Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01846455
• Other study ID #: RB-US-08-0003
• Status: Completed
• Phase: Phase 4
• First received: May 1, 2013
• Last updated: August 20, 2013
• Start date: August 2012
• Est. completion date: August 2013

Study information

• Verified date: May 2013
• Source: Indivior Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Pharmacokinetics of Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment and in HCV-Seropositive Subjects, and in Healthy Volunteers.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 ß-human chorionic gonadotropin (ß-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 (ß-hCG) test at Screening and upon admission to the investigational site. Testing for ß-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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection With Hepatic Coma
• Hepatic Failure
• Hepatic Impairment
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Liver Diseases
• Liver Failure

Intervention

Drug:
• 2.0mg Buprenorphine/0.5mg Naloxone
Each participant will receive 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
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.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami, Inc.	Hialeah	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	American Research Corporation (ARC)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Indivior Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Maximum Observed Plasma Concentration (CMAX) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Time to reach the maximum plasma concentration (tmax) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Terminal elimination rate-constant (?z) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Terminal elimination half-life (t1/2) of buprenorphine, norbuprenorphine and naloxone		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Apparent body clearance (CL/F) of buprenorphine		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No
Primary	Apparent volume of distribution (Vdz/F) of buprenorphine		before dosing (time 0; Baseline) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after dosing	No