Hepatic Impairment, Normal Hepatic Function
Conditions
Keywords
Healthy, Esketamine, Hepatic Impairment, Pharmacokinetics
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.
Interventions
DRUGEsketamine
Esketamine 28 mg will be self-administered by participants as intranasal spray at 0 hour (h) on Day 1.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ae Metabolite to Parent Ratio (MPR Ae) | up to 60 hours after study drug administration | Ae metabolite to parent ratio, and corrected for molecular weight if necessary. |
| Maximum Plasma Concentration (Cmax) | up to 60 hours after study drug administration | The Cmax is the maximum plasma concentration. |
| Time to Reach Maximum Concentration (tmax) | 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]) | 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]) | 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) | 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]) | 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]) | 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) | 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]) | 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]) | 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) | 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 | 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 | up to 60 hours after study drug administration | Renal clearance calculated as Ae/AUC (infinity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Day 11 | 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. |
Countries
United States
Outcome results
None listed