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Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects

Sponsor
Indivior Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01846455
Collaborator
(none)
43
Enrollment
3
Locations
5
Arms
8
Duration (Months)
14.3
Patients Per Site
1.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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

Study Design

Study Type:
Interventional
Actual Enrollment :
43 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Apr 1, 2013
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: 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.
Other Names:
  • Suboxone®

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • Suboxone®

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • Suboxone®

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • Suboxone®

    • 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.
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • Suboxone®

    • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

      AUC0-last was calculated for buprenorphine, norbuprenorphine, naloxone, and naloxone-3-β-D-glucuronide using non-compartmental analysis: AUC0-last = AUC from time 0 to the time of the last measurable plasma concentration, calculated using the linear trapezoidal rule.

    2. Maximum Observed Plasma Concentration (Cmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

    3. Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

      The extrapolation to infinity was done using the terminal phase. AUC0-inf = AUC0-last + Ct/λz Where Ct was the last observed quantifiable concentration and λz was the apparent terminal phase elimination rate constant.

    4. Time to Reach the Maximum Plasma Concentration (Tmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

    5. Time of the Last Measureable Plasma Concentration (Tlast) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

    6. Percentage of Area Under the Concentration-time Curve From Time Zero to Infinity Due to Extrapolation (%AUCextrap) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

      Calculated as: (AUC0-inf - AUC0-last)/AUC0-inf * 100 AUC0-inf, apparent body clearance (CL/F), and apparent volume of distribution during terminal phase (Vz/F) would not have been reported if %AUCextrap was > 20%.

    7. Terminal Phase Elimination Rate-Constant (λz) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

      For the determination of λz, only those data points judged to describe the terminal log-linear decline resulting in an adjusted coefficient of determination value (R2) > 0.7 were used in the regression. A minimum of 3 data points were used in calculating λz.

    8. Terminal Elimination Half-life (t1/2) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide [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]

      Terminal elimination half-life, calculated as ln(2)/λz. The terminal phase elimination half-life was calculated over a period of at least 2 half-lives.

    9. Apparent Body Clearance (CL/F) of Buprenorphine 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]

      Apparent body clearance (only for buprenorphine and naloxone), calculated as Dose/AUC0-inf.

    10. Apparent Volume of Distribution During Terminal Phase (Vz/F) of Buprenorphine 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]

      Apparent volume of distribution during terminal phase (only for buprenorphine and naloxone), calculated as Dose/(λz • AUC0-inf).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Pharmacology of Miami, Inc. Hialeah Florida United States 33014-3616
    2 Orlando Clinical Research Center Orlando Florida United States 32809
    3 American Research Corporation (ARC) San Antonio Texas United States 78215

    Sponsors and Collaborators

    • Indivior Inc.

    Investigators

    • Principal Investigator: Thomas Lasseter, MD, Clinical Pharmacology of Miami, Inc.
    • Principal Investigator: Thomas Marabury, MD, Orlando Clinical Research Center
    • Principal Investigator: Eric J. Lawitz, MD, American Research Corporation (ARC)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Indivior Inc.
    ClinicalTrials.gov Identifier:
    NCT01846455
    Other Study ID Numbers:
    • RB-US-08-0003
    First Posted:
    May 3, 2013
    Last Update Posted:
    Oct 24, 2016
    Last Verified:
    Sep 1, 2016
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Indivior Inc.
    Hepatic
    Hepatitis C Virus
    Suboxone
    Buprenorphine
    Naloxone
    Additional relevant MeSH terms:
    Hepatitis C
    Hepatitis C, Chronic
    Hepatitis
    Liver Failure
    Hepatic Insufficiency
    Hepatic Encephalopathy
    Promethazine
    Diphenhydramine
    Buprenorphine
    Naloxone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Period Title: Overall Study
    STARTED 9 8 8 10 8
    PK Population 6 7 6 6 8
    COMPLETED 9 8 8 10 8
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment Total
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1. Total of all reporting groups
    Overall Participants 9 8 8 10 8 43
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    58.0
    58.6
    53.9
    53.0
    57.1
    56.0
    Sex: Female, Male (Count of Participants)
    Female
    3
    33.3%
    4
    50%
    1
    12.5%
    6
    60%
    4
    50%
    18
    41.9%
    Male
    6
    66.7%
    4
    50%
    7
    87.5%
    4
    40%
    4
    50%
    25
    58.1%
    Race/Ethnicity, Customized (participants) [Number]
    White
    6
    66.7%
    7
    87.5%
    8
    100%
    8
    80%
    7
    87.5%
    36
    83.7%
    Black or African American
    2
    22.2%
    1
    12.5%
    0
    0%
    1
    10%
    1
    12.5%
    5
    11.6%
    Asian
    1
    11.1%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    2
    4.7%
    Weight (kg) [Mean (Full Range) ]
    Mean (Full Range) [kg]
    74.2
    75.4
    82.2
    74.7
    76.6
    76.5
    Body Mass Index (kg/m^2) [Mean (Full Range) ]
    Mean (Full Range) [kg/m^2]
    25.5
    27.0
    27.9
    26.2
    29.3
    27.1

    Outcome Measures

    1. Primary Outcome
    Title Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description AUC0-last was calculated for buprenorphine, norbuprenorphine, naloxone, and naloxone-3-β-D-glucuronide using non-compartmental analysis: AUC0-last = AUC from time 0 to the time of the last measurable plasma concentration, calculated using the linear trapezoidal rule.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine
    8.89
    (33.3)
    14.7
    (55.0)
    25.2
    (53.7)
    7.02
    (36.5)
    8.95
    (49.4)
    Norbuprenorphine
    12.5
    (119)
    9.51
    (71.4)
    2.25
    (118)
    9.91
    (43.4)
    15.0
    (51.8)
    Naloxone
    0.0726
    (41.8)
    0.291
    (195)
    1.28
    (60.2)
    0.0968
    (73.0)
    0.0915
    (50.9)
    Naloxone-3-β-D-Glucuronide
    19.3
    (31.9)
    27.9
    (33.6)
    20.6
    (40.2)
    19.1
    (21.8)
    22.5
    (15.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 99.34
    Confidence Interval (2-Sided) 90%
    66.05 to 149.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 163.88
    Confidence Interval (2-Sided) 90%
    110.82 to 242.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 281.43
    Confidence Interval (2-Sided) 90%
    187.10 to 423.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 78.43
    Confidence Interval (2-Sided) 90%
    52.14 to 117.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 126.66
    Confidence Interval (2-Sided) 90%
    81.87 to 195.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 208.94
    Confidence Interval (2-Sided) 90%
    137.21 to 318.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 358.83
    Confidence Interval (2-Sided) 90%
    231.92 to 555.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 78.09
    Confidence Interval (2-Sided) 90%
    44.03 to 138.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 74.78
    Confidence Interval (2-Sided) 90%
    39.26 to 142.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 11.45
    Confidence Interval (2-Sided) 90%
    6.35 to 20.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 71.08
    Confidence Interval (2-Sided) 90%
    39.00 to 129.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 109.90
    Confidence Interval (2-Sided) 90%
    58.14 to 207.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 105.23
    Confidence Interval (2-Sided) 90%
    52.17 to 212.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 16.12
    Confidence Interval (2-Sided) 90%
    8.40 to 30.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 79.30
    Confidence Interval (2-Sided) 90%
    40.03 to 157.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 317.58
    Confidence Interval (2-Sided) 90%
    164.93 to 611.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 1401.85
    Confidence Interval (2-Sided) 90%
    707.55 to 2777.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 105.78
    Confidence Interval (2-Sided) 90%
    53.39 to 209.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 74.97
    Confidence Interval (2-Sided) 90%
    36.09 to 155.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 300.22
    Confidence Interval (2-Sided) 90%
    148.44 to 607.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 1325.22
    Confidence Interval (2-Sided) 90%
    638.03 to 2752.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 85.87
    Confidence Interval (2-Sided) 90%
    66.06 to 111.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 123.77
    Confidence Interval (2-Sided) 90%
    96.27 to 159.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 91.26
    Confidence Interval (2-Sided) 90%
    70.21 to 118.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 84.78
    Confidence Interval (2-Sided) 90%
    65.23 to 110.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 101.28
    Confidence Interval (2-Sided) 90%
    76.52 to 134.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 145.99
    Confidence Interval (2-Sided) 90%
    111.43 to 191.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 107.64
    Confidence Interval (2-Sided) 90%
    81.33 to 142.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine
    1.10
    (52.2)
    1.04
    (46.5)
    1.40
    (27.4)
    0.933
    (30.5)
    0.913
    (53.2)
    Norbuprenorphine
    0.358
    (99.0)
    0.180
