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

Cephalon

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Hydrocodone bitartrate extended-release tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT01319279

C33237/1089

Details and patient eligibility

About

The purpose of this study is:

1. To assess the pharmacokinetics of the hydrocodone bitartrate extended-release tablet in subjects with moderate hepatic impairment and in subjects with normal hepatic function.
2. 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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. All subjects:

   • Written informed consent is obtained

2. 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.

3. 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

1. 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.

2. 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.

3. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Normal Hepatic Function

Experimental group

Description:

Intervention Drug: Hydrocodone bitartrate extended-release tablet

Treatment:

Drug: Hydrocodone bitartrate extended-release tablet

Moderate Hepatic Impairment

Experimental group

Description:

Intervention Drug: Hydrocodone bitartrate extended-release tablet

Treatment:

Drug: Hydrocodone bitartrate extended-release tablet