Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide.
研究概览
简要总结
- Cohort 1: To evaluate the drug interactions, safety, and tolerability of oral edaravone when coadministered with rosuvastatin, sildenafil or furosemide in healthy adult males
- Cohort 2: To evaluate the pharmacokinetics, safety, and tolerability of oral edaravone in healthy Japanese and Caucasian adult males
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy adult male volunteers
- •Cohort 1: Japanese, Cohort 2: Japanese or Caucasian
- •Subjects aged between 20 and 45 years at the time of informed consent
- •Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study
排除标准
- •Additional screening criteria check may apply for qualification:
- •Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study
- •Body mass index (BMI) of <18.0 or >30.0, or body weight of <50 kg (BMI formula: body weight [kg]/height [m]2, rounded to one decimal place)
- •Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs
- •Subjects who do not agree to use an effective method of contraception from initiation of study drug administration to 14 days after completion (discontinuation) of study drug administration
- •Subjects who have previously received edaravone
- •Subjects who have participated in another clinical study and received a study drug within 12 weeks before providing informed consent
- •Use of any drug(s) other than the study drug or as-needed use of acetylsalicylic acid within 7 days before the initiation of study drug or victim drug administration
- •Use of any alcohol, xanthine, or caffeine-containing product(s) within 24 hours before screening and Day -1 visiting
- •Use of any supplement(s) within 7 days before the initiation of study drug or victim drug administration
- •Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances during the following periods (Cohort 1: within 7 days before the initiation of victim drug administration, Cohort 2: within 24 hours before each Day -1 visiting)
- •Use of any tobacco or nicotine-containing product(s) (Cohort 1: within 12 weeks before the initiation of victim drug administration during the following periods, Cohort 2: within 24 hours before each Day -1 visiting)
- •Use of any health food(s) containing St John's Wort (Hypericum perforatum) within 2 weeks before the initiation of victim drug administration (only in Cohort 1)
研究组 & 干预措施
Rosuvastatin, Sildenafil, and MT-1186
Group 1 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.
干预措施: MT-1186 (Drug)
Furosemide and MT-1186
Group 2 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.
干预措施: MT-1186 (Drug)
Rosuvastatin, Sildenafil, and MT-1186
Group 1 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.
干预措施: Sildenafil (Drug)
Furosemide and MT-1186
Group 2 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.
干预措施: Furosemide (Drug)
MT-1186
Cohort 2:
A three-way crossover study in which Japanese healthy male subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Caucasian healthy male subjects receive a single dose of MT-1186 at the same period with Japanese subjects under the corresponding condition on Day 1, 4, or 7 according to their treatment schedule.
干预措施: MT-1186 (Drug)
Rosuvastatin, Sildenafil, and MT-1186
Group 1 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.
干预措施: Rosuvastatin (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide.
时间窗: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide.
时间窗: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
Tmax of Rosuvastatin, Sildenafil and Furosemide.
时间窗: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
T1/2 of Rosuvastatin, Sildenafil and Furosemide.
时间窗: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
AUC0-inf of Unchanged Edaravone.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Cmax of Unchanged Edaravone.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Tmax of Unchanged Edaravone.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Unchanged Edaravone.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
AUC0-inf of Sulfate Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Sulfate Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Sulfate Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Sulfate Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
AUC0-inf of Glucuronide Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Glucuronide Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Glucuronide Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Glucuronide Conjugate.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
AUCinf of Sulfate Conjugate and Glucuronide Conjugate.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Cmax of Sulfate Conjugate and Glucuronide Conjugate.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Tmax of Sulfate Conjugate and Glucuronide Conjugate.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Sulfate Conjugate and Glucuronide Conjugate.
时间窗: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Number of Participants With Adverse Events and Adverse Drug Reactions
时间窗: Day 1 to 20 in group 1 of cohort 1, Day 1 to 14 in group 2 of cohort 1, Day 1 to 14 of cohort 2
AUC0-inf of Unchanged Edaravone.
时间窗: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Unchanged Edaravone.
时间窗: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Unchanged Edaravone.
时间窗: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Unchanged Edaravone.
时间窗: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Glucuronide Conjugate.
时间窗: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
次要结局
- Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.(Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose)
- Tmax of Unchanged Edaravone.(Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose)
- AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.(Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose)
- T1/2 of Unchanged Edaravone.(Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose)