Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 45 of 186 for:    BUPRENORPHINE AND NALOXONE

Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01846455
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : October 24, 2016
Last Update Posted : October 24, 2016
Sponsor:
Information provided by (Responsible Party):
Indivior Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hepatic Failure
Hepatic Impairment
Chronic Hepatitis C Infection With Hepatic Coma
Interventions Drug: 2.0mg Buprenorphine/0.5mg Naloxone
Drug: Promethazine
Enrollment 43
Recruitment Details  
Pre-assignment Details  
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
Hide 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
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
Hide 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 Number of Baseline Participants 9 8 8 10 8 43
Hide Baseline Analysis Population Description
Safety population
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants 8 participants 8 participants 10 participants 8 participants 43 participants
58.0
(51 to 62)
58.6
(52 to 63)
53.9
(42 to 65)
53.0
(43 to 59)
57.1
(49 to 62)
56.0
(42 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 8 participants 10 participants 8 participants 43 participants
Female
3
  33.3%
4
  50.0%
1
  12.5%
6
  60.0%
4
  50.0%
18
  41.9%
Male
6
  66.7%
4
  50.0%
7
  87.5%
4
  40.0%
4
  50.0%
25
  58.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 8 participants 10 participants 8 participants 43 participants
White 6 7 8 8 7 36
Black or African American 2 1 0 1 1 5
Asian 1 0 0 1 0 2
Weight  
Mean (Full Range)
Unit of measure:  Kg
Number Analyzed 9 participants 8 participants 8 participants 10 participants 8 participants 43 participants
74.2
(54.0 to 92.5)
75.4
(56.0 to 95.0)
82.2
(64.8 to 103.0)
74.7
(60.2 to 109.0)
76.6
(69.2 to 83.6)
76.5
(54.0 to 109.0)
Body Mass Index  
Mean (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 9 participants 8 participants 8 participants 10 participants 8 participants 43 participants
25.5
(18.7 to 32.8)
27.0
(20.3 to 32.3)
27.9
(23.2 to 32.8)
26.2
(20.6 to 32.9)
29.3
(22.1 to 32.2)
27.1
(18.7 to 32.9)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
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%)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 99.34
Confidence Interval (2-Sided) 90%
66.05 to 149.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 163.88
Confidence Interval (2-Sided) 90%
110.82 to 242.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 281.43
Confidence Interval (2-Sided) 90%
187.10 to 423.33
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 78.43
Confidence Interval (2-Sided) 90%
52.14 to 117.98
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 126.66
Confidence Interval (2-Sided) 90%
81.87 to 195.97
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 208.94
Confidence Interval (2-Sided) 90%
137.21 to 318.18
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 358.83
Confidence Interval (2-Sided) 90%
231.92 to 555.17
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 78.09
Confidence Interval (2-Sided) 90%
44.03 to 138.49
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 74.78
Confidence Interval (2-Sided) 90%
39.26 to 142.41
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 11.45
Confidence Interval (2-Sided) 90%
6.35 to 20.66
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 71.08
Confidence Interval (2-Sided) 90%
39.00 to 129.49
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 109.90
Confidence Interval (2-Sided) 90%
58.14 to 207.75
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 105.23
Confidence Interval (2-Sided) 90%
52.17 to 212.24
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 16.12
Confidence Interval (2-Sided) 90%
8.40 to 30.94
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 79.30
Confidence Interval (2-Sided) 90%
40.03 to 157.12
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 317.58
Confidence Interval (2-Sided) 90%
164.93 to 611.54
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 1401.85
Confidence Interval (2-Sided) 90%
707.55 to 2777.46
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 105.78
Confidence Interval (2-Sided) 90%
53.39 to 209.59
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 74.97
Confidence Interval (2-Sided) 90%
36.09 to 155.71
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 300.22
Confidence Interval (2-Sided) 90%
148.44 to 607.21
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 1325.22
Confidence Interval (2-Sided) 90%
638.03 to 2752.55
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 85.87
Confidence Interval (2-Sided) 90%
66.06 to 111.61
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 123.77
Confidence Interval (2-Sided) 90%
96.27 to 159.13
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 91.26
Confidence Interval (2-Sided) 90%
70.21 to 118.62
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 84.78
Confidence Interval (2-Sided) 90%
65.23 to 110.20
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 101.28
Confidence Interval (2-Sided) 90%
76.52 to 134.06
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 145.99
Confidence Interval (2-Sided) 90%
111.43 to 191.26
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 107.64
Confidence Interval (2-Sided) 90%
81.33 to 142.47
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
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%)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 120.02
