Safety, Tolerability and Pharmacokinetics of TAK-438 in Healthy Male Participants

Takeda

Status and phase: Completed; Phase 1

Conditions: Ascending Single Dose Study

Treatments: Drug: Placebo; Drug: TAK-438

Study type: Interventional

Funder types: Industry

Identifiers

NCT02123927

TAK-438/CPH-001

U1111-1153-7002 (Other Identifier)

Details and patient eligibility

About

The primary purpose of this study was to evaluate the single dose safety and pharmacokinetics of TAK-438 in healthy 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 and to assess how TAK-438 moves throughout the body. This study will look at lab results and side effects in people who took TAK-438. This study consisted of 2 sequential studies: a single rising dose study (Steps 1 to 7) and a food-effect study (Steps 8 and 9).

The study population for Steps 1 to 7 consisted of 12 participants; with 9 participants randomized to receive a single dose of TAK-438, and 3 participants to receive placebo. Participants in Steps 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, 40, 80, and 120 mg. Steps 8 and 9 consisted of 12 participants in a 2-sequence, 2-period crossover design. Four participants were to receive a single dose of TAK-438 and 2 participants were to receive a single dose of placebo on Day 1, in the fasted state, and 4 participants were to receive a single dose of TAK-438 and 2 participants were to receive a single dose of placebo on Day 1 in the fed state, followed by a second single dose of TAK-438 or placebo in the alternative fed state after a 13 day minimum washout period. Participants in Steps 8 randomized to receive TAK-438 will receive 10 mg and participants in Step 9 will receive 40 mg.

This single-centre trial was conducted in Japan. The overall time to participate in this study was up to 32 days depending on the Step assignment. Participants made 3 to 5 visits to the clinic, including one or two 8-day periods of confinement to the clinic, also depending on Step assignment. All participants made a final visit 15 days after last dose of study drug for a follow-up assessment.

Enrollment: 108 patients

Sex: Male

Ages: 20 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Japanese healthy adult male volunteer.
2. Is between 20 and 45 years old when giving their informed consent.
3. Is able to understand the consents of the study and to follow them.
4. Provides their written informed consent prior to their participation in this study.
5. Weighs at least 50 kg and has a body mass index (BMI) of 18.5 to 25.0 kg/m^2 at screening.
6. Has negative results for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, and serological tests for syphilis.
7. Participant whom the investigator or subinvestigator judged to be eligible on the basis of subjective symptoms, objective findings, vital signs, electrocardiogram (ECG) findings, and results of laboratory tests obtained until before the study drug administration.

Exclusion criteria

1. Has undergone upper gastrointestinal resectioning or vagotomy.
2. Has hypoacidity or anacidity: intragastric pH ≥ 5.5 at X-ray fluoroscopic confirmation of detained position of a pH probe inserted to measure baseline intragastric pH values.
3. Has a history of previous and current acid-related diseases including reflux esophagitis, gastric ulcer, duodenal ulcer, non-erosive gastroesophageal reflux disease, Barrett's esophagitis or Zollinger-Ellison syndrome.
4. Is undergoing H. pylori eradication within 6 months before the initiation of the study drug administration.
5. Has an inappropriate history of previous and current diseases for study participation including hepatic or renal disorders, and cardiovascular, hematological, endocrine, metabolic, pulmonary, gastrointestinal, neurological, urological, immunological, or psychological diseases.
6. Has a history of drug and food allergy.
7. Has a history of illegal drug abuse or alcoholism within 5 years before the initiation of the study drug administration.
8. Has peripheral vessels being difficult.
9. Has undergone whole blood drawing of at least 200 mL within 4 weeks or 400 mL within 12 weeks prior to initiation of the study drug administration.
10. Has undergone whole blood drawing of at least 800 mL in total within 52 weeks prior to initiation of the study drug administration.
11. Has undergone apheresis drawing [plasma (including platelet poor plasma or platelet rich plasma) and platelet component collection] within 2 weeks prior to initiation of the study drug administration.
12. Is taking any prescriptions or over the counter (OTC) drugs within 4 weeks prior to the study drug administration.
13. Has taken any vitamins, herbal medicines, and supplements including St. John's wort, Ginseng, kava kava, ginkgo biloba, melatonin within 4 weeks prior to initiation of the study drug administration.
14. Has had grapefruit (juice and pulp), or caffeine- or alcohol-containing foods or drinks within 72 hr prior to initiation of the study drug administration.
15. Has received other study drugs within 16 weeks prior to initiation of the study drug administration.
16. Participants whom the investigator or subinvestigator judged to be ineligible for study participation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 13 patient groups, including a placebo group

Step 1: TAK-438 1 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-438

Step 2: TAK-438 5 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-438

Step 3: TAK-438 10 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-438

Step 4: TAK-438 20 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-438

Step 5: TAK-438 40 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-438

Step 6: TAK-438 80 mg

Experimental group

Description:

TAK-438 80 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Step 7: TAK-438 120 mg

Experimental group

Description:

TAK-438 120 mg, tablets, orally, once on Day 1.

Treatment:

Drug: TAK-438

Steps 1-7: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Step 8A: TAK-438 10 mg

Experimental group

Description:

TAK-438 10 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 10 mg, tablets, orally, under fed conditions, once on Day 1, Period 2.

Treatment:

Drug: TAK-438

Step 8 B: TAK-438 10 mg

Experimental group

Description:

TAK-438 10 mg, tablets, orally, under fed conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 10 mg, tablets, orally, under fasted conditions, once on Day 1, Period 2.

Treatment:

Drug: TAK-438

Step 9A: TAK-438 40 mg

Experimental group

Description:

TAK-438 40 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 40 mg, tablets, orally, under fed conditions, once on Day 1, Period 2.

Treatment:

Drug: TAK-438

Step 9B: TAK-438 40 mg

Experimental group

Description:

TAK-438 40 mg, tablets, orally, under fed conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 40 mg, tablets, orally, under fasted conditions, once on Day 1, Period 2.

Treatment:

Drug: TAK-438

Steps 8 (A & B) and 9 (A & B): Placebo

Placebo Comparator group

Description:

TAK-438 placebo-matching tablets, orally, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 placebo-matching tablets, orally, once on Day 1, Period 2.

Treatment:

Drug: Placebo