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| Name | Class |
|---|---|
| Syneos Health | OTHER |
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This research study will evaluate the effect of hepatic impairment on the pharmacokinetics (the breakdown of the drug in the body) of parallel-group, multiple oral doses nalbuphine extended release (NAL ER), tablets in people with hepatic impairment (mild, moderate and severe), compared to people with normal liver function. The study will also test the safety and tolerability of the NAL ER, when it is given to participants with mild, moderate and severe hepatic impairment, compared to participants with normal liver function. This protocol will also study the effects of this drug on itching in hepatic impairment participants if they report some itching prior to taking part in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Single Ascending Dose | Experimental | Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose ranging from 27 mg up to 162 mg of NAL ER tablet under fasting conditions. There was a washout period of at least 7 days between the drug administration between each dose level. Participants with no hepatic impairment (group 4) received a single dose of NAL ER of up to 162 mg under fasting conditions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nalbuphine ER | Drug | Oral tablet |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Maximum Observed Plasma Concentration (Cmax) of NAL ER | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level | |
| Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of NAL ER | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level | |
| Part 1: Terminal Elimination Half-Life (T1/2 el) of NAL ER | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level | |
| Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of NAL ER | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level | |
| Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of NAL ER | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level | |
| Part 1: Number of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE) | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. | From signing the informed consent form up to Day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: Change From Baseline in Worst Itch Numerical Rating Scale (WI-NRS) | WI-NRS measure was used determine the severity of itch experienced by participants with hepatic impairment (for Cohort 6 only) at screening. Participants were to complete the two forms (the "Night-time Itch" and the "Daytime Itch") at the same time during the screening visit and the average was taken to determine the baseline severity. The scale was a 0 to 10 rating scale with 10 being the most severe itch experienced and 0 being no itching experienced. Higher score indicated greater severity of itching. |
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Inclusion Criteria:
For participants with Hepatic Impairment (Cohort 1 to 4 and Cohort 6):
For Healthy participants (Cohort 5):
Male or female, non-smoker and/or light smoker (up to 5 cigarettes or equivalent/day)
Healthy as defined by:
Exclusion Criteria:
For participants with Hepatic Impairment (Cohort 1 to 4 and Cohort 6):
For Healthy participants (Cohort 5):
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| Name | Affiliation | Role |
|---|---|---|
| Chief Development Officer | Trevi Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 01 | Miami | Florida | 33136 | United States | ||
| 02 |
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A total of 66 participants were screened and 28 participants were enrolled. The study was planned to be conducted in 2 parts: Part 1 (Single Ascending Dose [SAD]) followed by Part 2 (Multiple Ascending Dose [MAD]). As per the judgement of the safety committee, Part 2 was not conducted based on protocol defined criteria. In Part 1, each cohort was dosed sequentially from lowest dose for mild and moderate impaired participants. Participants in Cohort 1 could also take part in Cohorts 2, 3, and 4.
Participants were enrolled at 3 sites in the United States from 12 June 2019 to 05 February 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: NAL ER 27 mg | Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose of 27 mg of NAL ER tablet on Day 1 under fasting conditions. |
| FG001 | Cohort 2: NAL ER 54 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 54 mg of NAL ER tablet on Day 1 under fasting conditions. |
| FG002 | Cohort 3: NAL ER 108 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 108 mg of NAL ER tablet on Day 1 under fasting conditions. |
| FG003 | Cohort 4: NAL ER 162 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 162 mg of NAL ER tablet on Day 1 under fasting conditions. |
| FG004 | Cohort 5: NAL ER 162 mg | Healthy participants with normal hepatic function (group 4) received up to 162 mg of NAL ER tablet on Day 1 under fasting conditions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cohort 1 |
| |||||||||||||
| Cohort 2 |
| |||||||||||||
| Cohort 3 |
| |||||||||||||
| Cohorts 4 and 5 |
|
Safety analysis set (SAS) included all enrolled participants who had received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: All Participants | Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose ranging from 27 mg up to 162 mg of NAL ER tablet under fasting conditions within Cohorts 1, 2, 3, 4, and 5. There was a washout period of at least 7 days between the drug administration between each dose level. Participants with no hepatic impairment (group 4) received a single dose of NAL ER of up to 162 mg under fasting conditions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Participants in Cohort 1 in Part 1 of the study could also take part in Cohorts 2, 3, and 4. |
| 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 | Part 1: Maximum Observed Plasma Concentration (Cmax) of NAL ER | PK population consisted of all participants in the safety population for whom the PK profile could be adequately characterized. Number analyzed indicates number of participants who were evaluable for this outcome measure in a particular group. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level |
|
From the time of signing informed consent form to Day 4
SAS included all enrolled participants who had received at least 1 dose of study drug.
