Clinical trial NCT03482453: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 31)
measure: Part 1: Number of Participants With One or More Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 31)
measure: Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 31)
measure: Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 31)
measure: Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary outcomes:
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Parts 2 and 3: Number of Participants Reporting One or More TEAEs
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
measure: Parts 2 and 3: Number of Participants With One or More SAEs
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
measure: Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
measure: Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs
timeFrame: Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: