Clinical trial NCT02611505: A Study to Assess the Effects of Hepatic 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 Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Normal Hepatic Function
Keywords: Healthy
Esketamine
Hepatic Impairment
Pharmacokinetics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: up to 60 hours after study drug administration
measure: Time to Reach Maximum Concentration (tmax)
timeFrame: up to 60 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last (AUC [0-last])
timeFrame: up to 60 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: up to 60 hours after study drug administration
measure: Elimination Half-life period (t1/2) Associated with the Terminal Slope (Lambda z)
timeFrame: up to 60 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours (AUC [0-12])
timeFrame: up to 12 hours after study drug administration
measure: Rate Constant (Lambda[z])
timeFrame: up to 60 hours after study drug administration
measure: Cmax Metabolite to Parent Ratio (MPR Cmax)
timeFrame: up to 60 hours after study drug administration
measure: AUC(last) Metabolite to Parent Ratio (MPR AUC[last])
timeFrame: up to 60 hours after study drug administration
measure: AUC (infinity) Metabolite to Parent Ratio (MPR AUC [infinity])
timeFrame: up to 60 hours after study drug administration
measure: Amount of Drug Excreted in Urine (Ae)
timeFrame: up to 60 hours after study drug administration
measure: Percentage of Drug dose Excreted into Urine
timeFrame: up to 60 hours after study drug administration
measure: Renal Clearance
timeFrame: up to 60 hours after study drug administration
measure: Ae Metabolite to Parent Ratio (MPR Ae)
timeFrame: up to 60 hours after study drug administration
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 11
Other outcomes:
Locations:
city: Knoxville
country: United States
state: Tennessee
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: