Pharmacokinetics, Safety, and Tolerability of Methylnaltrexone in Volunteers With Impaired Hepatic Function

Study Overview
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Brief Summary
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This is a multicenter, non-randomized, single-dose, parallel-group study. Each subject will receive a subcutaneous dose of MNTX. Eight subjects with normal hepatic function and eight subjects from each classification of hepatic impairment will be enrolled. Plasma samples will be collected before and at specified intervals after dosing and the concentration of MNTX will be analyzed.

Official Title
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A Phase 1, Open-Label, Study to Evaluate Single Dose Pharmacokinetics, Safety, and Tolerability of Methylnaltrexone (MNTX) in Volunteers With Impaired Hepatic Function

Conditions
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Liver Dysfunction

Intervention / Treatment
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* Drug: SC Methylnaltrexone (MNTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 18-80 years Body weight greater than 100 lbs and BMI between 18-38 Liver values that are abnormal must not be clinically relevant as judged by the investigator. Liver enzyme and bilirubin must be less than 5 times the upper normal of reference range and may be repeated under fed conditions if abnormal. Stable hepatitis patients as well as cirrhosis patients of either etiology. Exclusion Criteria: History of current alcohol abuse with less than 1 year abstinence Conditions possibly affecting drug absorption, e.g. gastrectomy or clinically significant diabetic gastroenteropathy. Currently pregnant or nursing Methadone use.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: SC Methylnaltrexone (MNTX)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of SC MNTX | To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls. | 20 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Plasma Concentration of SC MNTX | To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls. | 20 days | 
| Area Under the Plasma Concentration versus Time Curve (AUC) of SC MNTX | To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls. | 20 days | 
| Percentage of SC MNTX Excreted in Urine | To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls. | 20 days | 
| Urinary Clearance of SC MNTX | To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls. | 20 days |