One-centre Safety and Pharmacokinetics Phase I Study of Inhaled Esketamine in Healthy Volunteers With Two Single Ascending Dose and One Double-blind Multiple Ascending Dose Parts
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Number of inhalations needed to achieve the assumed Esketamine antidepressive plasma concentration.
研究概览
简要总结
The planned study is to determine the pharmacokinetic properties of Esketamine and safety assessment with inhaled Esketamine after different number of inhalations and different dosing sequences within three parts of the study.
详细描述
This is to be one-centre, single ascending dose and double-blind placebo controlled multiple dose three part study of Esketamine DPI (dry powder inhaler) in healthy volunteers.
PART A is a single dose, open-label part with Esketamine DPI inhalations administered with dose escalation between cohorts.
PART B is a single dose, open-label part with Esketamine DPI inhalations administered in different dosing sequences with dose escalation between cohorts.
PART C is a multiple dose, double-blind, placebo-controlled part with Esketamine DPI inhalations administered in different cycles of treatment (with four dosing sequences within two weeks) with dose escalation between cohorts. Participants in this part will be randomized to receive Esketamine DPI or placebo in 3:1 ratio.
Pharmacokinetic properties and safety of Esketamine DPI will be determined following different number of inhalations in PART A, different dosing sequences in PART B and different cycles of treatment in PART C.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Only PART C will be double-blind.
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
- •Caucasian female or male,
- •Age: 18-55 years old, inclusive,
- •Body-mass index (BMI): ≥18.5 kg/m^2 and <29.9 kg/m^2
- •Non-smoker and nonuser of tobacco products for at least 1 year before screening,
- •Physical examination without any clinically relevant abnormality,
- •Laboratory values not clinically significant,
- •Volunteer (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception.
排除标准
- •Known allergy or hypersensitivity to ketamine or its derivates and/or to any study product excipients,
- •Any known significant current or past acute or chronic disease or condition,
- •Participation in other clinical trial within 90 days preceding the screening,
- •Blood drawn within 30 days prior to inclusion to the study (more or equal to 300mL),
- •Positive results from pregnancy test for female participants,
- •Lactation in women participants,
- •Hypotension or hypertension in medical history,
- •Narcotic, alcohol addiction or abuse,
- •Participant who adhere to a special diet (e.g. low calories, vegetarian).
研究组 & 干预措施
PART A
6 cohorts will receive single dose of Esketamine DPI administered with dose escalation between cohorts.
干预措施: Esketamine DPI (Drug)
PART B
4 cohorts will receive single dose of Esketamine DPI administered with dose escalation between cohorts.
干预措施: Esketamine DPI (Drug)
PART C
4 cohorts will receive multiple dose of Esketamine DPI in two weeks' time administered with dose escalation between cohorts.
干预措施: Esketamine DPI (Drug)
PART C placebo
4 cohorts will receive multiple dose of matching placebo in two weeks' time.
干预措施: Placebo DPI (Drug)
结局指标
主要结局
Number of inhalations needed to achieve the assumed Esketamine antidepressive plasma concentration.
时间窗: up to 24 hours after study drug administration in PART A
Number of inhalations within dosing sequence needed to maintain the assumed Esketamine antidepressive plasma concentration.
时间窗: up to 24 hours after study drug administration in PART B
Cmax - maximum Esketamine plasma concentration
时间窗: up to 24 hours after each study drug administration in PART A, B and C of the study.
The maximum concentration of the Esketamine in plasma after drug administration, obtained directly from the measured concentrations.
AUC (0-24) - area under the Esketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration
时间窗: up to 24 hours after each study drug administration in PART A, B and C of the study.
The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after study drug administration.
次要结局
- Kel -elimination rate constant(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- Cmax - maximum Esnorketamine plasma concentration(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- Tmax - time to reach maximum Esketamine plasma concentration(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- AUC (0-24) - area under the Esnorketamine plasma concentration-time curve from time 0 to 24 hours after study drug administration.(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- Tmax - time to reach maximum Esnorketamine plasma concentration.(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- AUC (0-inf) - area under the Esketamine plasma concentration-time curve from time 0 to infinity time(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- T1/2 - plasma elimination half-life for Esketamine(up to 24 hours after each study drug administration in PART A, B and C of the study.)
- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs).(up to 7 days in PART A and PART B of the study and up to 25 days in PART C of the study.)