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

Takeda

Status and phase

Completed

Phase 1

Conditions

Dose Finding Study

Treatments

Drug: TAK-438

Drug: TAK-438 Placebo

Drug: Esomeprazole

Study type

Interventional

Funder types

Industry

Identifiers

NCT02141698

U1111-1153-8406 (Other Identifier)

TAK-438_101

2007-003616-66 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

73 patients

Sex

Male

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Single Group Assignment

Masking

Quadruple Blind

73 participants in 15 patient groups, including a placebo group

Cohort 1: TAK-438 1 mg

Experimental group

Description:

TAK-438 1 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 2: TAK-438 5 mg

Experimental group

Description:

TAK-438 5 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 3: TAK-438 10 mg

Experimental group

Description:

TAK-438 10 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 4: TAK-438 20 mg

Experimental group

Description:

TAK-438 20 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 5: TAK-438 15 mg

Experimental group

Description:

TAK-438 15 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 6: TAK-438 40 mg

Experimental group

Description:

TAK-438 40 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 7: TAK-438 30 mg

Experimental group

Description:

TAK-438 30 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Cohort 8A: Food-effect

Experimental group

Description:

TAK-438 20 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 2.

Treatment:

Drug: TAK-438

Cohort 8B: Food-effect

Experimental group

Description:

TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 1.

Treatment:

Drug: TAK-438

Cohort 9: TAK-438 Multiple Dose 1

Experimental group

Description:

TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7.

Treatment:

Drug: TAK-438

Cohort 10: TAK-438 Multiple Dose 2

Experimental group

Description:

TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7.

Treatment:

Drug: TAK-438

Cohort 11: TAK-438 Multiple Dose 3

Experimental group

Description:

TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7.

Treatment:

Drug: TAK-438

Cohort 12: Ethnic Bridging

Experimental group

Description:

TAK-438 tablets, dose 1, orally, on Days 1-7 of Period 1, followed by a 4-week washout period followed by TAK-438 tablets, dose 2, orally, Days 1-7 of Period 2, followed by a 4-week washout period, followed by esomeprazole tablets, 40 mg, orally, on Days 1-7 of Period 3. TAK-438 doses to be determined from data collected in Cohorts 9-11.

Treatment:

Drug: Esomeprazole

Drug: TAK-438

Cohorts 1-7: Placebo

Placebo Comparator group

Description:

TAK-438 placebo-matching tablets, orally, once on Day 1

Treatment:

Drug: TAK-438 Placebo

Cohorts 9-11: Placebo

Placebo Comparator group

Description: