A Study to Assess the Effect of Hepatic Impairment on Safinamide Pharmacokinetics

Study Overview
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Brief Summary
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The primary purpose of this study is to investigate the pharmacokinetics (behavior of the compound in the body) of safinamide in patients with different degrees of hepatic (liver) impairment in comparison to matched subjects with normal hepatic function.

Official Title
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An Open-label, Parallel-group, Single Centre, Single Oral Dose Study to Investigate the Pharmacokinetics of 50 mg Safinamide in Subjects With Mild and Moderate Hepatic Impairment as Compared to Matched Subjects With Normal Hepatic Function

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: safinamide
* Drug: safinamide
* Drug: safinamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatically impaired subjects - Subjects with liver cirrhosis and different degrees of impaired hepatic function: mild and moderate impaired hepatic function (Grade A, or B according to Child-Pugh classification) Healthy subjects - Subject is in good age-appropriate physical and mental health as established by medical history, physical examination, ECG and vital signs recordings, and results of biochemistry, haematology, coagulation and urinalysis testing within 3 weeks prior to the dosing All subject have given written informed consent before any study-related activities are carried out Exclusion Criteria: Any clinically relevant disease or condition, which in the Investigator's opinion would exclude the subject from the study Diseases or surgeries of the gastrointestinal tract, which could influence the gastro-intestinal absorption and/or motility Hepatically impaired subjects - Subjects with primary biliary liver cirrhosis, hepatic encephalopathy grade III and IV, sepsis or spontaneous bacterial peritonitis, gastrointestinal bleeding within one month before the study, esophagus varices > grade II, acute hepatic failure of any aetiology, portosystemic shunt, renal impairment (creatinine clearance < 50 mL/min calculated by use of Cockroft Gault formula) Healthy subjects - Use of any medication, including multi-vitamin preparations, received within 21 days prior to the drug administration, or within six times the elimination half-life, whichever is longest, except combined oral contraceptives and occasional use of paracetamol or ibuprofen within 14 days before study drug administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>subjects with mild hepatic impairment | Drug: safinamide<br>* single dose of 50mg safinamide on Day 1<br>|
| Experimental: Arm 2<br>subjects with moderate hepatic impairment | Drug: safinamide<br>* single dose of 50mg safinamide on Day 1<br>|
| Experimental: Arm 3<br>matched subjects with normal hepatic function | Drug: safinamide<br>* single dose of 50mg safinamide on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of safinamide after single dose administration (Cmax) |  | 10 days | 
| Pharmacokinetics of safinamide after single dose administration (AUC) |  | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability after single dose administration of safinamide (Adverse Events) |  | 12 days | 
| Pharmacokinetics of safinamide metabolite NW1153 (Cmax) |  | 10 days | 
| Pharmacokinetics of safinamide metabolite NW1153 (AUC) |  | 10 days | 
| Pharmacokinetics of safinamide metabolite NW1689 (Cmax) |  | 10 days | 
| Pharmacokinetics of safinamide metabolite NW1689 (AUC) |  | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment, Liver diseases, Pharmacokinetics, To Investigate Pharmacokinetics of Safinamide in Subjects With Mild and Moderate Hepatic Impairment as Compared to Healthy Subjects With Normal Hepatic Function