Pharmacokinetics and Metabolism of Hydrocodone Bitartrate Controlled-Release (HC-CR) in Subjects With Hepatic Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02242734
Recruitment Status : Completed
First Posted : September 17, 2014
Last Update Posted : September 17, 2014
Information provided by (Responsible Party):
Zogenix, Inc.

Brief Summary:
Determine the influence of hepatic impairment on the pharmacokinetics and metabolism of Hydrocodone Bitartrate Extended-Release (HC-ER) 20 mg capsules

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: 20 mg HC-ER Phase 1

Detailed Description:
Pharmacokinetics and relative bioavailability of hydrocodone and its metabolites under fasted conditions

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Evaluation of the Effect of Hepatic Impairment on the Pharmacokinetics and Metabolism of Hydrocodone and Its Metabolites Following Administration of Hydrocodone Bitartrate Extended-Release (HC-ER) 20mg Capsules
Study Start Date : February 2011
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Mild Hepatic Impairment
20 mg HC-ER
Drug: 20 mg HC-ER
1-72 hours
Other Name: Zohydro ER

Experimental: Moderate Hepatic Impairment
20 mg HC-ER
Drug: 20 mg HC-ER
1-72 hours
Other Name: Zohydro ER

Experimental: No Hepatic Impairment
20 mg HC-ER
Drug: 20 mg HC-ER
1-72 hours
Other Name: Zohydro ER

Primary Outcome Measures :
  1. Pharmacokinetic profile of hydrocodone and its metabolites of 20 mg HC-ER [ Time Frame: Day 1-3 ]
    PK parameters including Cmax, Tmax, , AUC 0-t, AUC 0-inf, T1/2 and Kel

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. All hepatically-impaired subjects must have meet all of the following inclusion criteria to be enrolled into the study:
  2. Male or non-pregnant, non-lactating females. Subjects were aged 18-80 years, inclusive.
  3. Subjects must have been a clinical diagnosis of chronic hepatic impairment for duration of at least 6 months classified as mild or moderate as per Child-Pugh classification.
  4. Hepatic insufficiency was stable with no acute episodes of illness within the previous 2 months due to deterioration of hepatic function due to any etiology.
  5. Female subjects of childbearing potential including those who had a tubal ligation surgery but excluded those who did not have a menstrual period for a minimum of 2 years, had a negative pregnancy test at the Screening and Day -1 visits, and consented to use a medically-acceptable method of contraception throughout the entire study period and for 1 week after the study completed. Medically acceptable methods of contraception included were not limited to abstinence, birth control pills or patches, vaginal rings, diaphragm with vaginal spermicide, Intrauterine Device, and progestin implant or injection (used consistently for 3 months prior to study dosing).
  6. Subjects voluntarily provided written informed consent.
  7. Subjects, in the Investigator's opinion, were able to complete study procedures

    • All healthy control subjects must have met all hepatic subject inclusion criteria as outlined above with the exception of Inclusion Criteria 3 & 4 above which should be substituted with the following to be enrolled into the study:
    • Must have been matched by age (±10 years) and Body Mass Index (BMI) (± 10% of BMI) with some consideration for race and gender to subjects with hepatic impairment.
    • Were medically healthy with no clinically significant abnormalities in their laboratory profile as deemed by the Investigator.

Exclusion Criteria:

  1. Women who were pregnant or breastfeeding
  2. Any clinically significant condition that would, in the opinion of the Investigator, preclude study participation
  3. Uncontrolled blood pressure, i.e., subject has a sitting systolic blood pressure 180 mmHg or 90 mmHg, and/or a sitting diastolic blood pressure 120 mmHg or 50 mmHg at Screening.
  4. Body Mass Index (BMI) >40 kg/m2.
  5. Known allergy or hypersensitivity to hydrocodone, or other opioids.
  6. Had taken any investigational drug within 30 days prior to the Day 1 Visit or currently enrolled in another investigational drug study.
  7. Had used a monoamine oxidase inhibitor within 14 days prior to Day 1.
  8. Been taking opioids during the 30 days prior to Day 1 or needing to take opioids during the study period
  9. Positive for human immunodeficiency virus (HIV). Healthy control subjects must not have been hepatitis C virus (HCV) positive, hepatically-impaired subjects could be HCV positive but should not have been receiving treatment.
  10. History of any illicit substance abuse in the past 2 years or any history of opioid abuse. Subjects should not have been current abusers of alcohol and must have had a negative serum alcohol level at Screening and Day -1.
  11. Positive quantitative urine drug screen for illicit drugs, or non-prescribed controlled substances at Screening.
  12. Had made a plasma donation within 7 days prior to Day 1.
  13. Had made any significant donation or loss of blood within 56 days prior to Day 1.
  14. Had taken CYP2D6 and/or CYP3A4 inhibitors within 7 days prior to Day 1 and/or CYP2D6 and/or CYP3A4 inducers within 21 days prior to Day 1.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02242734

Sponsors and Collaborators
Zogenix, Inc.
Study Director: Kenneth Lasseter, MD Zogenix, Inc.

Responsible Party: Zogenix, Inc. Identifier: NCT02242734     History of Changes
Other Study ID Numbers: ZX002-1001
First Posted: September 17, 2014    Key Record Dates
Last Update Posted: September 17, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents