Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects

NCT ID: NCT01846455

Last Updated: 2016-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2013-05-31

Brief 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.

Detailed Description

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

Conditions

Hepatic Failure; Hepatic Impairment; Chronic Hepatitis C Infection With Hepatic Coma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hepatic Impairment: Child-Pugh A

Participants with chronic liver disease and classified as Child-Pugh Grade A had a score of 5-6 (out of 15) which correlates with a good prognosis. Each participant received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.

Group Type: EXPERIMENTAL

2.0mg Buprenorphine/0.5mg Naloxone

Intervention Type: DRUG

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.

Promethazine

Intervention Type: DRUG

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.

Hepatic Impairment: Child-Pugh B

Participants with chronic liver disease and classified as Child-Pugh Grade B had a score of 7-9 (out of 15) which correlates with significant functional liver compromise. Each participant received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.

Group Type: EXPERIMENTAL

2.0mg Buprenorphine/0.5mg Naloxone

Intervention Type: DRUG

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.

Promethazine

Intervention Type: DRUG

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.

Hepatic Impairment: Child-Pugh C

Participants with chronic liver disease and classified as Child-Pugh Grade C had a score of 10-15 (out of 15) which correlates with decompensated liver disease. Each participant received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.

Group Type: EXPERIMENTAL

2.0mg Buprenorphine/0.5mg Naloxone

Intervention Type: DRUG

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.

Promethazine

Intervention Type: DRUG

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.

HCV Without Hepatic Impairment

Participants with hepatitis C virus (HCV) without hepatic impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.

Group Type: EXPERIMENTAL

2.0mg Buprenorphine/0.5mg Naloxone

Intervention Type: DRUG

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.

Promethazine

Intervention Type: DRUG

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.

No Hepatic Disease or Impairment

Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.

Group Type: ACTIVE_COMPARATOR

2.0mg Buprenorphine/0.5mg Naloxone

Intervention Type: DRUG

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.

Promethazine

Intervention Type: DRUG

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.

Interventions

2.0mg Buprenorphine/0.5mg Naloxone

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.

Intervention Type: DRUG

Promethazine

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 Type: DRUG

Other Intervention Names

Suboxone®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Indivior Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Lasseter, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Pharmacology of Miami, Inc.

Thomas Marabury, MD

Role: PRINCIPAL_INVESTIGATOR

Orlando Clinical Research Center

Eric J. Lawitz, MD

Role: PRINCIPAL_INVESTIGATOR

American Research Corporation (ARC)

Locations

Clinical Pharmacology of Miami, Inc.

Hialeah, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

American Research Corporation (ARC)

San Antonio, Texas, United States

Countries

United States

References

Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers. Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6.

Reference Type: RESULT

PMID: 25603822 (View on PubMed)

Other Identifiers

RB-US-08-0003

Identifier Type: -

Identifier Source: org_study_id