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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-788; Drug: Placebo; Drug: TAK-788

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1 Cohort 1: TAK-788; TAK-788, capsule, orally or TAK-788 matching placebo capsule, orally, once under fasted conditions on Day 1.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788; Drug: Placebo; TAK-788 placebo-matching capsules.; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 1 Cohort 2: 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.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788; Drug: Placebo; TAK-788 placebo-matching capsules.; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 1 Cohort 3: 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.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788; Drug: Placebo; TAK-788 placebo-matching capsules.; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 1 Cohort 4: 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.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788; Drug: Placebo; TAK-788 placebo-matching capsules.; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 1 Cohort 5: 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.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788; Drug: Placebo; TAK-788 placebo-matching capsules.; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 2: TAK-788 Fed + TAK-788 Fasted; 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; TAK-788 capsules.; Other Names: AP32788; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 2: TAK-788 Fasted + TAK-788 Fed; 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; TAK-788 capsules.; Other Names: AP32788; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 3: TAK-788 DiC (reference) + TAK-788 DiC (test); 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; TAK-788 capsules.; Other Names: AP32788; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788
EXPERIMENTAL: Part 3: TAK-788 DiC (test) + TAK-788 DiC (reference); 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; TAK-788 capsules.; Other Names: AP32788; Drug: TAK-788; TAK-788 DiC.; Other Names: AP32788

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 28, 2018
• Primary Completion (ACTUAL): December 22, 2018
• Study Completion (ACTUAL): January 18, 2019

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (ACTUAL): March 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-788-1001; U1111-1208-9582 (OTHER: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No