An Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Han Chinese, Korean, Japanese, and Caucasian Subjects and the Effects of Rifampin on the Pharmacokinetics of Intranasally Administered Esketamine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics of intranasally administered esketamine in healthy Han Chinese, Korean, Japanese, and Caucasian participants and to evaluate the effects of rifampin on the pharmacokinetics of intranasally administered esketamine in healthy Caucasian participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Cohort 1: healthy Han Chinese participants 20 to 55 years of age, inclusive, who have resided outside of China for no more than 10 years and have parents and maternal and paternal grandparents who are of Han Chinese ethnicity For Cohort 2: healthy Korean participants 20 to 55 years of age, inclusive, who have resided outside of Korea for no more than 10 years and have parents and maternal and paternal grandparents who are of Korean ethnicity For Cohort 3: healthy Japanese participants 20 to 55 years of age, inclusive, who have resided outside of Japan for no more than 10 years and have parents and maternal and paternal grandparents who are of Japanese ethnicity For Cohort 4: healthy Caucasian participants 20 to 55 years of age, inclusive Participants must be within +/-7 years and +/-20 percent (%) of the combined mean age and mean body weight at Screening, respectively, of Cohort 1, Cohort 2, and Cohort 3
- •Body mass index (BMI; weight [kilogram]/height^2 [m]^2) between 18 and 30 kilogram per meter square (kg/m^2), inclusive, and a body weight not less than 47 kilogram (kg)
- •If a woman, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening
- •If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 1 month after receiving the last dose of study drug
- •Creatinine clearance more than equal to (>=)80 milliliters per minute (mL/min) based on Cockroft-Gault equation
排除标准
- •Current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
- •Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
- •Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
- •History of drug or alcohol abuse disorder within the past 1 year, or a reason to believe a participant has such a history
- •Regular use of intranasal tobacco powder within the past 1 year, or a reason to believe a participant has such a history
研究组 & 干预措施
Esketamine
Participants in Cohort 1 (Han Chinese participants), Cohort 2 (Korean participants) and Cohort 3 (Japanese participants ) will receive 100-microliter (mcL) spray of 14 percent (%) esketamine solution (14 milligram [mg]) into each nostril at Time 0 and 5 minutes later for a total dose of 56 milligram (mg) in Period 1.
干预措施: Esketamine (Drug)
Esketamine+Rifampin
Participants in Cohort 4 (Caucasian participants) will receive a 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 1 followed by rifampin from Day -6 to Day -1 of treatment Period 2 and followed by 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 2.
干预措施: Esketamine (Drug)
Esketamine+Rifampin
Participants in Cohort 4 (Caucasian participants) will receive a 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 1 followed by rifampin from Day -6 to Day -1 of treatment Period 2 and followed by 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 2.
干预措施: Rifampin (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Up to Day 2
The Cmax is the maximum observed plasma concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: Up to Day 2
The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Time to Last Observed Quantifiable Plasma Concentration (Tlast)
时间窗: Up to Day 2
The Tlast is the time to last observed quantifiable plasma concentration.
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC12h)
时间窗: Up to Day 2
The (AUC12h) is the area under the plasma concentration-time curve from time 0 to 12 hours Post-dose.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last)
时间窗: Up to Day 2
The AUC (0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
时间窗: Up to Day 2
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
Elimination Half-life (t1/2)
时间窗: Up to Day 2
Elimination half-life (t \[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Rate Constant (Lambda[z])
时间窗: Up to Day 2
Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
次要结局
- Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability(Up to Follow-up (45 days))