    (73.2)
    0.128
    (60.6)
    0.203
    (61.0)
    0.265
    (59.8)
    Naloxone
    0.0287
    (62.7)
    0.0773
    (159)
    0.323
    (28.7)
    0.0361
    (83.8)
    0.0286
    (68.1)
    Naloxone-3-β-D-Glucuronide
    9.02
    (29.8)
    9.03
    (21.8)
    6.75
    (40.0)
    6.80
    (14.7)
    8.12
    (30.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 120.02
    Confidence Interval (2-Sided) 90%
    83.35 to 172.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 107.85
    Confidence Interval (2-Sided) 90%
    75.85 to 153.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 171.76
    Confidence Interval (2-Sided) 90%
    117.93 to 250.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 112.82
    Confidence Interval (2-Sided) 90%
    77.66 to 163.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 106.38
    Confidence Interval (2-Sided) 90%
    71.43 to 158.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 95.59
    Confidence Interval (2-Sided) 90%
    64.36 to 141.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 152.24
    Confidence Interval (2-Sided) 90%
    103.08 to 224.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 135.17
    Confidence Interval (2-Sided) 90%
    75.44 to 242.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 67.87
    Confidence Interval (2-Sided) 90%
    38.82 to 118.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 48.39
    Confidence Interval (2-Sided) 90%
    27.01 to 86.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 76.59
    Confidence Interval (2-Sided) 90%
    42.75 to 137.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 176.48
    Confidence Interval (2-Sided) 90%
    94.62 to 329.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 88.62
    Confidence Interval (2-Sided) 90%
    48.60 to 161.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 63.17
    Confidence Interval (2-Sided) 90%
    33.87 to 117.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 100.41
    Confidence Interval (2-Sided) 90%
    51.30 to 196.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 270.00
    Confidence Interval (2-Sided) 90%
    141.86 to 513.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 1129.81
    Confidence Interval (2-Sided) 90%
    577.22 to 2211.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 126.25
    Confidence Interval (2-Sided) 90%
    64.50 to 247.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 79.53
    Confidence Interval (2-Sided) 90%
    38.79 to 163.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 213.86
    Confidence Interval (2-Sided) 90%
    107.07 to 427.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 894.91
    Confidence Interval (2-Sided) 90%
    436.49 to 1834.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 111.03
    Confidence Interval (2-Sided) 90%
    85.94 to 143.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 111.22
    Confidence Interval (2-Sided) 90%
    87.02 to 142.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 83.09
    Confidence Interval (2-Sided) 90%
    64.32 to 107.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 83.66
    Confidence Interval (2-Sided) 90%
    64.75 to 108.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 132.72
    Confidence Interval (2-Sided) 90%
    100.93 to 174.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 132.95
    Confidence Interval (2-Sided) 90%
    102.12 to 173.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 99.33
    Confidence Interval (2-Sided) 90%
    75.54 to 130.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description The extrapolation to infinity was done using the terminal phase. AUC0-inf = AUC0-last + Ct/λz Where Ct was the last observed quantifiable concentration and λz was the apparent terminal phase elimination rate constant.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (5,4,5,3,6)
    11.0
    (30.8)
    18.9
    (58.4)
    25.5
    (44.6)
    8.61
    (22.6)
    10.3
    (56.0)
    Norbuprenorphine (3,3,1,3,3)
    25.4
    (25.5)
    17.1
    (77.4)
    6.67
    (NA)
    13.9
    (58.6)
    16.0
    (23.0)
    Naloxone (5,6,5,4,7)
    0.0671
    (18.7)
    0.274
    (195)
    1.45
    (57.0)
    0.0851
    (57.0)
    0.0971
    (53.4)
    Naloxone-3-β-D-Glucuronide (5,7,6,5,4)
    21.9
    (28.0)
    28.9
    (32.7)
    21.3
