Back to resultsA Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine
Primary Purpose
Renal Impairment, Healthy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Esketamine
Sponsored by
About this trial
This is an interventional treatment trial for Renal Impairment focused on measuring Renal Impairment, Healthy, Esketamine
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
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.
Participants with moderate renal impairment (CLCR,m >=30 to 49 mL/min) will self-administer esketamine 28 mg intranasally on Day 1.
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.
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.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax)
The Cmax is the maximum observed concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
The Tmax is defined as actual sampling time to reach maximum observed concentration.
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.
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.
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.
Amount of Drug excreted in Urine (Ae)
Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.
Measured Creatinine Clearance (CLCR,m)
Estimated Creatinine Clearance (CLCR,e)
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT02606084
First Posted
November 13, 2015
Last Updated
March 27, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02606084
Brief Title
A Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
December 4, 2015 (Actual)
Primary Completion Date
February 2, 2018 (Actual)
Study Completion Date
February 2, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment, Healthy
Keywords
Renal Impairment, Healthy, Esketamine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants with moderate renal impairment (CLCR,m >=30 to 49 mL/min) will self-administer esketamine 28 mg intranasally on Day 1.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Other Intervention Name(s)
JNJ-54135419
Intervention Description
Participants will self-administer esketamine solution intranasally 28 milligram (mg) on Day 1.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Description
The Cmax is the maximum observed concentration.
Time Frame
60 hours post-dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description
The Tmax is defined as actual sampling time to reach maximum observed concentration.
Time Frame
60 hours post-dose
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
Description
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time Frame
60 hours post-dose
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Description
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.
Time Frame
60 hours post-dose
Title
Elimination Rate Constant (Lambda[z])
Description
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.
Time Frame
60 hours post-dose
Title
Amount of Drug excreted in Urine (Ae)
Description
Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.
Time Frame
60 hours post-dose
Title
Measured Creatinine Clearance (CLCR,m)
Time Frame
60 hours post-dose
Title
Estimated Creatinine Clearance (CLCR,e)
Time Frame
60 hours post-dose
Secondary Outcome Measure Information:
Title
Number of Participants with Adverse Events
Description
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.
Time Frame
Screening up to End of Follow-up Phase (approximately up to 34 - 38 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Miami
State/Province
Florida
Country
United States
City
Knoxville
State/Province
Tennessee
Country
United States
12. IPD Sharing Statement
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108058&attachmentIdentifier=f5911918-6048-4dec-8e77-5fc22104b6ae&fileName=CR108058_CSR.pdf&versionIdentifier=
Description
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
Learn more about this trial
A Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine
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