Confidence Interval (2-Sided) 90%
83.35 to 172.82
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 107.85
Confidence Interval (2-Sided) 90%
75.85 to 153.36
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 171.76
Confidence Interval (2-Sided) 90%
117.93 to 250.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 112.82
Confidence Interval (2-Sided) 90%
77.66 to 163.91
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 106.38
Confidence Interval (2-Sided) 90%
71.43 to 158.43
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 95.59
Confidence Interval (2-Sided) 90%
64.36 to 141.99
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 152.24
Confidence Interval (2-Sided) 90%
103.08 to 224.83
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 135.17
Confidence Interval (2-Sided) 90%
75.44 to 242.16
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 67.87
Confidence Interval (2-Sided) 90%
38.82 to 118.68
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 48.39
Confidence Interval (2-Sided) 90%
27.01 to 86.69
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 76.59
Confidence Interval (2-Sided) 90%
42.75 to 137.22
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 176.48
Confidence Interval (2-Sided) 90%
94.62 to 329.17
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 88.62
Confidence Interval (2-Sided) 90%
48.60 to 161.59
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 63.17
Confidence Interval (2-Sided) 90%
33.87 to 117.83
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 100.41
Confidence Interval (2-Sided) 90%
51.30 to 196.53
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 270.00
Confidence Interval (2-Sided) 90%
141.86 to 513.90
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 1129.81
Confidence Interval (2-Sided) 90%
577.22 to 2211.44
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 126.25
Confidence Interval (2-Sided) 90%
64.50 to 247.11
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 79.53
Confidence Interval (2-Sided) 90%
38.79 to 163.06
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 213.86
Confidence Interval (2-Sided) 90%
107.07 to 427.17
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 894.91
Confidence Interval (2-Sided) 90%
436.49 to 1834.80
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 111.03
Confidence Interval (2-Sided) 90%
85.94 to 143.44
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 111.22
Confidence Interval (2-Sided) 90%
87.02 to 142.16
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 83.09
Confidence Interval (2-Sided) 90%
64.32 to 107.35
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 83.66
Confidence Interval (2-Sided) 90%
64.75 to 108.08
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 132.72
Confidence Interval (2-Sided) 90%
100.93 to 174.53
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 132.95
Confidence Interval (2-Sided) 90%
102.12 to 173.10
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 99.33
Confidence Interval (2-Sided) 90%
75.54 to 130.61
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
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 [1] 
(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%)
[1]
Value is for a single participant
Show Statistical Analysis 1 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 125.19
Confidence Interval (2-Sided) 90%
79.46 to 197.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 220.97
Confidence Interval (2-Sided) 90%
135.33 to 360.81
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 249.28
Confidence Interval (2-Sided) 90%
162.19 to 383.14
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 94.44
Confidence Interval (2-Sided) 90%
56.44 to 158.02
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 132.57
Confidence Interval (2-Sided) 90%
78.86 to 222.84
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 233.99
Confidence Interval (2-Sided) 90%
135.63 to 403.68
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 263.97
Confidence Interval (2-Sided) 90%
155.52 to 448.03
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 159.38
Confidence Interval (2-Sided) 90%
78.21 to 324.79
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 106.93
Confidence Interval (2-Sided) 90%
52.47 to 217.91
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 87.10
Confidence Interval (2-Sided) 90%
42.74 to 177.50
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 182.98
Confidence Interval (2-Sided) 90%
89.79 to 372.89
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 122.77
Confidence Interval (2-Sided) 90%
60.24 to 250.19
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 69.12
Confidence Interval (2-Sided) 90%
33.45 to 142.82
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 282.17
Confidence Interval (2-Sided) 90%
141.59 to 562.30
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 1497.70
Confidence Interval (2-Sided) 90%
724.85 to 3094.59
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 87.64
Confidence Interval (2-Sided) 90%
40.30 to 190.59
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 78.86
Confidence Interval (2-Sided) 90%
34.34 to 181.12
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 321.94
Confidence Interval (2-Sided) 90%
144.65 to 716.52
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 1708.83
Confidence Interval (2-Sided) 90%
744.08 to 3924.47
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 84.20
Confidence Interval (2-Sided) 90%
60.92 to 116.38