    (38.5)
    21.5
    (15.0)
    26.0
    (12.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 125.19
    Confidence Interval (2-Sided) 90%
    79.46 to 197.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 220.97
    Confidence Interval (2-Sided) 90%
    135.33 to 360.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 249.28
    Confidence Interval (2-Sided) 90%
    162.19 to 383.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 94.44
    Confidence Interval (2-Sided) 90%
    56.44 to 158.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 132.57
    Confidence Interval (2-Sided) 90%
    78.86 to 222.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 233.99
    Confidence Interval (2-Sided) 90%
    135.63 to 403.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Buprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 263.97
    Confidence Interval (2-Sided) 90%
    155.52 to 448.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 159.38
    Confidence Interval (2-Sided) 90%
    78.21 to 324.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 106.93
    Confidence Interval (2-Sided) 90%
    52.47 to 217.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 87.10
    Confidence Interval (2-Sided) 90%
    42.74 to 177.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 182.98
    Confidence Interval (2-Sided) 90%
    89.79 to 372.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Norbuprenorphine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 122.77
    Confidence Interval (2-Sided) 90%
    60.24 to 250.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 69.12
    Confidence Interval (2-Sided) 90%
    33.45 to 142.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 282.17
    Confidence Interval (2-Sided) 90%
    141.59 to 562.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 1497.70
    Confidence Interval (2-Sided) 90%
    724.85 to 3094.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 87.64
    Confidence Interval (2-Sided) 90%
    40.30 to 190.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 78.86
    Confidence Interval (2-Sided) 90%
    34.34 to 181.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 321.94
    Confidence Interval (2-Sided) 90%
    144.65 to 716.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 1708.83
    Confidence Interval (2-Sided) 90%
    744.08 to 3924.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 84.20
    Confidence Interval (2-Sided) 90%
    60.92 to 116.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 110.98
    Confidence Interval (2-Sided) 90%
    82.02 to 150.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 81.97
    Confidence Interval (2-Sided) 90%
    60.03 to 111.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection HCV Without Hepatic Impairment, No Hepatic Disease or Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 82.78
    Confidence Interval (2-Sided) 90%
    59.89 to 114.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh A, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 101.71
    Confidence Interval (2-Sided) 90%
    74.96 to 138.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh B, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 134.06
    Confidence Interval (2-Sided) 90%
    101.07 to 177.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Hepatic Impairment: Child-Pugh C, HCV Without Hepatic Impairment
    Comments Naloxone-3-β-D-Glucuronide
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ratio of parameter means, %
    Estimated Value 99.02
    Confidence Interval (2-Sided) 90%
    73.93 to 132.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    Title Time to Reach the Maximum Plasma Concentration (Tmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine
    1.25
    1.50
    1.00
    1.38
    1.75
    Norbuprenorphine
    1.25
    1.25
    0.875
    1.00
    1.00
    Naloxone
    0.875
    0.750
    0.750
    1.00
    1.13
    Naloxone-3-β-D-Glucuronide
    0.500
    0.750
    0.500
    0.750
    0.500
    5. Primary Outcome
    Title Time of the Last Measureable Plasma Concentration (Tlast) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine
    72.0
    120
    168
    71.5
    96.0
    Norbuprenorphine
    144
    120
    48.0
    144
    156
    Naloxone
    10.0
    24.0
    24.0
    10.0
    10.0
