass index of 18.0 to 30.0 kilogram per square meter (kg/m\^2) at screening. 2. Nonsmoker (never smoked or greater than \[\>\] 20 years from last occurrence of smoking). 3. Normal organ function including hepatic, renal, and bone marrow function.
Exclusion criteria
1. Manifestations of malabsorption due to prior gastro-intestinal (GI) surgery, GI disease, or for an unknown other reason that may alter the PK of TAK-788. 2. Pulmonary infection ongoing or within 30 days of informed consent. 3. Inability to undergo venipuncture and/or tolerate venous access. 4. Inability to tolerate multiple blood sampling. 5. Ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to 30 days after the last dose of study drug (Day 31) |
| Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | Baseline up to 30 days after the last dose of study drug (Day 31) |
| Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | Baseline up to 30 days after the last dose of study drug (Day 31) |
| Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | Baseline up to 30 days after the last dose of study drug (Day 31) |
Secondary
| Measure | Time frame |
|---|---|
| Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
| Parts 2 and 3: Number of Participants Reporting One or More TEAEs | Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2) |
| Parts 2 and 3: Number of Participants With One or More SAEs | Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2) |
| Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2) |
| Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2) |
| Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 28 March 2018 to 18 January 2019.
Pre-assignment details
Healthy participants were enrolled in this 3 parts study to receive: TAK-788 as a single rising dose of 20 milligram (mg), 40 mg, 80 mg, 120 mg, 160 mg in Part 1; TAK-788 in a 2-way cross-over design with or without a low-fat meal in Part B; or in a 2-way cross-over sequence to receive TAK-788 drug in capsule (DiC) A or B in Part 3.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Pooled Placebo TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1. | 10 |
| Part 1 Cohort 1: TAK-788 20 mg TAK-788 20 mg, capsule, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 2: TAK-788 40 mg TAK-788 40 mg, capsule, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 3: TAK-788 80 mg TAK-788 80 mg, capsule, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 4: TAK-788 120 mg TAK-788 120 mg, capsule, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 5: TAK-788 160 mg TAK-788 160 mg, capsule, orally, once under fasted conditions on Day 1. | 6 |
| Part 2: TAK-788 120 mg Fed + TAK-788 120 mg Fasted TAK-788 120 mg, capsule, orally, once on Day 1 of Intervention Period 1 under fed conditions with low-fat meal (Treatment A), followed by at least 7 days washout period, further followed by TAK-788, 120 mg, capsule, orally, once on Day 1 of Intervention Period 2 under fasted conditions (Treatment B). | 3 |
| Part 2: TAK-788 120 mg Fasted + TAK-788 120 mg Fed TAK-788, 120 mg, capsule, orally, once on Day 1 of Intervention Period 1 under fasted conditions (Treatment B), followed by at least 7 days washout period, further followed by TAK-788, 120 mg, capsule, orally, once on Day 1 of Intervention Period 2 under fed conditions with low-fat meal (Treatment A). | 3 |
| Part 2: TAK-788 160 mg Fed + TAK-788 160 mg Fasted TAK-788 160 mg, capsule, orally, once on Day 1 of Intervention Period 1 under fed conditions with low-fat meal (Treatment A), followed by at least 7 days washout period, further followed by TAK-788 160 mg, capsule, orally, once on Day 1 of Intervention Period 2 under fasted conditions (Treatment B). | 5 |
| Part 2: TAK-788 160 mg Fasted + TAK-788 160 mg Fed TAK-788, 160 mg, capsule, orally, once on Day 1 of Intervention Period 1 under fasted conditions (Treatment B), followed by at least 7 days washout period, further followed by TAK-788, 160 mg, capsule, orally, once on Day 1 of Intervention Period 2 under fed conditions with low-fat meal (Treatment A). | 5 |
| Part 3: TAK-788 DiC A + TAK-788 DiC B TAK-7 160 mg, DiC A (reference), orally, under fasted condition, once on Day 1 of Intervention Period 1, followed by at least 7 days washout period, further followed by TAK-788 160 mg, DiC B (test), orally, under fasted condition, once on Day 1 of Intervention Period 2. | 7 |
| Part 3: TAK-788 DiC B + TAK-788 DiC A TAK-788 160 mg, DiC B (test), orally, under fasted condition, once on Day 1 of Intervention Period 1, followed by at least 7 days washout period, further followed by TAK-788 160 mg, DiC A (reference), orally, under fasted condition, once on Day 1 of Intervention Period 2. | 6 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts 2, 3 Intervention Period 1 (1 Day) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part 1 Cohort 1: TAK-788 20 mg | Part 1 Cohort 2: TAK-788 40 mg | Part 1 Cohort 3: TAK-788 80 mg | Part 1: Pooled Placebo | Part 1 Cohort 4: TAK-788 120 mg | Part 1 Cohort 5: TAK-788 160 mg | Part 2: TAK-788 120 mg Fed + TAK-788 120 mg Fasted | Part 2: TAK-788 120 mg Fasted + TAK-788 120 mg Fed | Part 2: TAK-788 160 mg Fed + TAK-788 160 mg Fasted | Part 2: TAK-788 160 mg Fasted + TAK-788 160 mg Fed | Part 3: TAK-788 DiC A + TAK-788 DiC B | Part 3: TAK-788 DiC B + TAK-788 DiC A |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 69 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 5 Participants | 5 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 5 Participants | 5 Participants | 5 Participants | 9 Participants | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 4 Participants | 5 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 66 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 7 Participants | 5 Participants |
| Region of Enrollment United States | 69 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 5 Participants | 5 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Female | 17 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 52 Participants | 6 Participants | 5 Participants | 4 Participants | 7 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 2 / 10 | 2 / 6 | 3 / 6 | 4 / 6 | 3 / 6 | 5 / 6 | 3 / 6 | 3 / 6 | 7 / 10 | 5 / 10 | 4 / 13 | 4 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 13 | 0 / 12 |
Outcome results
Primary
Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to 30 days after the last dose of study drug (Day 31)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
Primary
Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values
