Pharmacokinetics of AGO178 in Participants With Liver Impairment

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AGO178

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Servier

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2011
• Primary Completion (Actual): September 2, 2011
• Study Completion (Actual): September 2, 2011

Study Registration Dates

• First Submitted: February 3, 2012
• First Submitted That Met QC Criteria: February 8, 2012
• First Posted (Estimate): February 10, 2012

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Liver impairment; Major Depression Disorder; Sublingual tablet
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; S 20098
• Other Study ID Numbers: CAGO178C2102