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
- Registration Number
- NCT03482453
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 1: TAK-788 Placebo TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1. Part 1 Cohort 2: TAK-788 Placebo 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. Part 1 Cohort 3: TAK-788 TAK-788 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. Part 1 Cohort 3: TAK-788 Placebo 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. Part 1 Cohort 4: TAK-788 Placebo 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. Part 1 Cohort 5: TAK-788 Placebo 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. Part 2: TAK-788 Fed + TAK-788 Fasted TAK-788 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. Part 2: TAK-788 Fasted + TAK-788 Fed TAK-788 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. Part 1 Cohort 2: TAK-788 TAK-788 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. Part 1 Cohort 5: TAK-788 TAK-788 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. Part 1 Cohort 1: TAK-788 TAK-788 TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1. Part 1 Cohort 4: TAK-788 TAK-788 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. Part 3: TAK-788 DiC (reference) + TAK-788 DiC (test) TAK-788 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. Part 3: TAK-788 DiC (test) + TAK-788 DiC (reference) TAK-788 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.
- Primary Outcome Measures
Name Time Method 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 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 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, 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, 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 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
- Secondary Outcome Measures
Name Time Method 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 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 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 Reporting One or More TEAEs Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2) 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 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)
Trial Locations
- Locations (1)
PRA Health Sciences
🇺🇸Salt Lake City, Utah, United States