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

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

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.

Study Overview

• Status: Completed
• Conditions: Clinical Pharmacology
• Intervention / Treatment: Drug: TAK-114 10 mg capsule; Drug: TAK-114 matched placebo

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Sumida-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

15

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Chair: General Manager, Takeda

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: November 5, 2014
• First Posted (Estimate): November 7, 2014

Study Record Updates

• Last Update Posted (Estimate): July 25, 2016
• Last Update Submitted That Met QC Criteria: June 13, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: TAK-114/CPH-001; U1111-1162-6078 (Registry Identifier: WHO); JapicCTI-142691 (Registry Identifier: JapicCTI (Japan))