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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02606084
• Other study ID #: CR108058
• Secondary ID: 54135419TRD1014
• Status: Completed
• Phase: Phase 1
• Start date: December 4, 2015
• Est. completion date: February 2, 2018

Study information

• Verified date: March 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 2, 2018
• Est. primary completion date: February 2, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Esketamine
Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)	The Cmax is the maximum observed concentration.	60 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Measured Creatinine Clearance (CLCR,m)		60 hours post-dose
Primary	Estimated Creatinine Clearance (CLCR,e)		60 hours post-dose
Secondary	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)

External Links

•   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