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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611505
• Other study ID #: CR108098
• Secondary ID: ESKETINTRD1011
• Status: Completed
• Phase: Phase 1
• First received: November 19, 2015
• Last updated: May 12, 2017
• Start date: November 30, 2015
• Est. completion date: February 27, 2017

Study information

• Verified date: May 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 27, 2017
• Est. primary completion date: February 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases
• Normal Hepatic Function

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax)	The Cmax is the maximum plasma concentration.	up to 60 hours after study drug administration
Primary	Time to Reach Maximum Concentration (tmax)	Time to reach the maximum observed plasma concentration.	up to 60 hours after study drug administration
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Renal Clearance	Renal clearance calculated as Ae/AUC (infinity).	up to 60 hours after study drug administration
Primary	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	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.	Baseline up to Day 11