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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Hydrocodone bitartrate extended-release tablet

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Hepatic Function; Intervention Drug: Hydrocodone bitartrate extended-release tablet	Drug: Hydrocodone bitartrate extended-release tablet; 15 mg (single dose)
Experimental: Moderate Hepatic Impairment; Intervention Drug: Hydrocodone bitartrate extended-release tablet	Drug: Hydrocodone bitartrate extended-release tablet; 15 mg (single dose)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Cephalon

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 18, 2011
• First Posted (Estimate): March 21, 2011

Study Record Updates

• Last Update Posted (Estimate): April 24, 2012
• Last Update Submitted That Met QC Criteria: April 20, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hydrocodone; Extended Release; Hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Hydrocodone
• Other Study ID Numbers: C33237/1089

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No