A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1, Randomized, Double-blind, Placebo-Controlled, Single Rising Dose Study to Evaluate Pharmacokinetics, Safety, and Tolerability of TAK-788 Followed by Open-Label, Crossover Evaluation of the Effects of a Low-Fat Meal on TAK-788 Pharmacokinetics and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TAK-788
* Drug: Placebo
* Drug: TAK-788


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Nonsmoker (never smoked or greater than [>] 20 years from last occurrence of smoking). Normal organ function including hepatic, renal, and bone marrow function. Exclusion Criteria: 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. Pulmonary infection ongoing or within 30 days of informed consent. Inability to undergo venipuncture and/or tolerate venous access. Inability to tolerate multiple blood sampling. Ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort 1: TAK-788<br>TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;Drug: Placebo<br>* TAK-788 placebo-matching capsules.<br>|
| Experimental: Part 1 Cohort 2: TAK-788<br>TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 1. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;Drug: Placebo<br>* TAK-788 placebo-matching capsules.<br>|
| Experimental: Part 1 Cohort 3: TAK-788<br>TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 2. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;Drug: Placebo<br>* TAK-788 placebo-matching capsules.<br>|
| Experimental: Part 1 Cohort 4: TAK-788<br>TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 3. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;Drug: Placebo<br>* TAK-788 placebo-matching capsules.<br>|
| Experimental: Part 1 Cohort 5: TAK-788<br>TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1 following review of safety data from Cohort 4. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;Drug: Placebo<br>* TAK-788 placebo-matching capsules.<br>|
| Experimental: Part 2: TAK-788 Fed + TAK-788 Fasted<br>TAK-788, 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, capsule, orally, once on Day 1 of Intervention Period 2 under fasted conditions (Treatment B). TAK-788 dose will be determined based on review of safety and tolerability data from cohorts of Part 1. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;|
| Experimental: Part 2: TAK-788 Fasted + TAK-788 Fed<br>TAK-788, 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, capsule, orally, once on Day 1 of Intervention Period 2 under fed conditions with low-fat meal (Treatment A). TAK-788 dose will be determined based on review of safety and tolerability data from cohorts of Part 1. | Drug: TAK-788<br>* TAK-788 capsules.<br>* Other names: AP32788;|
| Experimental: Part 3: TAK-788 DiC (reference) + TAK-788 DiC (test)<br>TAK-788 160 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. | Drug: TAK-788<br>* TAK-788 DiC.<br>* Other names: AP32788;|
| Experimental: Part 3: TAK-788 DiC (test) + TAK-788 DiC (reference)<br>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. | Drug: TAK-788<br>* TAK-788 DiC.<br>* Other names: AP32788;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy