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

Phase 1

Completed

• Conditions: Clinical Pharmacology
• Interventions: Drug: TAK-114 10 mg capsule; Drug: TAK-114 matched placebo

• Registration Number: NCT02286518
• Lead Sponsor: Takeda

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-11
• Study First Submitted: 2014-11-05
• Study First Submitted QC: 2014-11-05
• Study First Posted: 2014-11-07
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Results First Submitted: 2016-04-27
• Status Verified: 2016-06
• Results First Submitted QC: 2016-06-13
• Last Update Submitted: 2016-06-13
• Results First Posted: 2016-07-25
• Last Update Posted: 2016-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 82

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 5A: TAK-114 20 mg	TAK-114 10 mg capsule	Orally, Twice daily, 10 days
Cohort 1A: TAK-114 10 mg	TAK-114 10 mg capsule	Orally, once only.
Cohort 2A: TAK-114 20 mg	TAK-114 10 mg capsule	Orally, once
Cohort 4a: TAK-114 20 mg	TAK-114 10 mg capsule	Period 1: Single-dose administration in a fasting state Period 2: Single-dose administration 30 minutes after breakfast
Cohort 2B: TAK-114 20 mg	TAK-114 10 mg capsule	Orally, once
Cohort 3A: TAK-114 50 mg	TAK-114 10 mg capsule	Orally, once
Cohort 3B: TAK-114 50 mg	TAK-114 10 mg capsule	Orally, once
Cohort 4b: TAK-114 20 mg	TAK-114 10 mg capsule	Period 1: Single-dose administration 30 minutes after breakfast Period 2: Single-dose administration in a fasting state
Cohort 5B: TAK-114 20 mg	TAK-114 10 mg capsule	Orally, Twice daily, 10 days
Cohort 6B: TAK-114 50 mg	TAK-114 10 mg capsule	Orally, Twice daily, 10 days
Cohort 1A, 2A, 3A: TAK-114 placebo	TAK-114 matched placebo	Cohort 1A, 2A, 3A: Orally, once
Cohort 5A: TAK-114 placebo	TAK-114 matched placebo	Cohort 5A: Orally, Twice daily, 10 days
Cohort 6A: TAK-114 placebo	TAK-114 matched placebo	Cohort 6A: Orally, Twice daily, 10 days
Cohort 6A: TAK-114 50 mg	TAK-114 10 mg capsule	Orally, Twice daily, 10 days
Cohort 1B: TAK-114 10 mg	TAK-114 10 mg capsule	Orally, once

Primary Outcome Measures

Name	Time	Method
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)	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

Name	Time	Method
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	Days 1 and 10: predose and at multiple time points (up to 12 hours) postdose for 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.
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	Days 1 and 10: predose and at multiple time points (up to 12 hours) postdose for 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.
Urinary Excretion Ratio of TAK-114 From 0 to 48 Hours Postdose: Part 1	Day 1: 0 to 48 hours postdose	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.