    Naloxone-3-β-D-Glucuronide
    24.0
    24.1
    24.0
    36.0
    36.0
    6. Primary Outcome
    Title Percentage of Area Under the Concentration-time Curve From Time Zero to Infinity Due to Extrapolation (%AUCextrap) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description Calculated as: (AUC0-inf - AUC0-last)/AUC0-inf * 100 AUC0-inf, apparent body clearance (CL/F), and apparent volume of distribution during terminal phase (Vz/F) would not have been reported if %AUCextrap was > 20%.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (6,5,5,5,7)
    17.2
    (10.8)
    17.1
    (6.68)
    14.2
    (3.00)
    17.6
    (4.96)
    15.5
    (5.00)
    Norbuprenorphine (4,6,5,4,4)
    10.2
    (8.67)
    24.3
    (12.4)
    36.1
    (18.0)
    16.5
    (3.85)
    13.1
    (9.24)
    Naloxone (5,6,5,4,7)
    6.59
    (1.86)
    7.48
    (6.18)
    1.30
    (0.958)
    5.16
    (5.01)
    5.31
    (2.51)
    Naloxone-3-β-D-Glucuronide (5,7,6,5,4)
    4.98
    (1.74)
    3.34
    (1.53)
    3.50
    (2.08)
    6.04
    (3.60)
    5.13
    (3.55)
    7. Primary Outcome
    Title Terminal Phase Elimination Rate-Constant (λz) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description For the determination of λz, only those data points judged to describe the terminal log-linear decline resulting in an adjusted coefficient of determination value (R2) > 0.7 were used in the regression. A minimum of 3 data points were used in calculating λz.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (6,5,5,5,7)
    0.0221
    (46.0)
    0.0142
    (41.0)
    0.0123
    (29.5)
    0.0197
    (32.6)
    0.0193
    (50.2)
    Norbuprenorphine (4,6,5,4,4)
    0.0168
    (39.4)
    0.0131
    (21.5)
    0.0189
    (37.4)
    0.0135
    (7.37)
    0.0167
    (36.0)
    Naloxone (5,6,5,4,7)
    0.322
    (23.0)
    0.127
    (53.6)
    0.151
    (28.2)
    0.371
    (35.6)
    0.337
    (35.6)
    Naloxone-3-β-D-Glucuronide (5,7,6,5,4)
    0.0974
    (26.0)
    0.117
    (32.5)
    0.152
    (40.4)
    0.0637
    (41.9)
    0.0937
    (69.4)
    8. Primary Outcome
    Title Terminal Elimination Half-life (t1/2) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
    Description Terminal elimination half-life, calculated as ln(2)/λz. The terminal phase elimination half-life was calculated over a period of at least 2 half-lives.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (6,5,5,5,7)
    31.4
    (46.0)
    48.7
    (41.0)
    56.4
    (29.5)
    35.2
    (32.6)
    36.0
    (50.2)
    Norbuprenorphine (4,6,5,4,4)
    41.3
    (39.4)
    52.9
    (21.5)
    36.7
    (37.4)
    51.2
    (7.37)
    41.4
    (36.0)
    Naloxone (5,6,5,4,7)
    2.15
    (23.0)
    5.45
    (53.6)
    4.58
    (28.2)
    1.87
    (35.6)
    2.06
    (35.6)
    Naloxone-3-β-D-Glucuronide (5,7,6,5,4)
    7.12
    (26.0)
    5.91
    (32.5)
    4.55
    (40.4)
    10.9
    (41.9)
    7.40
    (69.4)
    9. Primary Outcome
    Title Apparent Body Clearance (CL/F) of Buprenorphine and Naloxone
    Description Apparent body clearance (only for buprenorphine and naloxone), calculated as Dose/AUC0-inf.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (5,4,5,3,6)
    182
    (30.8)
    106
    (58.4)
    78.3
    (44.6)
    232
    (22.6)
    193
    (56.0)
    Naloxone (5,6,5,4,7)
    7448
    (18.7)
    1824
    (195)
    344
    (57.0)
    5874
    (57.0)
    5148
    (53.4)
    10. Primary Outcome
    Title Apparent Volume of Distribution During Terminal Phase (Vz/F) of Buprenorphine and Naloxone
    Description Apparent volume of distribution during terminal phase (only for buprenorphine and naloxone), calculated as Dose/(λz • AUC0-inf).
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The PK population included participants without any major protocol deviations who contributed PK samples and had sufficient evaluable data for the calculation of PK parameters. Eight enrolled participants were excluded due to emesis observed within 4 hours postdose, and two due to protocol violations.
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    Measure Participants 6 7 6 6 8
    Buprenorphine (5,4,5,3,6)
    7226
    (26.1)
    6959
    (42.6)
    6373
    (28.9)
    9580
    (29.1)
    9176
    (21.9)
    Naloxone (5,6,5,4,7)
    23150
    (28.1)
    14353
    (187)
    2272
    (66.7)
    15845
    (97.9)
    15294
    (42.8)

