A Study to Evaluate the Pharmacokinetics of the Hydrocodone Extended-Release Tablet (CEP-33237) in Subjects With Normal Hepatic Function and Subjects With Moderate Hepatic Impairment

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is: To assess the pharmacokinetics of the hydrocodone bitartrate extended-release tablet in subjects with moderate hepatic impairment and in subjects with normal hepatic function. To assess the safety and tolerability of the hydrocodone bitartrate extended-release tablet in subjects with moderate hepatic impairment and in subjects with normal hepatic function.

Official Title
-----------------
An Open-Label, Single-Dose, Parallel-Group Study to Assess the Pharmacokinetics of the Hydrocodone Bitartrate Extended-Release Tablet (15 mg) in Subjects With Normal Hepatic Function and Subjects With Moderate Hepatic Impairment

Conditions
-----------------
Hepatic Impairment

Intervention / Treatment
-----------------
* Drug: Hydrocodone bitartrate extended-release tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All subjects: Written informed consent is obtained Subjects with normal hepatic function: The subject is in generally good health (age-appropriate) as determined by medical and psychiatric history, physical examination, ECG, serum chemistry, hematology, coagulation, urinalysis, and serology. Subjects with hepatic impairment: The subject's health is otherwise clinically stable as determined by medical history, physical examination, ECG, serum chemistry, hematology, coagulation parameters (PT, activated partial thromboplastin time [aPTT], and international normalized ratio [INR]), urinalysis, and serology except for those signs and symptoms attributable to liver disease. The subject has case record notes demonstrating physical signs consistent with 1 or more of the following characteristic clinical manifestations of liver cirrhosis: liver firmness to palpation, splenic enlargement, spider angiomas, palmar erythema, parotid hypertrophy, testicular atrophy, ascites (accumulation of fluid in the abdominal cavity), or gynecomastia. The subject has a Child-Pugh Classification score of 7-9 points (moderate). Exclusion Criteria: All subjects: The subject has any clinically significant, uncontrolled medical condition. The subject is a poor metabolizer of CYP2D6 substrates based on genotyping performed at screening. The subject has previously participated in a study with CEP-33237. The subject has a known sensitivity or idiosyncratic reaction to hydrocodone or hydromorphone, related compounds, or to any metabolites, or any compound listed as being present in a study formulation. Subjects with normal hepatic function: The subject has a positive test result for HBsAg or antibodies to hepatitis C. The subject has a history of alcohol, narcotic, or any other substance abuse. Subjects with hepatic impairment: The subject has severe ascites. The subject has an acute exacerbation of liver disease as indicated by worsening clinical signs of hepatic impairment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: Normal Hepatic Function<br>Intervention Drug: Hydrocodone bitartrate extended-release tablet | Drug: Hydrocodone bitartrate extended-release tablet<br>* 15 mg (single dose)<br>|
| Experimental: Moderate Hepatic Impairment<br>Intervention Drug: Hydrocodone bitartrate extended-release tablet | Drug: Hydrocodone bitartrate extended-release tablet<br>* 15 mg (single dose)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (AUC and Cmax) after a single dose |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (occurrence of adverse events, labs, ECG, physical exam, vital signs, oxygen saturation) |  | throughout the 37 day study period (includes screening, drug administration and pharmacokinetics sampling period, and follow-up) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, Hydrocodone, Extended Release, Hepatic impairment