A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Oral Single Dose of TAK-418 in Healthy Participants

Takeda

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: TAK-418 Placebo; Drug: TAK-418

Study type: Interventional

Funder types: Industry

Identifiers

NCT03228433

TAK-418-1001

U1111-1195-7777 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants.

Full description

The drug being tested in this study is called TAK-418. TAK-418 is being tested in healthy participants in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of single oral doses.

The study will enroll approximately 40 healthy participants. The study consists of equally divided 5 sequential cohorts of 8 participants each. In each of the following cohorts, 6 participants will be randomized to receive TAK-418 and 2 participants will receive matching placebo-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Cohort 1: TAK-418 5 mg
• Cohort 2: TAK-418 15 mg
• Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed
• Cohort 4: TAK-418 40 mg
• Cohort 5: TAK-418 60 mg

All participants will be asked to take TAK-418 or placebo-matching capsule once on Day 1 in each cohort. A washout period of 28-days will be maintained between the doses in Cohort 3.

This single center trial will be conducted in the United States. Participants in this study will be assigned to one of 5 possible dose cohorts. Male participants will return for additional outpatient visits on Days 91 and 93 (+/- 7 days) and may return for outpatient visits on Days 182 and 184 (+/- 7 days) (depending on results from the Day 93 Visit).

Enrollment: 40 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Is a male or female participants with a body mass index (BMI) within the range of 18.5 -30.0 kilogram per square meter (kg/m^2) at the Screening Visit.

2. Is a nonsmoker who has not used tobacco or nicotine-containing products (example, nicotine patch) for at least 6 months before trial drug administration of the initial dose of trial drug or invasive procedure.

3. Must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the Screening Visit and before administration of the initial dose of trial drug or invasive procedure as per principal investigator's judgment.

4. Female subjects with no childbearing potential, defined by at least 1 of the following criteria:

   • Postmenopausal (defined as 12 months of spontaneous amenorrhea in women aged greater than [>]45 years, 6 months of spontaneous amenorrhea in women aged >45 years with serum follicle-stimulating hormone [FSH] levels >40 milli-international units per milliliter [mIU/mL]). Appropriate documentation of FSH levels is required.
   • Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure.
   • Had a tubal ligation with appropriate documentation of surgical procedure.
   • Has a congenital condition resulting in no uterus.

Exclusion criteria

1. Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.
2. Has a risk of suicide according to the investigator's clinical judgment per the Columbia-Suicide Severity Rating Scale at Screening or has made a suicide attempt in the 6 months before Screening.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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40 participants in 6 patient groups, including a placebo group

Cohort 1: TAK-418 5 mg

Experimental group

Description:

TAK-418 5 milligram (mg), capsule, orally, once on Day 1.

Treatment:

Drug: TAK-418

Cohort 2: TAK-418 15 mg

Experimental group

Description:

TAK-418 15 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.

Treatment:

Drug: TAK-418

Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed

Experimental group

Description:

TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.

Treatment:

Drug: TAK-418

Cohort 4: TAK-418 40 mg

Experimental group

Description:

TAK-418 40 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.

Treatment:

Drug: TAK-418

Cohort 5: TAK-418 60 mg

Experimental group

Description:

TAK-418 60 mg, capsule, orally, once on Day 1. Actual dose of TAK-418 may vary based on safety, tolerability and PK data from previous Cohorts.

Treatment:

Drug: TAK-418

Cohorts 1-5: Placebo

Placebo Comparator group

Description:

TAK-418 placebo-matching, capsule, orally, once on Day 1.

Treatment:

Drug: TAK-418 Placebo