Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects
Condition: Hepatic Failure; Hepatic Impairment; Chronic Hepatitis C Infection With Hepatic Coma
MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Failure; Hepatic Insufficiency; Hepatic Encephalopathy
Intervention: 2.0mg Buprenorphine/0.5mg Naloxone; Promethazine
Intervention description: Each participant received a single sublingual dose of Suboxone® on Day 1 following a fast of at least 8 hours prior to dosing and 2 hours after dosing.; Each participant received a 25-mg or 50-mg promethazine oral dose 30 minutes before Suboxone® administration and then 25-mg promethazine orally or by rectal suppositories every 4 hours as needed for nausea and vomiting during the first 48 hours after Suboxone® administration.
Intervention MeSH terms: Promethazine; Diphenhydramine; Buprenorphine; Naloxone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hepatic; Hepatitis C Virus; Suboxone; Buprenorphine; Naloxone

Summary:

      The objective was to determine if hepatitis C virus (HCV) infection or mild to severe hepatic
      impairment (Child-Pugh Classes A, B, and C) altered the PK of buprenorphine,
      norbuprenorphine, or naloxone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females between the ages of 18 and 65 years, inclusive

          -  Females should be surgically sterile, 2 years post-menopausal or have a negative
             plasma β-human chorionic gonadotropin (β-hCG) pregnancy test. Subjects of
             child-bearing potential must take reasonable precautions during the study to avoid
             pregnancy by agreeing to remain abstinent or to practice double-barrier forms of birth
             control from the time of informed consent through the last study visit. A negative
             plasma pregnancy (β-hCG) test at Screening and upon admission to the investigational
             site. Testing for β-hCG will need to be timed to ensure a negative pregnancy result at
             Day 1.

          -  Male subject agrees to use barrier contraception and spermicide when engaging in
             sexual activity with a female of child-bearing potential for at least 28 days after
             the study medication dose.

          -  Male subject agrees to refrain from sperm donations for the entire duration of the
             study and for at least 90 days after the study drug dose.

          -  Body mass index (BMI) of ≥ 18 to ≤ 33 kg^m2.

          -  Subject agrees to the conditions of the study and signs the informed consent form

        Exclusion Criteria:

          -  Medical conditions: (a) pregnancy; and (b) breastfeeding

          -  Psychiatric conditions: (a) current treatment for opioid addiction with substitution
             therapies; (b) active history of bipolar I, bipolar II, schizophrenia,
             schizophreniform; schizoaffective; mania, hypomania, or severe post-traumatic stress
             disorder; and (c) presence of suicidal behavior within the year before informed
             consent or suicidal intent within the 30 days before informed consent as documented by
             the Columbia Suicide Severity Rating Scale

          -  Hypersensitivity to opioids, defined as intractable vomiting, severe constipation, or
             severe pruritus after opioid treatment

          -  Subject has a known intolerance or hypersensitivity to buprenorphine or naloxone or
             any excipients in the Suboxone tablet formulation

          -  In the judgment of the investigator, any other condition that would preclude safe,
             useful, or consistent participation in the study

          -  Use of any investigational medication or investigational medical device in the 30 days
             before informed consent

          -  Hepatic encephalopathy greater than West Haven Grade 2

          -  Donation of > 250 ml of blood within previous 30 days

          -  Systolic BP ≤ 90 or ≥ 160 mmHg and/or Diastolic BP < 60 mmHg or > 100 mmHg

          -  History of cholecystectomy

          -  History or current acquired immunodeficiency syndrome (AIDS) or human immunodeficiency
             virus (HIV) antibodies

          -  Estimated creatinine clearance rate (eC Cr) using Cockcroft-Gault formula < 60 mL/min

          -  More than 1 missed appointment during Screening

          -  Currently under mandate by the criminal justice system or Child and Family Services to
             participate in drug abuse treatment

          -  Participation in drug or alcohol dependence treatment in the 30 days before informed
             consent

          -  Positive urine drug screen result for amphetamines, methamphetamine, barbiturates,
             benzodiazepines, buprenorphine, cannabinoids, cocaine, methadone, opioids, oxycodone,
             or phencyclidine which, in the judgment of the investigator, is indicative of
             non-prescribed drug use; and/or positive urine alcohol screen result in which, in the
             judgment of the investigator, is indicative of alcohol abuse or alcoholism

          -  Consumption of prohibited medications within 1 week of informed consent, including
             buprenorphine

          -  Consumption of grapefruit and grapefruit juice for at least one week before the study
             dose and until the end of the study