A Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 主要终点
- Maximum plasma concentration during a dosing interval (Cmax) of esketamine
研究概览
简要总结
The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to the medication) of intranasally (through the nose) administered esketamine in healthy participants.
详细描述
This is a single-center study with 3 cohorts (groups). Approximately 58 participants will be enrolled in this study. In Cohort 1, approximately 16 participants will be enrolled for up to 78 days and they will receive 4 different single-dose regimens (Treatment A, B, C and D) of intranasal spray of esketamine solution in a crossover manner (participants will be switched from one single-dose regimen to another) and in an open label manner (both the investigator and the participant know the intervention received by the participant). In Cohort 2, approximately 14 participants will be enrolled for up to 35 days and they will receive 1 regimen of intranasal esketamine (Treatment D) in an open label manner. In Cohort 3, approximately 28 participants will be enrolled and they will be randomly assigned to receive either Treatment E (intranasal esketamine spray) or Treatment F (intranasal placebo spray) in a double blind manner (both the investigator and the participant do not know the intervention received by the participant). Safety evaluations will include assessment of adverse events, targeted nasal examinations, laboratory tests, electrocardiogram, physical examination, pulse oximetery, and vital signs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Blood pressure between 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic
- •A 12-lead electrocardiogram consistent with normal cardiac conduction and function
- •Agree to protocol-defined method of contraception
- •Comfortable with self-administration of intranasal medication
排除标准
- •History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease; hematologic disease; coagulation disorders; significant pulmonary disease, including bronchospastic respiratory disease; diabetes mellitus; renal or hepatic insufficiency; thyroid disease; neurologic or psychiatric disease, asthma
- •Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center
- •Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram at screening or at admission to the study center
- •Known allergy to heparin or history of heparin-induced thrombocytopenia
研究组 & 干预措施
Cohort 1: Treatment A
Participants will receive 1 spray of esketamine solution in each nostril once (total dose: 28 mg).
干预措施: Esketamine (Drug)
Cohort 1: Treatment B
Participants will receive 1 spray of esketamine solution in each nostril twice, with 5 minutes interval (total dose: 56 mg).
干预措施: Esketamine (Drug)
Cohort 1: Treatment C
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 5 minutes interval between each repeated sprays (total dose 84 mg).
干预措施: Esketamine (Drug)
Cohort 1: Treatment D
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 10 minutes interval between each repeated sprays (total dose 84 mg).
干预措施: Esketamine (Drug)
Cohort 2: Treatment D
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 10 minutes interval between each repeated sprays (total dose 84 mg).
干预措施: Esketamine (Drug)
Cohort 3: Treatment E
Participants will receive 1 spray of esketamine solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution.
干预措施: Esketamine (Drug)
Cohort 3: Treatment E
Participants will receive 1 spray of esketamine solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution.
干预措施: Placebo (Drug)
Cohort 3: Treatment F
Participants will receive 1 spray of placebo solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single 0.25-mg oral dose of triazolam will be administered 5 minutes before the first intranasal spray of placebo solution.
干预措施: Placebo (Drug)
Cohort 3: Treatment F
Participants will receive 1 spray of placebo solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single 0.25-mg oral dose of triazolam will be administered 5 minutes before the first intranasal spray of placebo solution.
干预措施: Triazolam (Drug)
结局指标
主要结局
Maximum plasma concentration during a dosing interval (Cmax) of esketamine
时间窗: Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours
Time to reach the maximum plasma concentration (tmax) of esketamine
时间窗: Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours
Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of esketamine
时间窗: Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours
次要结局
- Number of participants with adverse events(Up to 78 days)