A Pharmacokinetic Study of TAK-438 in Healthy Adult Chinese Participants

An Open-Label, Single-center, Parallel, Phase 1 Study to Determine the Pharmacokinetics of Single- and Multiple- Oral Doses of TAK-438 10 mg and 20 mg in Healthy Adult Chinese Subjects

The purpose of this study is to determine the pharmacokinetics (PK) of TAK-438 in healthy adult Chinese participants after both single and multiple dose administration.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: TAK-438

Detailed Description

The drug being tested in this study is called TAK-438. TAK-438 is being tested in healthy participants in order to evaluate the PK of single and multiple oral dose.

The study will enroll approximately 36 healthy participants. Participants will be assigned to one of the three treatment groups:

• TAK-438 10 mg tablet once daily
• TAK-438 20 mg tablet once daily
• TAK-438 20 mg tablet twice daily All participants will be asked to take TAK-438 tablet at the same time on Day 1 and Days 3-9.

This single-centre trial will be conducted in China. The overall time to participate in this study is 18 days. Participants will remain confined to the clinic from Day 1 up to Day 11 and will be followed-up by telephone or visit on Day 18.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is a healthy adult male or female Chinese participant.
2. Is aged 18 to 45 years, inclusive, at the time of signing the informed consent form.
3. Weighs at least 50 kilogram (kg) and has a body mass index (BMI) between 19 and 26 kilogram per square meter (kg/m^2), inclusive at Screening (Check-In Day -1).
4. Is willing to abstain from caffeine and alcohol from 72 hours before first dose (Day 1) until the Follow-up Visit on Day 18.
5. Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1) until the Follow-up Visit on Day 18.
6. Is willing to provide a sample for pharmacogenetic analysis (for cytochrome [CYP2C19] genotyping).

Exclusion Criteria:

1. Has uncontrolled, clinically significant cardiovascular disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
2. Is lactose intolerant or has a known hypersensitivity to any component of the formulation of TAK-438.
3. Has poor peripheral venous access.
4. Has donated or lost 400 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Day 1; or participant has donated or lost more than 200 mL or more of his or her blood in the last 28 days.
5. Has a history of symptomatic gastroesophageal reflux disease (GERD), Erosive Esophagitis, duodenal ulcer (DU), gastric ulcer (GU), dyspepsia, Barrett's Esophagus, or Zollinger-Ellison (ZE) syndrome or has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-438 10 milligram (mg) Once Daily; TAK-438 10 mg, tablets, orally, once daily on Days 1, 3-9. Participants were required to fast for a minimum of 10 hours prior administration of assigned treatment.	Drug: TAK-438; TAK-438 tablets.
Experimental: TAK-438 20 mg Once Daily; TAK-438 20 mg, tablets, orally, once daily on Days 1, 3-9. Participants were asked to fast for a minimum of 10 hours prior administration of assigned treatment.	Drug: TAK-438; TAK-438 tablets.
Experimental: TAK-438 20 mg Twice Daily; TAK-438 20 mg, tablets, orally, once on Day 1 and twice daily on Days 3-9. Participants were asked to fast for a minimum of 10 hours prior to breakfast, followed by administration of assigned treatment 0.5 hours after breakfast and dinner.	Drug: TAK-438; TAK-438 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-438 (TAK-438F) and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over the Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
T1/2z: Terminal Disposition Half-life for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
Cmax,ss: Maximum Observed Plasma Concentration, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose
Tmax, ss: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose
AUCτ,ss: Area Under the Plasma Concentration-time Curve During a Dosing Interval, at Steady State for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose
Aet: Total Amount of Drug Excreted in Urine From Time 0 to Time T for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
Fe,t: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
CLr: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 1	Day 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose
Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose
Fe,τ: Fraction of Administered Dose of Drug Excreted in Urine During a Dosing Interval for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose
CLR: Renal Clearance for TAK-438F and Its Metabolites M-I, M-II, M-III and M-IV-Sul on Day 9	Day 9 pre-dose and at multiple timepoints (up to 24 hours for TAK-483 10 mg once daily and 20 mg once daily; up to 12 hours for TAK-438 20 mg twice daily) post-dose

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2017
• Primary Completion (Actual): August 17, 2017
• Study Completion (Actual): August 17, 2017

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-438_114; U1111-1191-6949 (Registry Identifier: WHO); CTR20170137 (Registry Identifier: CFDA)

Drug and device information, study documents

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