Clinical trial NCT01319279: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Pharmacokinetics
Hydrocodone
Extended Release
Hepatic impairment
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics (AUC and Cmax) after a single dose
timeFrame: 7 days
Secondary outcomes:
measure: Safety (occurrence of adverse events, labs, ECG, physical exam, vital signs, oxygen saturation)
timeFrame: throughout the 37 day study period (includes screening, drug administration and pharmacokinetics sampling period, and follow-up)
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research
state: Florida
Study officials:
affiliation: Cephalon, Inc.
name: Sponsor's Medical Expert
role: STUDY_DIRECTOR
References: