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

 -  Male subjects aged 18 to 45, inclusive, who are in good health, as determined by
 medical history, physical examination, clinical laboratory evaluations and urine drug
 screen

 -  The subject has the ability to tolerate the pH probe for 24 hours prior to
 Randomization (Day 1).

 Exclusion Criteria:

 -  Clinically significant history of hypersensitivity to any drug or food or any
 excipients of TAK-438.

 -  History of gastroesophageal reflux disease (GERD), symptomatic GERD, erosive
 esophagitis, duodenal ulcer,gastric ulcer, dyspepsia, Barrett's esophagus, or
 Zollinger-Ellison syndrome

 -  The subject has a positive test result for Helicobacter pylori at the Initial
 Screening Visit.

 -  Any clinically significant results from physical examinations or clinical laboratory
 results as deemed by the investigator.