A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-418 in Healthy Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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).
- •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.
- •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:
- •Has a BMI >=18.0 and <= 26.0 kg/m^2, at the Screening Visit.
排除标准
- •Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody/antigen, at Screening.
- •Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.
- •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).
- •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.
- •Has a substance abuse disorder.
- •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.
- •Has luteinizing hormone (LH), follicle-stimulating hormone (FSH), or estradiol levels that are clinically abnormal.
- •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):
- •Has had CSF collection performed within 30 days before Check-in (Day -1).
- •Has significant vertebral deformities (scoliosis or kyphosis) that, in the opinion of the investigator, may interfere with the lumbar puncture procedure.
- •Has a local infection at the puncture site.
- •Has thrombocytopenia or other suspected bleeding tendencies noted before the procedure.
- •Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia.
- •Has any focal neurological deficit that might suggest an increase in intracranial pressure.
- •Has any abnormal finding on ophthalmological assessment/fundoscopy indicative of raised intracranial pressure (that is, optic disc swelling/edema; or [uncontrolled] hypertensive retinopathy).
- •Regularly has moderate-to-severe headaches requiring analgesics.
- •Has any bleeding abnormality or history of bleeding abnormalities.
- •Has abnormal coagulation tests (prothrombin time [PT]/international normalized ratio [INR], partial thromboplastin time [PTT]) at Screening.
研究组 & 干预措施
Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg
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.
干预措施: TAK-418 (Drug)
Non-Japanese Cohort 1: TAK-418 120 mg and TAK-418 160 mg
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.
干预措施: TAK-418 Matching Placebo (Drug)
Non-Japanese Cohort 2: TAK-418 20 mg
TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days.
干预措施: TAK-418 (Drug)
Non-Japanese Cohort 2: TAK-418 20 mg
TAK-418 20 mg or TAK-418 matching placebo, capsule, orally, once daily for 10 days.
干预措施: TAK-418 Matching Placebo (Drug)
Non-Japanese Cohort 3: TAK-418 40 mg
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.
干预措施: TAK-418 (Drug)
Non-Japanese Cohort 3: TAK-418 40 mg
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.
干预措施: TAK-418 Matching Placebo (Drug)
Non-Japanese Cohort 4: TAK-418 60 mg
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.
干预措施: TAK-418 (Drug)
Non-Japanese Cohort 4: TAK-418 60 mg
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.
干预措施: TAK-418 Matching Placebo (Drug)
Japanese Cohort 5: TAK-418 20 mg
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.
干预措施: TAK-418 (Drug)
Japanese Cohort 5: TAK-418 20 mg
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.
干预措施: TAK-418 Matching Placebo (Drug)
Japanese Cohort 6: TAK-418 40 mg
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.
干预措施: TAK-418 (Drug)
Japanese Cohort 6: TAK-418 40 mg
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.
干预措施: TAK-418 Matching Placebo (Drug)
结局指标
主要结局
Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose
时间窗: Baseline up to Day 70
Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
时间窗: Baseline up to Day 60
Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose
时间窗: Baseline up to Day 70
Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE)
时间窗: Baseline up to Day 60
Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose
时间窗: Baseline up to Day 60
Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose
时间窗: Baseline up to Day 60
Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose
时间窗: Baseline up to Day 70
Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE
时间窗: Baseline up to Day 70
次要结局
- Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1(Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10(Days 1 and 10 pre-dose and at multiple time points (up to 24 hours) post-dose)
- Cmax: Maximum Observed Plasma Concentration for TAK-418(Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose)
- Tmax: Time to Reach the Cmax for TAK-418(Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose)