A Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Renal Impairment, Healthy

Intervention / Treatment
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* Drug: Esketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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. | Drug: Esketamine<br>* Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.<br>* Other names: JNJ-54135419;|
| Experimental: Cohort 2<br>Participants with moderate renal impairment (CLCR,m >=30 to 49 mL/min) will self-administer esketamine 28 mg intranasally on Day 1. | Drug: Esketamine<br>* Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.<br>* Other names: JNJ-54135419;|
| Experimental: Cohort 3<br>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. | Drug: Esketamine<br>* Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.<br>* Other names: JNJ-54135419;|
| Experimental: Cohort 4<br>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. | Drug: Esketamine<br>* Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.<br>* Other names: JNJ-54135419;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | The Cmax is the maximum observed concentration. | 60 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | The Tmax is defined as actual sampling time to reach maximum observed concentration. | 60 hours post-dose | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) | The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. | 60 hours post-dose | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) | 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. | 60 hours post-dose | 
| Elimination Rate Constant (Lambda[z]) | 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. | 60 hours post-dose | 
| Amount of Drug excreted in Urine (Ae) | Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals. | 60 hours post-dose | 
| Measured Creatinine Clearance (CLCR,m) |  | 60 hours post-dose | 
| Estimated Creatinine Clearance (CLCR,e) |  | 60 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Screening up to End of Follow-up Phase (approximately up to 34 - 38 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Impairment, Healthy, Esketamine