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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 | Cohort 1: NAL ER 27 mg | Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose of 27 mg of NAL ER tablet on Day 1 under fasting conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | Medra 22.0 | Systematic Assessment |
As per the judgement of the safety committee, the Part 2 (MAD) was not conducted based on protocol defined criteria.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Development Officer | Trevi Therapeutics, Inc. | 203-304-2499 | info@trevitherapeutics.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 5, 2019 | Jul 2, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 21, 2020 | Jul 2, 2025 | SAP_001.pdf |
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| Part 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | The clinical laboratory parameters included the clinical chemistry, hematology, coagulation, and urinalysis. Clinical significance was determined by the investigator. | From signing the informed consent form up to Day 4 |
| Part 1: Number of Participants With Clinically Significant Findings in Vital Sign Parameters | Vital signs measurements included diastolic and systolic blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator. | From signing the informed consent form up to Day 4 |
| Part 1: Number of Participants With Clinically Significant Findings in Physical Examination Parameters | Physical examination included examination of at least the following components: head, eyes, ears, nose, throat (HEENT), neck, lungs, abdomen, skin, cardiovascular and musculoskeletal evaluation, and general neurological examination. Clinical significance was determined by the investigator. | From signing the informed consent form up to Day 4 |
| Part 1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) | ECG data included the measurement of heart rate and aggregate PR interval, QRS duration, QT interval, QTcB interval, and QTcF interval. | From signing the informed consent form up to Day 4 |
| Part 1: Number of Participants With Clinically Significant Findings in Pulse Oximetry | Oxygen saturation was measured via pulse oximetry. Pulse oximetry measurements were to be collected within 10 min before or after the specified time point. Clinical significance was determined by the investigator. | Pre-dose and 1.5, 4, 5, and 8 hours post-dose in each dose level |
| Baseline, Day 16 |
| Miami |
| Florida |
| 33146 |
| United States |
| 03 | Orlando | Florida | 32809 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Participants in Cohort 1 in Part 1 of the study could also take part in Cohorts 2, 3, and 4. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Participants in Cohort 1 in Part 1 of the study could also take part in Cohorts 2, 3, and 4. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Participants in Cohort 1 in Part 1 of the study could also take part in Cohorts 2, 3, and 4. | Count of Participants | Participants |
|
Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 54 mg of NAL ER tablet on Day 1 under fasting conditions.
