Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects
Condition: Dose Finding Study
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): TAK-438; TAK-438 Placebo; Esomeprazole
Intervention type(s): Drug; Drug; Drug
Intervention description(s): TAK-438 tablets; TAK-438 placebo-matching tablets; Esomeprazole tablets
Intervention MeSH terms: Esomeprazole
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Drug therapy