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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Normal Hepatic Function

Treatments: Drug: Esketamine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02611505

ESKETINTRD1011 (Other Identifier)

CR108098

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Esketamine

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Esketamine

Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: Esketamine