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 110.98
Confidence Interval (2-Sided) 90%
82.02 to 150.17
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 81.97
Confidence Interval (2-Sided) 90%
60.03 to 111.92
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 82.78
Confidence Interval (2-Sided) 90%
59.89 to 114.42
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 101.71
Confidence Interval (2-Sided) 90%
74.96 to 138.00
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 134.06
Confidence Interval (2-Sided) 90%
101.07 to 177.82
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide 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 [Not Specified]
Method of Estimation Estimation Parameter ratio of parameter means, %
Estimated Value 99.02
Confidence Interval (2-Sided) 90%
73.93 to 132.61
Estimation Comments [Not Specified]
4.Primary Outcome
Title Time to Reach the Maximum Plasma Concentration (Tmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Median (Full Range)
Unit of Measure: hours
Buprenorphine
1.25
(1.00 to 2.00)
1.50
(0.500 to 2.00)
1.00
(0.500 to 2.00)
1.38
(1.00 to 1.50)
1.75
(1.00 to 3.00)
Norbuprenorphine
1.25
(1.00 to 1.25)
1.25
(1.00 to 36.0)
0.875
(0.500 to 6.00)
1.00
(1.00 to 36.0)
1.00
(1.00 to 2.00)
Naloxone
0.875
(0.500 to 1.25)
0.750
(0.500 to 1.50)
0.750
(0.250 to 1.25)
1.00
(0.500 to 1.00)
1.13
(0.500 to 2.00)
Naloxone-3-β-D-Glucuronide
0.500
(0.500 to 1.00)
0.750
(0.500 to 0.750)
0.500
(0.500 to 0.767)
0.750
(0.750 to 1.00)
0.500
(0.500 to 1.50)
5.Primary Outcome
Title Time of the Last Measureable Plasma Concentration (Tlast) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Median (Full Range)
Unit of Measure: hours
Buprenorphine
72.0
(48.0 to 96.0)
120
(72.0 to 168)
168
(96.0 to 168)
71.5
(36.0 to 97.0)
96.0
(36.0 to 144)
Norbuprenorphine
144
(72.0 to 168)
120
(72.0 to 168)
48.0
(12.0 to 96.0)
144
(119 to 169)
156
(120 to 168)
Naloxone
10.0
(6.03 to 12.0)
24.0
(12.0 to 36.0)
24.0
(24.0 to 48.0)
10.0
(8.00 to 24.0)
10.0
(6.00 to 24.0)
Naloxone-3-β-D-Glucuronide
24.0
(12.0 to 36.0)
24.1
(12.0 to 36.0)
24.0
(12.0 to 36.0)
36.0
(24.0 to 36.0)
36.0
(24.0 to 72.0)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Mean (Standard Deviation)
Unit of Measure: percentage of AUC0-inf
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/hour
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7 6 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
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%)
Time Frame Days 1 - 21
Adverse Event Reporting Description [Not Specified]
 
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/8 (0.00%)   0/8 (0.00%)   0/10 (0.00%)   0/8 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/9 (88.89%)   7/8 (87.50%)   6/8 (75.00%)   10/10 (100.00%)   8/8 (100.00%) 
Gastrointestinal disorders           
Vomiting  1  4/9 (44.44%)  1/8 (12.50%)  0/8 (0.00%)  5/10 (50.00%)  3/8 (37.50%) 
Nausea  1  5/9 (55.56%)  2/8 (25.00%)  0/8 (0.00%)  2/10 (20.00%)  3/8 (37.50%) 
Dry mouth  1  1/9 (11.11%)  3/8 (37.50%)  2/8 (25.00%)  2/10 (20.00%)  3/8 (37.50%) 
Constipation  1  1/9 (11.11%)  0/8 (0.00%)  1/8 (12.50%)  2/10 (20.00%)  1/8 (12.50%) 
Abdominal pain upper  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
Dyspepsia  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
Flatulence  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
General disorders           
Fatigue  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  5/10 (50.00%)  3/8 (37.50%) 
Chills  1  1/9 (11.11%)  1/8 (12.50%)  0/8 (0.00%)  1/10 (10.00%)  0/8 (0.00%) 
Nervous system disorders           
Dizziness  1  5/9 (55.56%)  2/8 (25.00%)  4/8 (50.00%)  4/10 (40.00%)  5/8 (62.50%) 
Somnolence  1  3/9 (33.33%)  1/8 (12.50%)  1/8 (12.50%)  1/10 (10.00%)  3/8 (37.50%) 
Headache  1  1/9 (11.11%)  2/8 (25.00%)  0/8 (0.00%)  2/10 (20.00%)  0/8 (0.00%) 
Dysarthria  1  1/9 (11.11%)  1/8 (12.50%)  1/8 (12.50%)  0/10 (0.00%)  1/8 (12.50%) 
Dizziness postural  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  1/10 (10.00%)  0/8 (0.00%) 
Asterixis  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/10 (0.00%)  0/8 (0.00%) 
Hepatic encephalopathy  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/10 (0.00%)  0/8 (0.00%) 
Hypersomnia  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
Mental impairment  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
Sedation  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/10 (0.00%)  1/8 (12.50%) 
Psychiatric disorders           
Euphoric mood  1  1/9 (11.11%)  2/8 (25.00%)  4/8 (50.00%)  1/10 (10.00%)  0/8 (0.00%) 
Restlessness  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/10 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders           
Pruritus  1  3/9 (33.33%)  1/8 (12.50%)  4/8 (50.00%)  1/10 (10.00%)  1/8 (12.50%) 
Dry skin  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/10 (10.00%)  0/8 (0.00%) 
Hyperhidrosis  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/10 (0.00%)  0/8 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Reckitt Benckiser Pharmaceuticals, Inc.
Organization: RECKITT BENCKISER PHARMACEUTICALS, INC.
Phone: 804-379-1090
Layout table for additonal information
Responsible Party: Indivior Inc.
ClinicalTrials.gov Identifier: NCT01846455     History of Changes
Other Study ID Numbers: RB-US-08-0003
First Submitted: May 1, 2013
First Posted: May 3, 2013
Results First Submitted: August 7, 2015
Results First Posted: October 24, 2016
Last Update Posted: October 24, 2016