TAK-114 Single- and Multiple-Dose Phase 1 Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of TAK-114 following single and multiple ascending oral doses in healthy Japanese male participants.

Detailed Description
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This is a phase 1, randomized, double-blind, placebo-controlled, single and multiple oral dose study in healthy Caucasian and Japanese male participants. The study is composed of three parts, Single-dose Ascending Part, Food Effect Part and Multiple-dose Ascending Part. Single-dose Ascending Part and Multiple-dose Ascending Part are designed as a randomized, double-blind or open-label, placebo-controlled, sequential-cohort, ascending single or multiple oral dose study of TAK-114 or matched placebo. The Food Effect Part is designed as a randomized, open-label, 2-period crossover study of a single dose of TAK-114.

Official Title
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A Single-center, Single- and Multiple-Dose Phase 1 Study to Evaluate the Safety and Pharmacokinetics of TAK-114 in Healthy Adult Japanese and Caucasian Male Subjects

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: TAK-114 10 mg capsule
* Drug: TAK-114 matched placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese participants: Must be willing to provide written informed consent and in the investigator's opinion able to comply with the study protocol. Is aged 20 to 45 years, inclusive. Weighs at least 50 kilogram (kg) and have a body mass index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m^2). Healthy Caucasian participants: Must be willing to provide written informed consent and in the investigator's opinion able to comply with the study protocol. Is aged 20 to 45 years, inclusive; are of Caucasian descent (born to Caucasian parents and grandparents and has lived outside original country for less than 5 years) and maintains their original diet and lifestyle. Weighs at least 50 kg and have a body mass index between 18.5 and 30.0 kg/m2. Exclusion Criteria: • Participants have a known hypersensitivity to any component of the formulation of TAK-114 or any herb medicine or supplement related to Indigo naturalis.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1A: TAK-114 10 mg<br>Orally, once only. | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 1B: TAK-114 10 mg<br>Orally, once | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 2A: TAK-114 20 mg<br>Orally, once | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 2B: TAK-114 20 mg<br>Orally, once | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 3A: TAK-114 50 mg<br>Orally, once | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 3B: TAK-114 50 mg<br>Orally, once | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 4a: TAK-114 20 mg<br>Period 1: Single-dose administration in a fasting state Period 2: Single-dose administration 30 minutes after breakfast | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 4b: TAK-114 20 mg<br>Period 1: Single-dose administration 30 minutes after breakfast Period 2: Single-dose administration in a fasting state | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 5A: TAK-114 20 mg<br>Orally, Twice daily, 10 days | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 5B: TAK-114 20 mg<br>Orally, Twice daily, 10 days | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 6A: TAK-114 50 mg<br>Orally, Twice daily, 10 days | Drug: TAK-114 10 mg capsule<br> <br> |
| Experimental: Cohort 6B: TAK-114 50 mg<br>Orally, Twice daily, 10 days | Drug: TAK-114 10 mg capsule<br> <br> |
| Placebo Comparator: Cohort 1A, 2A, 3A: TAK-114 placebo<br>Cohort 1A, 2A, 3A: Orally, once | Drug: TAK-114 matched placebo<br> <br> |
| Placebo Comparator: Cohort 5A: TAK-114 placebo<br>Cohort 5A: Orally, Twice daily, 10 days | Drug: TAK-114 matched placebo<br> <br> |
| Placebo Comparator: Cohort 6A: TAK-114 placebo<br>Cohort 6A: Orally, Twice daily, 10 days | Drug: TAK-114 matched placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) |  | Baseline up to 3 days after the last dose of study drug (Day 3 in Part 1), (Day 20 in Part 2) and 7 days after the last dose of study drug (Day 17 in Part 3) | 
| Number of Participants With TEAEs Related to Vital Signs |  | Baseline up to Day 3 in Part 1, Day 20 in Part 2 and Day 17 in Part 3 | 
| Number of Participants With TEAEs Related to Body Weight |  | Baseline up to Day 3 in Part 1, Day 20 in Part 2 and Day 17 in Part 3 | 
| Number of Participants With Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | Number of participants who had ECG shifts from within normal limit at baseline to abnormal, clinically significant after study drug administration were reported. | Baseline up to Day 3 in Part 1, Day 20 in Part 2 and Day 17 in Part 3 | 
| Number of Participants With Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) |  | Baseline up to Day 2 (only for Cohorts 1A, 2A, and 3A) in Part 1 | 
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis |  | Baseline up to Day 3 in Part 1, Day 20 in Part 2 and Day 17 in Part 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Plasma Concentration for TAK-114 |  | Day1: predose and at multiple time-points (up to 48 hours) postdose for Part 1; Day 1:predose and at multiple time-points (up to 48 hours) postdose in each period for Part 2; Day 10:predose and at multiple time points (up to 12 hours) postdose for Part 3 | 
| AUC (0-Infinity) - Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Unchanged TAK-114: Part 1 and Part 2 |  | Day 1: predose and at multiple time-points (up to 48 hours) postdose for Part 1; Day 1: predose and at multiple time-points (up to 48 hours) postdose in each period for Part 2 | 
| AUC (0-tau) - Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau for TAK-114: Part 3 |  | Day10: predose and at multiple time points (up to 12 hours) postdose for Part 3 | 
| Mean Terminal Phase Elimination Half-life (T1/2) for TAK-114 |  | Day1:predose and at multiple time-points (up to 48 hours) postdose for Part 1; Day1:predose and at multiple time-points (up to 48 hours) postdose in each period for Part 2; Day 10: predose and at multiple time points (up to 12 hours) postdose for Part 3 | 
| Mean R(Cmax): Mean Accumulation Coefficient of Observed Maximum Plasma Concentration for TAK-114: Part 3 | Mean R(Cmax) was estimated as the ratio of Cmax on Day 10 and Cmax on Day 1. Cmax is the peak plasma drug concentration of TAK-114. | Days 1 and 10: predose and at multiple time points (up to 12 hours) postdose for Part 3 | 
| Mean R(AUC): Mean of Accumulation Coefficient of Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-114: Part 3 | Mean R(AUC) was estimated as the ratio of AUC(0-tau) on Day 10 and AUC(0-tau) on Day 1. AUC (0-tau) is the area under the plasma concentration-time curve from time 0 to time tau. | Days 1 and 10: predose and at multiple time points (up to 12 hours) postdose for Part 3 | 
| Urinary Excretion Ratio of TAK-114 From 0 to 48 Hours Postdose: Part 1 | Urinary excretion ratio (% of dose) of TAK-114 in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected. | Day 1: 0 to 48 hours postdose |