A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Single and Multiple Oral Dose of TAK-418 in Healthy Female Participants

Millennium Pharmaceuticals

Status and phase: Terminated; Phase 1

Conditions: Healthy Volunteers

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03501069

U1111-1209-4647 (Other Identifier)

TAK-418-1003

Details and patient eligibility

About

The purpose of this study is to characterize safety and tolerability of TAK-418 in non-Japanese and Japanese healthy female participants when administered at single or multiple (once daily [QD]) oral doses.

Full description

The drug being tested in this study is called TAK-418. This study will assess the safety, tolerability, PK and PD of single and multiple rising doses of TAK-418 in healthy Japanese or non-Japanese females.

The study will enroll approximately 48 participants in 6 cohorts and each cohort will have 8 participants. The study will include 2 parts: single rising dose (SRD) in Cohort 1 and multiple rising dose (MRD) in Cohorts 2 to 6. Cohort 3 will include cerebrospinal fluid (CSF) collection. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 6 cohorts.

This two-center trial will be conducted in the United States. The overall time to participate in Cohort 1 of this study is approximately 105 days and 98 days in Cohort 2. Participants will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Enrollment: 32 patients

Sex: Female

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Has a body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the Screening Visit. (Cohorts 1 to 4 only).
2. Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the first dose of trial drug or invasive procedure.
3. The participant either is of nonchildbearing potential, OR, if of childbearing potential, is using a highly effective method of contraception with low user dependency during the entire duration of the study.

For Cohorts 5 and 6 (Japanese participants) only:

1. Has a BMI >=18.0 and <= 26.0 kg/m^2, at the Screening Visit.

Exclusion criteria

1. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody/antigen, at Screening.
2. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.
3. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).
4. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
5. Has a substance abuse disorder.
6. Has risk of suicide according to the investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the 6 months before Screening.
7. Has luteinizing hormone (LH), follicle-stimulating hormone (FSH), or estradiol levels that are clinically abnormal.
8. Has a resting heart rate outside of the range of 50 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).

For Cohort 3 only (includes CSF sample collection):

1. Has had CSF collection performed within 30 days before Check-in (Day -1).
2. Has significant vertebral deformities (scoliosis or kyphosis) that, in the opinion of the investigator, may interfere with the lumbar puncture procedure.
3. Has a local infection at the puncture site.
4. Has thrombocytopenia or other suspected bleeding tendencies noted before the procedure.
5. Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia.
6. Has any focal neurological deficit that might suggest an increase in intracranial pressure.
7. Has any abnormal finding on ophthalmological assessment/fundoscopy indicative of raised intracranial pressure (that is, optic disc swelling/edema; or [uncontrolled] hypertensive retinopathy).
8. Regularly has moderate-to-severe headaches requiring analgesics.
9. Has any bleeding abnormality or history of bleeding abnormalities.
10. Has abnormal coagulation tests (prothrombin time [PT]/international normalized ratio [INR], partial thromboplastin time [PTT]) at Screening.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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32 participants in 6 patient groups

Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg

Experimental group

Description:

TAK-418 120 milligram (mg) or TAK-418 matching placebo, capsule, orally, once on Day 1 of Period A followed by a minimum of 14 days of washout period, followed by TAK-418 160 mg or TAK-418 matching placebo, capsule, orally, once on Day 1 of Period B. The actual TAK-418 dose for Period B will be determined based on safety, tolerability, and PK data available from the previous dose in Period A.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418

Non-Japanese Cohort 2: TAK-418 20 mg

Experimental group

Description:

TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418

Non-Japanese Cohort 3: TAK-418 40 mg

Experimental group

Description:

TAK-418 40 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 3 will be determined based on safety, tolerability, and PK data available from the previous doses.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418

Non-Japanese Cohort 4: TAK-418 60 mg

Experimental group

Description:

TAK-418 60 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 4 will be determined based on safety, tolerability, and PK data available from the previous doses.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418

Japanese Cohort 5: TAK-418 20 mg

Experimental group

Description:

TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 5 will be determined based on safety, tolerability, and PK data available from the previous doses.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418

Japanese Cohort 6: TAK-418 40 mg

Experimental group

Description:

TAK-418 40 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days. The actual TAK-418 dose for Cohort 6 will be determined based on safety, tolerability, and PK data available from the previous doses.

Treatment:

Drug: TAK-418 Matching Placebo

Drug: TAK-418