Hepatic ImpairmentPhase 1NCT02611505

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

A Phase 1 study testing Esketamine in people with Hepatic Impairment and Normal Hepatic Function, run by Janssen Research & Development, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Hepatic Impairment, Normal Hepatic Function
What is being tested?: Esketamine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: 30 Nov 2015to 27 Feb 2017
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 10Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Knoxville, Tennessee

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Hepatic Impairment, Normal Hepatic Function
Being tested: Esketamine
Keywords: Healthy, Esketamine, Hepatic Impairment, Pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EsketamineDrug
Also called JNJ-54135419
Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.

Study groups in NCT02611505
Study group	Role	What they receive
Cohort 1	Experimental	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. Receives: Drug: Esketamine
Cohort 2	Experimental	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. Receives: Drug: Esketamine
Cohort 3	Experimental	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. Receives: Drug: Esketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Plasma Concentration (Cmax)
The Cmax is the maximum plasma concentration.
Measured: up to 60 hours after study drug administration
Time to Reach Maximum Concentration (tmax)
Time to reach the maximum observed plasma concentration.
Measured: up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last (AUC [0-last])
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.
Measured: up to 60 hours after study drug administration
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; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
Measured: up to 60 hours after study drug administration
Elimination Half-life period (t1/2) Associated with the Terminal Slope (Lambda z)
Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Measured: up to 60 hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours (AUC [0-12])
The AUC (0-12) is the area under the plasma concentration-time curve from time 0 to 12 hours post-dose.
Measured: up to 12 hours after study drug administration
Rate Constant (Lambda[z])
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.
Measured: up to 60 hours after study drug administration
Cmax Metabolite to Parent Ratio (MPR Cmax)
Cmax metabolite to parent ratio, and corrected for molecular weight if necessary.
Measured: up to 60 hours after study drug administration
AUC(last) Metabolite to Parent Ratio (MPR AUC[last])
AUC(last) metabolite to parent ratio, and corrected for molecular weight if necessary.
Measured: up to 60 hours after study drug administration
AUC (infinity) Metabolite to Parent Ratio (MPR AUC [infinity])
AUC (infinity) metabolite to parent ratio, and corrected for molecular weight if necessary.
Measured: up to 60 hours after study drug administration
Amount of Drug Excreted in Urine (Ae)
Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.
Measured: up to 60 hours after study drug administration
Percentage of Drug dose Excreted into Urine
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.
Measured: up to 60 hours after study drug administration
Renal Clearance
Renal clearance calculated as Ae/AUC (infinity).
Measured: up to 60 hours after study drug administration
Ae Metabolite to Parent Ratio (MPR Ae)
Ae metabolite to parent ratio, and corrected for molecular weight if necessary.
Measured: up to 60 hours after study drug administration

Secondary outcomes (1)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Measured: Baseline up to Day 11

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Nov 201527 Feb 2017

First posted20 Nov 2015 (estimated)
Study start30 Nov 2015
Primary completion27 Feb 2017
Study completion27 Feb 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02611505
Sponsor's protocol ID: CR108098
Other IDs: ESKETINTRD1011
Status last verified: Jan 2025
First submitted: 19 Nov 2015
Last updated: 3 Feb 2025
Results posted: No
Data monitoring committee: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02611505
Acronym / sponsor ID: CR108098
Conditions: Hepatic Impairment, Normal Hepatic Function
Keywords: Healthy, Esketamine, Hepatic Impairment, Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
Study start: 30 Nov 2015 (actual)
Primary completion: 27 Feb 2017 (actual)
Study completion: 27 Feb 2017 (actual)
First posted: 20 Nov 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Experimental	Drug: EsketamineParticipants 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.
Cohort 2	Experimental	Drug: EsketamineParticipants 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.
Cohort 3	Experimental	Drug: EsketamineParticipants 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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
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

Key exclusion criteria (10 listed)

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
History of hepatopulmonary syndrome, hydrothorax or hepatorenal syndrome
Positive test for alcohol or drugs of abuse per local standard practices
Clinically significant medical illness

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EsketamineAlso: JNJ-54135419Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.	Drug	Cohort 1, Cohort 2, Cohort 3

Primary outcome

Maximum Plasma Concentration (Cmax)
Time frame: up to 60 hours after study drug administration
The Cmax is the maximum plasma concentration.
Time to Reach Maximum Concentration (tmax)
Time frame: up to 60 hours after study drug administration
Time to reach the maximum observed plasma concentration.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
Renal Clearance
Time frame: up to 60 hours after study drug administration
Renal clearance calculated as Ae/AUC (infinity).
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.

1 secondary outcome

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Day 11

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Janssen Research & Development, LLC Clinical Trial study director

Janssen Research & Development, LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Esketamine in people with Hepatic Impairment and Normal Hepatic Function, run by Janssen Research & Development, LLC at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Plasma Concentration (Cmax) (time frame: up to 60 hours after study drug administration). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02611505.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.