Time frame: Baseline up to 30 days after the last dose of study drug (Day 31)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
Primary
Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs
Time frame: Baseline up to 30 days after the last dose of study drug (Day 31)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
Primary
Part 1: Number of Participants With One or More Serious Adverse Events (SAEs)
Time frame: Baseline up to 30 days after the last dose of study drug (Day 31)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Part 1: Number of Participants With One or More Serious Adverse Events (SAEs) | 0 Participants |
Primary
Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 533.8 h*ng/mL | Standard Deviation 272.07 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 525.8 h*ng/mL | Standard Deviation 301.84 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 706.3 h*ng/mL | Standard Deviation 294.61 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 743.0 h*ng/mL | Standard Deviation 462.07 |
90% CI: [0.8977, 1.1483]
90% CI: [0.874, 1.0339]
Primary
Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 526.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 272.72 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 518.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 300.84 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 700.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 295.1 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 733.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 461.41 |
Primary
Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The pharmacokinetic (PK) set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 27.52 nanogram per milliliter (ng/mL) | Standard Deviation 11.423 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 31.24 nanogram per milliliter (ng/mL) | Standard Deviation 16.682 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 39.51 nanogram per milliliter (ng/mL) | Standard Deviation 17.179 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 41.00 nanogram per milliliter (ng/mL) | Standard Deviation 21.917 |
90% CI: [0.7108, 1.0921]
90% CI: [0.8361, 1.1107]
Primary
Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 17.17 hour | Standard Deviation 2.629 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 17.60 hour | Standard Deviation 4.067 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 20.72 hour | Standard Deviation 4.827 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 20.62 hour | Standard Deviation 6.854 |
Primary
Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pooled Placebo | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 6.0 hour |
| Part 1 Cohort 1: TAK-788 20 mg | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 4.0 hour |
| Part 1 Cohort 2: TAK-788 40 mg | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 6.0 hour |
| Part 1 Cohort 3: TAK-788 80 mg | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 6.0 hour |
Primary
Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 738.8 h*ng/mL | Standard Deviation 193.06 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 | 709.5 h*ng/mL | Standard Deviation 262.84 |
90% CI: [0.8861, 1.0408]
Primary
Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 706.1 h*ng/mL | Standard Deviation 173.63 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 | 677.9 h*ng/mL | Standard Deviation 239.28 |
Primary
Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 44.77 ng/mL | Standard Deviation 14.738 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788 | 41.71 ng/mL | Standard Deviation 11.931 |
90% CI: [0.8458, 1.0263]
Primary
Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 16.38 hour | Standard Deviation 2.007 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 | 16.38 hour | Standard Deviation 2.858 |
Primary
Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pooled Placebo | Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 6.0 hour |
| Part 1 Cohort 1: TAK-788 20 mg | Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 | 5.0 hour |
Secondary
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 63.6 h*ng/mL | Standard Deviation 7.11 |
| Part 1: Pooled Placebo | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | NA h*ng/mL | — |
| Part 1: Pooled Placebo | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 37.4 h*ng/mL | Standard Deviation 6.23 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 79.8 h*ng/mL | Standard Deviation 22.41 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 160.4 h*ng/mL | Standard Deviation 115.57 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 19.27 h*ng/mL | Standard Deviation 3.111 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 165.9 h*ng/mL | Standard Deviation 81.28 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 256.9 h*ng/mL | Standard Deviation 203.43 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 20.34 h*ng/mL | Standard Deviation 12.714 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 456.1 h*ng/mL | Standard Deviation 187.2 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 34.58 h*ng/mL | Standard Deviation 11.482 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 293.4 h*ng/mL | Standard Deviation 124.35 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 548.0 h*ng/mL | Standard Deviation 198.24 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 1017.3 h*ng/mL | Standard Deviation 599.11 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 85.16 h*ng/mL | Standard Deviation 48.623 |
Secondary
Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | TAK-788 | 59.4 h*ng/mL | Standard Deviation 7.07 |
| Part 1: Pooled Placebo | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32914 | NA h*ng/mL | — |
| Part 1: Pooled Placebo | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32960 | 32.7 h*ng/mL | Standard Deviation 6.41 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32960 | 74.9 h*ng/mL | Standard Deviation 21.89 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | TAK-788 | 155.2 h*ng/mL | Standard Deviation 112.06 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32914 | 11.53 h*ng/mL | Standard Deviation 6.092 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32960 | 159.3 h*ng/mL | Standard Deviation 77.04 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | TAK-788 | 250.4 h*ng/mL | Standard Deviation 197.25 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32914 | 14.59 h*ng/mL | Standard Deviation 11.845 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | TAK-788 | 448.3 h*ng/mL | Standard Deviation 184.43 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32914 | 31.74 h*ng/mL | Standard Deviation 11.37 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32960 | 284.0 h*ng/mL | Standard Deviation 125.52 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32960 | 538.5 h*ng/mL | Standard Deviation 196.1 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | TAK-788 | 1007.8 h*ng/mL | Standard Deviation 596.14 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914 | Metabolite AP32914 | 80.40 h*ng/mL | Standard Deviation 47.696 |
