NCT02141698

Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential-Panel, Ascending Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 73 (actual)
• Sponsor: Takeda · Industry
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

The primary purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of TAK-438 following single or multiple doses of TAK-438 in healthy Western men, to investigate the effect of food on the pharmacokinetics of TAK-438, and to compare the TAK-438 pharmacokinetics of Western with Japanese men.

Detailed description

The drug being tested in this study is called TAK-438. TAK-438 is being tested to find a safe and well-tolerated dose. This study looked at the pharmacodynamic and pharmacokinetic properties (how the drug moves throughout the body) of the drug and safety (lab results and side effects) in people who took TAK-438. This study was designed to consist of 4 sequential substudies: a single rising dose study (Cohorts 1 to 7), a food-effect study (Cohort 8), a multiple rising dose study (Cohorts 9 to 11), and a Japanese bridging study (Cohort 12). However, the protocol was halted during the food effect study (Cohort 8) following the discovery of previously unidentified metabolites and as a result, the multiple rising dose (Cohorts 9-11) and ethnicity (Cohort 12) studies were not carried out. The study population for each of Cohorts 1 to 7 consisted of 9 subjects; with 6 subjects randomized to receive a single dose of TAK-438, and 3 subjects to receive placebo. Subjects in Cohorts 1 to 7 received a single dose of study drug after a 10-hour fast. The starting dose was 1 mg followed by administrations of 5, 10, 20, 15, 40, and 30 mg. In Cohort 8 the plan was to assign 12 participants in a 2-sequence, 2-period crossover design. Six participants were to receive a single dose of TAK-438 on Day 1, in the fasted state, followed by a second single dose of TAK-438 on Day 15 in the alternative fed state. The other 6 participants were to receive the study drug like-wise but in the fed then fasted state. To investigate the effect of multiple dosing, a further 3 cohorts (Cohorts 9-11), each comprising 12 participants were to be introduced to the protocol following completion of the single rising dose study. A final cohort, Cohort 12, consisting of 24 Western participants and 24 Japanese participants was to be used to assess the effect of TAK-438 and esomeprazole on the safety, tolerability, pharmacokinetics and pH of the stomach between these 2 ethnic groups. This single-centre trial was conducted in the United Kingdom.

Conditions

• Dose Finding Study

Interventions

Type	Name	Description
DRUG	TAK-438	TAK-438 tablets
DRUG	TAK-438 Placebo	TAK-438 placebo-matching tablets
DRUG	Esomeprazole	Esomeprazole tablets

Timeline

• Start date: 2007-10-01
• Primary completion: 2008-02-01
• Completion: 2008-02-01
• First posted: 2014-05-19
• Last updated: 2014-05-19