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

NCT02611505 | Completed Phase 1

• 2 other identifiers: CR108098ESKETINTRD1011
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatic Impairment; Normal Hepatic Function

Keywords

Healthy; Esketamine; Hepatic Impairment; Pharmacokinetics

Outcome Measures

Primary Outcomes (14)

• Maximum Plasma Concentration (Cmax)

  The Cmax is the maximum plasma concentration.

  up to 60 hours after study drug administration

• Time to Reach Maximum Concentration (tmax)

  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])

  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])

  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)

  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])

  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])

  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)

  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])

  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])

  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)

  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

  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

  Renal clearance calculated as Ae/AUC (infinity).

  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.

  up to 60 hours after study drug administration

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to Day 11

Study Arms (3)

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.

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.

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.

Drug: Esketamine

Interventions

Esketamine DRUG

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

Also known as: JNJ-54135419

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Knoxville, Tennessee, United States

Location

MeSH Terms

Interventions

Esketamine

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 20, 2015
• Study Start: November 30, 2015
• Primary Completion: February 27, 2017
• Study Completion: February 27, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (1)