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The objective was to determine if hepatitis C virus (HCV) infection or mild to severe hepatic impairment (Child-Pugh Classes A, B, and C) altered the PK of buprenorphine, norbuprenorphine, or naloxone.
This will be a multi-center, open-label study. After providing informed consent, subjects will undergo an outpatient screening period of up to 21 days. Screening procedures will include an assessment of mental status which will be repeated before dosing. Eligible subjects will then undergo hospital intake procedures and reside at the investigational site until Day 5. Subjects will be enrolled in 5-treatment groups as follows: (1) Group 1: Subjects with hepatic impairment classified as Child-Pugh A; (2) Group 2: Subjects with hepatic impairment classified as Child-Pugh B; (3) Group 3: Subjects with hepatic impairment classified as Child-Pugh C; (4) Group 4: Subjects with Hepatitis C Virus (HCV) infection but without hepatic impairment; and (5) Group 5: Subjects without hepatic disease or impairment. Group 5 is used as a control group
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hepatic Impairment: Child-Pugh A | Experimental | 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. |
|
| Hepatic Impairment: Child-Pugh B | Experimental | 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. |
|
| Hepatic Impairment: Child-Pugh C | Experimental | 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. |
|
| HCV Without Hepatic Impairment | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2.0mg Buprenorphine/0.5mg Naloxone | Drug | Each participant received a single sublingual dose of Suboxone® on Day 1 following a fast of at least 8 hours prior to dosing and 2 hours after dosing. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 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 |
| 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 | |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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 |
| 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 | |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami, Inc. | Hialeah | Florida | 33014-3616 | United States | ||
| Orlando Clinical Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25603822 | Result | Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers. Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety population
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
|
Days 1 - 21
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Reckitt Benckiser Pharmaceuticals, Inc. | RECKITT BENCKISER PHARMACEUTICALS, INC. | 804-379-1090 |
Not provided
| ID | Term |
|---|---|
| D017093 | Liver Failure |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D000086982 | Blood-Borne Infections |
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Not provided
| ID | Term |
|---|---|
| D000069479 | Buprenorphine, Naloxone Drug Combination |
| D011398 | Promethazine |
| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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Not provided
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| No Hepatic Disease or Impairment | Active Comparator | Participants with no hepatic disease or impairment received one sublingual tablet of Suboxone® (2mg buprenorphine with 0.5 mg naloxone) on Day 1. |
|
|
| Promethazine | Drug | Each participant received a 25-mg or 50-mg promethazine oral dose 30 minutes before Suboxone® administration and then 25-mg promethazine orally or by rectal suppositories every 4 hours as needed for nausea and vomiting during the first 48 hours after Suboxone® administration. |
|
| 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 | 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%. | 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 Phase Elimination Rate-Constant (λz) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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 (t1/2) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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 (CL/F) of Buprenorphine and Naloxone | Apparent body clearance (only for buprenorphine and naloxone), calculated as Dose/AUC0-inf. | 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 (Vz/F) of Buprenorphine and Naloxone | Apparent volume of distribution during terminal phase (only for buprenorphine and naloxone), calculated as Dose/(λz • AUC0-inf). | 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 |
| Orlando |
| Florida |
| 32809 |
| United States |
| American Research Corporation (ARC) | San Antonio | Texas | 78215 | United States |
| 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Weight | Mean | Full Range | kg |
|
| Body Mass Index | Mean | Full Range | kg/m^2 |
|
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. |
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
|
|
|
|
| Primary | Time to Reach the Maximum Plasma Concentration (Tmax) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | Posted | Median | Full Range | hours | 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 |
|
|
|
| Primary | Time of the Last Measureable Plasma Concentration (Tlast) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | Posted | Median | Full Range | hours | 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 |
|
|
|
| Primary | 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 | 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%. | 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. | Posted | Mean | Standard Deviation | percentage of AUC0-inf | 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 |
|
|
|
| Primary | Terminal Phase Elimination Rate-Constant (λz) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hour | 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 |
|
|
|
| Primary | Terminal Elimination Half-life (t1/2) of Buprenorphine, Norbuprenorphine, Naloxone and Naloxone-3-β-D-Glucuronide | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 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 |
|
|
|
| Primary | Apparent Body Clearance (CL/F) of Buprenorphine and Naloxone | Apparent body clearance (only for buprenorphine and naloxone), calculated as Dose/AUC0-inf. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 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 |
|
|
|
| Primary | Apparent Volume of Distribution During Terminal Phase (Vz/F) of Buprenorphine and Naloxone | Apparent volume of distribution during terminal phase (only for buprenorphine and naloxone), calculated as Dose/(λz • AUC0-inf). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 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 |
|
|
|
| 0 |