Secondary
Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 3.22 ng/mL | Standard Deviation 0.938 |
| Part 1: Pooled Placebo | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | NA ng/mL | — |
| Part 1: Pooled Placebo | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 1.546 ng/mL | Standard Deviation 0.4914 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 3.483 ng/mL | Standard Deviation 0.8827 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 7.85 ng/mL | Standard Deviation 4.206 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 0.735 ng/mL | Standard Deviation 0.2221 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 8.298 ng/mL | Standard Deviation 5.5055 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 14.66 ng/mL | Standard Deviation 11.649 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 1.315 ng/mL | Standard Deviation 1.0492 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 25.81 ng/mL | Standard Deviation 9.682 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 2.036 ng/mL | Standard Deviation 0.6433 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 13.417 ng/mL | Standard Deviation 5.5667 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 25.411 ng/mL | Standard Deviation 10.7473 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 52.21 ng/mL | Standard Deviation 27.681 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 4.051 ng/mL | Standard Deviation 1.8778 |
Secondary
Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 18.07 hour | Standard Deviation 1.477 |
| Part 1: Pooled Placebo | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | NA hour | — |
| Part 1: Pooled Placebo | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 23.96 hour | Standard Deviation 3.461 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 21.43 hour | Standard Deviation 2.979 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 15.95 hour | Standard Deviation 4.593 |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 13.75 hour | Standard Deviation 3.323 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 22.19 hour | Standard Deviation 1.137 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 14.25 hour | Standard Deviation 4.31 |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 12.22 hour | Standard Deviation 2.084 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 18.30 hour | Standard Deviation 1.286 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 12.02 hour | Standard Deviation 1.162 |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 28.93 hour | Standard Deviation 5.903 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 29.18 hour | Standard Deviation 6.368 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 19.85 hour | Standard Deviation 5.464 |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 16.09 hour | Standard Deviation 4.548 |
Secondary
Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK set included all participants in the safety set who had no major protocol deviations that would have affected the PK analysis and who had sufficient data to calculate PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Pooled Placebo | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 6.0 hour |
| Part 1: Pooled Placebo | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | NA hour |
| Part 1: Pooled Placebo | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 6.0 hour |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 4.0 hour |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 5.0 hour |
| Part 1 Cohort 1: TAK-788 20 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 6.0 hour |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 4.0 hour |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 4.0 hour |
| Part 1 Cohort 2: TAK-788 40 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 4.0 hour |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 6.0 hour |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 6.0 hour |
| Part 1 Cohort 3: TAK-788 80 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 6.0 hour |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32960 | 5.0 hour |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | TAK-788 | 6.0 hour |
| Part 1 Cohort 4: TAK-788 120 mg | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914 | Metabolite AP32914 | 6.0 hour |
Secondary
Parts 2 and 3: Number of Participants Reporting One or More TEAEs
Time frame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 3 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 3 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 7 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 5 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 4 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Parts 2 and 3: Number of Participants Reporting One or More TEAEs | 4 Participants |
Secondary
Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values
Time frame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values | 0 Participants |
Secondary
Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs
Time frame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs | 0 Participants |
Secondary
Parts 2 and 3: Number of Participants With One or More SAEs
Time frame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Population: The safety set included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pooled Placebo | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |
| Part 1 Cohort 1: TAK-788 20 mg | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |
| Part 1 Cohort 2: TAK-788 40 mg | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |
| Part 1 Cohort 3: TAK-788 80 mg | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |
| Part 1 Cohort 4: TAK-788 120 mg | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |
| Part 1 Cohort 5: TAK-788 160 mg | Parts 2 and 3: Number of Participants With One or More SAEs | 0 Participants |