An Open-Label, Single-Dose, Parallel-Group Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 主要终点
- Elimination Rate Constant (Lambda[z])
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics of a single dose of intranasally administered esketamine in participants with impaired renal function when compared to participants with normal renal function.
详细描述
This is an open-label (all people know the identity of the intervention), single-dose, single-center, parallel group study to characterize the pharmacokinetics and safety of a single 28 milligram (mg) dose of esketamine in both participants with varying stages of renal impairment and healthy participants. A total of approximately 32 medically stable men and women with varying degrees of renal function impairment or no renal impairment will be enrolled. The study consists of a Screening period of up to Days -21 to -2, open label phase of Days -1 to 4, and end-of-study (11 plus [+] or minus [-] 2 days after final dose). The participants will be assigned to 1 of 4 groups (8 participants per group) based on creatinine clearance (CLCR,m). Safety and tolerability will be assessed from the time of consent until the end of the study.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
- •For women of childbearing potential, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening; and a negative urine pregnancy test on Day minus (-) 1
- •Comfortable with self-administration of intranasal medication and able to follow instructions provided
- •Hemoglobin concentration of greater than or equal to (>=) 10 grams per deciLiter (g/dL) (Only for cohorts 1, 2, and 3)
- •Platelet count of >= 50,000 counts/microliter (Only for cohorts 1, 2, and 3)
排除标准
- •Current or previous diagnosis of psychotic or major depressive disorder (MDD) with psychosis, bipolar or related disorder, intellectual disability, borderline personality disorder, or antisocial personality disorder
- •A lifetime history of cerebrovascular disease including stroke or transient ischemic attack, aneurysmal vascular disease
- •Unstable coronary artery disease or myocardial infarction in the last 12 months or any unstable angina requiring revascularization procedure, hemodynamically significant valvular heart disease, or New York Heart Association Class III-IV heart failure
- •Has had a renal transplant or diagnosis of systemic lupus erythromatosus or renal carcinoma
- •Has a nasal piercing
- •Participant requires dialysis (Only for cohorts 1, 2, and 3)
研究组 & 干预措施
Cohort 1
Participants with mild renal impairment (Measured Creatinine Clearance [CLCR,m] greater than or equal to >= 50 to 79 milliliter/minute [mL/min]) will self-administer esketamine 28 milligram (mg) intranasally on Day 1.
干预措施: Esketamine (Drug)
Cohort 2
Participants with moderate renal impairment (CLCR,m >=30 to 49 mL/min) will self-administer esketamine 28 mg intranasally on Day 1.
干预措施: Esketamine (Drug)
Cohort 3
Participants with severe renal impairment (CLCR,m less than [<] 30 mL/min), not on dialysis will self-administer esketamine 28 mg intranasally on Day 1.
干预措施: Esketamine (Drug)
Cohort 4
Participants with normal renal function and no evidence of kidney damage (CLCR,m >= 80 mL/min) will self-administer esketamine 28 mg intranasally on Day 1.
干预措施: Esketamine (Drug)
结局指标
主要结局
Elimination Rate Constant (Lambda[z])
时间窗: 60 hours post-dose
Lambda (z) is first-order elimination 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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
时间窗: 60 hours post-dose
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
时间窗: 60 hours post-dose
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 (last) and C(last)/lambda(z); wherein AUC (last) is area under the plasma concentration time curve from time zero to last quantifiable time, C (last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Maximum Observed Plasma Concentration (Cmax)
时间窗: 60 hours post-dose
The Cmax is the maximum observed concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: 60 hours post-dose
The Tmax is defined as actual sampling time to reach maximum observed concentration.
Amount of Drug excreted in Urine (Ae)
时间窗: 60 hours post-dose
Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.
Measured Creatinine Clearance (CLCR,m)
时间窗: 60 hours post-dose
Estimated Creatinine Clearance (CLCR,e)
时间窗: 60 hours post-dose
次要结局
- Number of Participants with Adverse Events(Screening up to End of Follow-up Phase (approximately up to 34 - 38 days))