Pharmacokinetics of AGO178 in Participants With Liver Impairment

Study Overview
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Brief Summary
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AGO178 was developed for the treatment of depression. A new formulation is being tested in the present study: a tablet to be placed and dissolved under the tongue (sublingual tablet). The goal of this trial was to study the pharmacokinetics of agomelatine given as sublingual tablet in participants with liver impairment and to compare the results to those of healthy volunteers who receive the same treatment.

Official Title
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An Open-Label, Parallel-Group Study to Compare the Pharmacokinetics, Safety and Tolerability of a Single Sublingual 1 mg Dose of AGO178 in Subjects With Mild and Moderate Hepatic Impairment With That in Matched Healthy Control Subjects

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: AGO178


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with liver disease confirmed within 3 months of screening. If liver impairment is caused by alcohol use, participants must have abstained from alcohol use within 3 months of study start. Participants must satisfy criteria for Child- Pugh Class A or B. Exclusion Criteria: Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless using effective contraception during the study. Donation or loss of 400 millilitres (mL) or more of blood within eight (8) weeks prior to initial dosing. Significant illness within the two weeks prior to the dosing. Participants with Child-Pugh alterations due to a non-liver disease (e.g. cancer or treatment related weight loss). Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild Hepatic Impaired Participants<br>Mild hepatic impaired participants will receive a single sublingual dose of AGO178, 1 milligram (mg) on Day 1. | Drug: AGO178<br>* AGO178 is administered as a sublingual tablet.<br>* Other names: Agomelatine;|
| Experimental: Moderate Hepatic Impaired Participants<br>Moderate hepatic impaired participants will receive a single sublingual dose of AGO178, 1 mg on Day 1. | Drug: AGO178<br>* AGO178 is administered as a sublingual tablet.<br>* Other names: Agomelatine;|
| Experimental: Healthy Participants Matched by Aged, Gender and Body Mass Index (BMI)<br>Healthy participants matched by aged, gender and BMI will receive a single sublingual dose of AGO178, 1 mg on Day 1. | Drug: AGO178<br>* AGO178 is administered as a sublingual tablet.<br>* Other names: Agomelatine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of AGO178 | Blood samples will be collected at various time points on day 1 and day 2 | Predose, 2 minute (min) , 5 min , 10 min, 20 min, 30 min, 45 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 12h, 24h, 36h Post dose | 
| Area Under the Plasma Curve (AUC) of AGO178 | Blood samples will be collected at various time points on day 1 and day 2 | Predose, 2 min , 5 min , 10 min, 20 min, 30 min, 45 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 12h, 24h, 36h Post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | Adverse events will be based on evaluation of physical signs, electrocardiograms and clinical laboratory assessments (clinical chemistry, hematology, urinalysis). | Baseline and Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver impairment, Major Depression Disorder, Sublingual tablet