| 9 |
| 8 |
| 9 |
| EG001 | 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. | 0 | 8 | 7 | 8 |
| EG002 | 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. | 0 | 8 | 6 | 8 |
| EG003 | 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. | 0 | 10 | 10 | 10 |
| EG004 | 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. | 0 | 8 | 8 | 8 |
| Somnolence | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Asterixis | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Mental impairment | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 15.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Euphoric mood | Psychiatric disorders | MedDRA 15.0 | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 15.0 | Systematic Assessment |
|
Not provided
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D006571 |
| Heterocyclic Compounds |
| D009270 | Naloxone |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D010640 | Phenothiazines |
| D013457 | Sulfur Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| Norbuprenorphine |
|
| Naloxone |
|
| Naloxone-3-β-D-Glucuronide |
|
| ratio of parameter means, % |
| 107.85 |
| 2-Sided |
| 90 |
| 75.85 |
| 153.36 |
| No |
| Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 171.76 | 2-Sided | 90 | 117.93 | 250.15 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 112.82 | 2-Sided | 90 | 77.66 | 163.91 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 106.38 | 2-Sided | 90 | 71.43 | 158.43 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 95.59 | 2-Sided | 90 | 64.36 | 141.99 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 152.24 | 2-Sided | 90 | 103.08 | 224.83 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 135.17 | 2-Sided | 90 | 75.44 | 242.16 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 67.87 | 2-Sided | 90 | 38.82 | 118.68 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 48.39 | 2-Sided | 90 | 27.01 | 86.69 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 76.59 | 2-Sided | 90 | 42.75 | 137.22 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 176.48 | 2-Sided | 90 | 94.62 | 329.17 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 88.62 | 2-Sided | 90 | 48.60 | 161.59 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 63.17 | 2-Sided | 90 | 33.87 | 117.83 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 100.41 | 2-Sided | 90 | 51.30 | 196.53 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 270.00 | 2-Sided | 90 | 141.86 | 513.90 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 1129.81 | 2-Sided | 90 | 577.22 | 2211.44 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 126.25 | 2-Sided | 90 | 64.50 | 247.11 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 79.53 | 2-Sided | 90 | 38.79 | 163.06 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 213.86 | 2-Sided | 90 | 107.07 | 427.17 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 894.91 | 2-Sided | 90 | 436.49 | 1834.80 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 111.03 | 2-Sided | 90 | 85.94 | 143.44 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 111.22 | 2-Sided | 90 | 87.02 | 142.16 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 83.09 | 2-Sided | 90 | 64.32 | 107.35 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 83.66 | 2-Sided | 90 | 64.75 | 108.08 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 132.72 | 2-Sided | 90 | 100.93 | 174.53 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 132.95 | 2-Sided | 90 | 102.12 | 173.10 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 99.33 | 2-Sided | 90 | 75.54 | 130.61 | No | Superiority or Other |
| Norbuprenorphine (3,3,1,3,3) |
|
| Naloxone (5,6,5,4,7) |
|
| Naloxone-3-β-D-Glucuronide (5,7,6,5,4) |
|
| ratio of parameter means, % |
| 220.97 |
| 2-Sided |
| 90 |
| 135.33 |
| 360.81 |
| No |
| Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 249.28 | 2-Sided | 90 | 162.19 | 383.14 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 94.44 | 2-Sided | 90 | 56.44 | 158.02 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 132.57 | 2-Sided | 90 | 78.86 | 222.84 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 233.99 | 2-Sided | 90 | 135.63 | 403.68 | No | Superiority or Other |
| Buprenorphine | ratio of parameter means, % | 263.97 | 2-Sided | 90 | 155.52 | 448.03 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 159.38 | 2-Sided | 90 | 78.21 | 324.79 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 106.93 | 2-Sided | 90 | 52.47 | 217.91 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 87.10 | 2-Sided | 90 | 42.74 | 177.50 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 182.98 | 2-Sided | 90 | 89.79 | 372.89 | No | Superiority or Other |
| Norbuprenorphine | ratio of parameter means, % | 122.77 | 2-Sided | 90 | 60.24 | 250.19 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 69.12 | 2-Sided | 90 | 33.45 | 142.82 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 282.17 | 2-Sided | 90 | 141.59 | 562.30 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 1497.70 | 2-Sided | 90 | 724.85 | 3094.59 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 87.64 | 2-Sided | 90 | 40.30 | 190.59 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 78.86 | 2-Sided | 90 | 34.34 | 181.12 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 321.94 | 2-Sided | 90 | 144.65 | 716.52 | No | Superiority or Other |
| Naloxone | ratio of parameter means, % | 1708.83 | 2-Sided | 90 | 744.08 | 3924.47 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 84.20 | 2-Sided | 90 | 60.92 | 116.38 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 110.98 | 2-Sided | 90 | 82.02 | 150.17 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 81.97 | 2-Sided | 90 | 60.03 | 111.92 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 82.78 | 2-Sided | 90 | 59.89 | 114.42 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 101.71 | 2-Sided | 90 | 74.96 | 138.00 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 134.06 | 2-Sided | 90 | 101.07 | 177.82 | No | Superiority or Other |
| Naloxone-3-β-D-Glucuronide | ratio of parameter means, % | 99.02 | 2-Sided | 90 | 73.93 | 132.61 | No | Superiority or Other |
| Norbuprenorphine |
|
| Naloxone |
|
| Naloxone-3-β-D-Glucuronide |
|
| Norbuprenorphine |
|
| Naloxone |
|
| Naloxone-3-β-D-Glucuronide |
|
| Norbuprenorphine (4,6,5,4,4) |
|
| Naloxone (5,6,5,4,7) |
|
| Naloxone-3-β-D-Glucuronide (5,7,6,5,4) |
|
| Norbuprenorphine (4,6,5,4,4) |
|
| Naloxone (5,6,5,4,7) |
|
| Naloxone-3-β-D-Glucuronide (5,7,6,5,4) |
|
| Norbuprenorphine (4,6,5,4,4) |
|
| Naloxone (5,6,5,4,7) |
|
| Naloxone-3-β-D-Glucuronide (5,7,6,5,4) |
|
| Naloxone (5,6,5,4,7) |
|
| Naloxone (5,6,5,4,7) |
|