Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects

Pharmacokinetics of Buprenorphine and Naloxone in Subjects With Mild to Severe Hepatic Impairment (Child-Pugh Classes, A, B, and C), in HCV-Seropositive Subjects, and in Healthy Volunteers

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.

This will be a multi-center, open-label study. After providing informed consent, subjects will undergo an outpatient screening period of up to 21 days. Screening procedures will include an assessment of mental status which will be repeated before dosing. Eligible subjects will then undergo hospital intake procedures and reside at the investigational site until Day 5. Subjects will be enrolled in 5-treatment groups as follows: (1) Group 1: Subjects with hepatic impairment classified as Child-Pugh A; (2) Group 2: Subjects with hepatic impairment classified as Child-Pugh B; (3) Group 3: Subjects with hepatic impairment classified as Child-Pugh C; (4) Group 4: Subjects with Hepatitis C Virus (HCV) infection but without hepatic impairment; and (5) Group 5: Subjects without hepatic disease or impairment. Group 5 is used as a control group

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