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

January 31, 2025 updated by: Janssen Research & Development, LLC

An Open-Label, Single-Dose, Parallel-Group Study to Assess the Effects of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine

The purpose of this study is to evaluate the pharmacokinetics, safety, and tolerability of intranasally administered esketamine in both participants with varying stages of hepatic impairment and healthy participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a parallel group, single-center, single-dose, open-label (all people know the identity of the intervention), study to assess the pharmacokinetics and safety of a single 28 milligram (mg) dose of esketamine in both participants with varying stages of hepatic impairment and healthy participants. The participants will be assigned to 1 of 3 groups (8 participants per group) based on hepatic impairment which will be classified during Screening. Cohort 1 (participants with moderate hepatic impairment), Cohort 2 (participants with mild hepatic impairment), and Cohort 3 (participants with normal hepatic function and no evidence of liver damage). Participants will self-administer a single dose of intranasal Esketamine 28 mg. The total duration of the study from Screening through Follow-up, is approximately 34 to 38 days. Blood and urine samples for assessment of Esketamine pharmacokinetics will be collected for up to 60 hours after study drug administration. Participants' safety will be monitored throughout the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Cohorts 1, 2 and 3 (All participants):

  • Body mass index (BMI) between 18 and 34 kilogram (kg)/meter square ([m]^2) (inclusive), and body weight not less than 50 kilogram (kg)
  • Creatinine clearance of greater than or equal to (> =) 60 milliliter per minute (mL/min) based on the Cockcroft-Gault equation
  • 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

Cohorts 1 and 2 (Participants with Hepatic impairment):

  • A total Child-Pugh score of 5 or 6 for participants with mild impairment and between 7 and 9 (inclusive) for participants with moderate impairment
  • Participants must have stable hepatic function and consistent classification (mild or moderate hepatic impairment) between Screening and Day -1

Exclusion Criteria:

Cohorts 1, 2 and 3 (All participants):

  • Participants of Asian origin
  • Diagnosed with a current or previous psychotic or major depressive disorder (MDD) with psychosis, bipolar or related disorder, intellectual disability, borderline personality disorder, or antisocial personality disorder

Cohorts 1 and 2 (Participants with Hepatic impairment):

  • History of hepatopulmonary syndrome, hydrothorax or hepatorenal syndrome
  • Positive test for alcohol or drugs of abuse per local standard practices

Cohorts 3 (Healthy participants):

  • Clinically significant medical illness
  • Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator
  • Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies at Screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Participants with moderate hepatic impairment will receive esketamine solution (containing 14 milligram [mg] of esketamine base per 100 microliter [mcl]) by intranasal route into each nostril using nasal spray pump at 0 hour (h) on Day 1.
Drug: Esketamine
Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.
Other Names:
  • JNJ-54135419
Experimental: Cohort 2
Participants with mild hepatic impairment will receive esketamine solution (containing 14 mg of esketamine base per 100 mcl) by intranasal route into each nostril using nasal spray pump at 0h on Day 1.
Drug: Esketamine
Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.
Other Names:
  • JNJ-54135419
Experimental: Cohort 3
Participants with normal hepatic function and no evidence of liver damage will receive esketamine solution (containing 14 mg of esketamine base per 100 mcl) by intranasal route into each nostril using nasal spray pump at 0h on Day 1.
Drug: Esketamine
Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.
Other Names:
  • JNJ-54135419

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration (Cmax)
Time Frame: up to 60 hours after study drug administration
The Cmax is the maximum plasma concentration.
up to 60 hours after study drug administration
Time to Reach Maximum Concentration (tmax)
Time Frame: up to 60 hours after study drug administration
Time to reach the maximum observed plasma concentration.
up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last (AUC [0-last])
Time Frame: up to 60 hours after study drug administration
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable 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; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Time Frame: up to 60 hours after study drug administration
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; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
up to 60 hours after study drug administration
Elimination Half-life period (t1/2) Associated with the Terminal Slope (Lambda z)
Time Frame: up to 60 hours after study drug administration
Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours (AUC [0-12])
Time Frame: up to 12 hours after study drug administration
The AUC (0-12) is the area under the plasma concentration-time curve from time 0 to 12 hours post-dose.
up to 12 hours after study drug administration
Rate Constant (Lambda[z])
Time Frame: up to 60 hours after study drug administration
Lambda(z) is first-order 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.
up to 60 hours after study drug administration
Cmax Metabolite to Parent Ratio (MPR Cmax)
Time Frame: up to 60 hours after study drug administration
Cmax metabolite to parent ratio, and corrected for molecular weight if necessary.
up to 60 hours after study drug administration
AUC(last) Metabolite to Parent Ratio (MPR AUC[last])
Time Frame: up to 60 hours after study drug administration
AUC(last) metabolite to parent ratio, and corrected for molecular weight if necessary.
up to 60 hours after study drug administration
AUC (infinity) Metabolite to Parent Ratio (MPR AUC [infinity])
Time Frame: up to 60 hours after study drug administration
AUC (infinity) metabolite to parent ratio, and corrected for molecular weight if necessary.
up to 60 hours after study drug administration
Amount of Drug Excreted in Urine (Ae)
Time Frame: up to 60 hours after study drug administration
Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.
up to 60 hours after study drug administration
Percentage of Drug dose Excreted into Urine
Time Frame: up to 60 hours after study drug administration
Total amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae/dose)*100, and corrected for molecular weight if necessary.
up to 60 hours after study drug administration
Renal Clearance
Time Frame: up to 60 hours after study drug administration
Renal clearance calculated as Ae/AUC (infinity).
up to 60 hours after study drug administration
Ae Metabolite to Parent Ratio (MPR Ae)
Time Frame: up to 60 hours after study drug administration
Ae metabolite to parent ratio, and corrected for molecular weight if necessary.
up to 60 hours after study drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to Day 11
An AE 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. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Baseline up to Day 11

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 27, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 27, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 19, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR108098
  • ESKETINTRD1011 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

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