    Adverse Events

    Time Frame Days 1 - 21
    Adverse Event Reporting Description
    Arm/Group Title Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Arm/Group Description 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. 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. 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. 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. Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1.
    All Cause Mortality
    Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    Other (Not Including Serious) Adverse Events
    Hepatic Impairment: Child-Pugh A Hepatic Impairment: Child-Pugh B Hepatic Impairment: Child-Pugh C HCV Without Hepatic Impairment No Hepatic Disease or Impairment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/9 (88.9%) 7/8 (87.5%) 6/8 (75%) 10/10 (100%) 8/8 (100%)
    Gastrointestinal disorders
    Vomiting 4/9 (44.4%) 1/8 (12.5%) 0/8 (0%) 5/10 (50%) 3/8 (37.5%)
    Nausea 5/9 (55.6%) 2/8 (25%) 0/8 (0%) 2/10 (20%) 3/8 (37.5%)
    Dry mouth 1/9 (11.1%) 3/8 (37.5%) 2/8 (25%) 2/10 (20%) 3/8 (37.5%)
    Constipation 1/9 (11.1%) 0/8 (0%) 1/8 (12.5%) 2/10 (20%) 1/8 (12.5%)
    Abdominal pain upper 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    Dyspepsia 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    Flatulence 1/9 (11.1%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    General disorders
    Fatigue 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 5/10 (50%) 3/8 (37.5%)
    Chills 1/9 (11.1%) 1/8 (12.5%) 0/8 (0%) 1/10 (10%) 0/8 (0%)
    Nervous system disorders
    Dizziness 5/9 (55.6%) 2/8 (25%) 4/8 (50%) 4/10 (40%) 5/8 (62.5%)
    Somnolence 3/9 (33.3%) 1/8 (12.5%) 1/8 (12.5%) 1/10 (10%) 3/8 (37.5%)
    Headache 1/9 (11.1%) 2/8 (25%) 0/8 (0%) 2/10 (20%) 0/8 (0%)
    Dysarthria 1/9 (11.1%) 1/8 (12.5%) 1/8 (12.5%) 0/10 (0%) 1/8 (12.5%)
    Dizziness postural 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 1/10 (10%) 0/8 (0%)
    Asterixis 0/9 (0%) 0/8 (0%) 1/8 (12.5%) 0/10 (0%) 0/8 (0%)
    Hepatic encephalopathy 0/9 (0%) 0/8 (0%) 1/8 (12.5%) 0/10 (0%) 0/8 (0%)
    Hypersomnia 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    Mental impairment 0/9 (0%) 1/8 (12.5%) 0/8 (0%) 0/10 (0%) 0/8 (0%)
    Sedation 0/9 (0%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 1/8 (12.5%)
    Psychiatric disorders
    Euphoric mood 1/9 (11.1%) 2/8 (25%) 4/8 (50%) 1/10 (10%) 0/8 (0%)
    Restlessness 0/9 (0%) 0/8 (0%) 1/8 (12.5%) 0/10 (0%) 0/8 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus 3/9 (33.3%) 1/8 (12.5%) 4/8 (50%) 1/10 (10%) 1/8 (12.5%)
    Dry skin 0/9 (0%) 0/8 (0%) 0/8 (0%) 1/10 (10%) 0/8 (0%)
    Hyperhidrosis 1/9 (11.1%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 0/8 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Reckitt Benckiser Pharmaceuticals, Inc.
    Organization RECKITT BENCKISER PHARMACEUTICALS, INC.
    Phone 804-379-1090
    Email
    Responsible Party:
    Indivior Inc.
    ClinicalTrials.gov Identifier:
    NCT01846455
    Other Study ID Numbers:
    • RB-US-08-0003
    First Posted:
    May 3, 2013
    Last Update Posted:
    Oct 24, 2016
    Last Verified:
    Sep 1, 2016