| OG002 | Cohort 3: NAL ER 108 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 108 mg of NAL ER tablet on Day 1 under fasting conditions. |
| OG003 | Cohort 4: NAL ER 162 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 108 mg of NAL ER tablet on Day 1 under fasting conditions. |
| OG004 | Cohort 5: NAL ER 162 mg | Healthy participants with normal hepatic function (group 4) received up to 162 mg of NAL ER tablet on Day 1 under fasting conditions. |
|
|
| Primary | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of NAL ER | PK population consisted of all participants in the safety population for whom the PK profile could be adequately characterized. Number analyzed indicates number of participants who were evaluable for this outcome measure in a particular group. | Posted | Median | Full Range | hours (h) | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level |
|
|
|
| Primary | Part 1: Terminal Elimination Half-Life (T1/2 el) of NAL ER | PK population consisted of all participants in the safety population for whom the PK profile could be adequately characterized. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed indicates number of participants who were evaluable in a particular group. | Posted | Median | Full Range | h | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level |
|
|
|
| Primary | Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of NAL ER | PK population consisted of all participants in the safety population for whom the PK profile could be adequately characterized. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed indicates number of participants who were evaluable in a particular group. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour-nanogram per milliliter (h*ng/mL) | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level |
|
|
|
| Primary | Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of NAL ER | PK population consisted of all participants in the safety population for whom the PK profile could be adequately characterized. Number analyzed indicates number of participants who were evaluable for this outcome measure in a particular group. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level |
|
|
|
| Primary | Part 1: Number of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE) | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. | Safety analysis set (SAS) included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From signing the informed consent form up to Day 4 |
|
|
|
| Primary | Part 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | The clinical laboratory parameters included the clinical chemistry, hematology, coagulation, and urinalysis. Clinical significance was determined by the investigator. | SAS included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From signing the informed consent form up to Day 4 |
|
|
|
| Primary | Part 1: Number of Participants With Clinically Significant Findings in Vital Sign Parameters | Vital signs measurements included diastolic and systolic blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator. | SAS included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From signing the informed consent form up to Day 4 |
|
|
|
| Primary | Part 1: Number of Participants With Clinically Significant Findings in Physical Examination Parameters | Physical examination included examination of at least the following components: head, eyes, ears, nose, throat (HEENT), neck, lungs, abdomen, skin, cardiovascular and musculoskeletal evaluation, and general neurological examination. Clinical significance was determined by the investigator. | SAS included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From signing the informed consent form up to Day 4 |
|
|
|
| Primary | Part 1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) | ECG data included the measurement of heart rate and aggregate PR interval, QRS duration, QT interval, QTcB interval, and QTcF interval. | SAS included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From signing the informed consent form up to Day 4 |
|
|
|
| Primary | Part 1: Number of Participants With Clinically Significant Findings in Pulse Oximetry | Oxygen saturation was measured via pulse oximetry. Pulse oximetry measurements were to be collected within 10 min before or after the specified time point. Clinical significance was determined by the investigator. | SAS included all enrolled participants who had received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Pre-dose and 1.5, 4, 5, and 8 hours post-dose in each dose level |
|
|
|
| Secondary | Part 2: Change From Baseline in Worst Itch Numerical Rating Scale (WI-NRS) | WI-NRS measure was used determine the severity of itch experienced by participants with hepatic impairment (for Cohort 6 only) at screening. Participants were to complete the two forms (the "Night-time Itch" and the "Daytime Itch") at the same time during the screening visit and the average was taken to determine the baseline severity. The scale was a 0 to 10 rating scale with 10 being the most severe itch experienced and 0 being no itching experienced. Higher score indicated greater severity of itching. | As per the judgement of the safety committee, the Part 2 (MAD) was not conducted based on protocol defined criteria. Hence, this outcome was not assessed as Part 2 of the study was not conducted. | Posted | Baseline, Day 16 |
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 3 |
| 16 |
| EG001 | Cohort 2: NAL ER 54 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 54 mg of NAL ER tablet on Day 1 under fasting conditions. | 0 | 15 | 0 | 15 | 5 | 15 |
| EG002 | Cohort 3: NAL ER 108 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 108 mg of NAL ER tablet on Day 1 under fasting conditions. | 0 | 15 | 0 | 15 | 9 | 15 |
| EG003 | Cohort 4: NAL ER 162 mg | Participants with mild (group 1) and moderate (group 2) hepatic impairment received single dose of 162 mg of NAL ER tablet on Day 1 under fasting conditions. | 0 | 13 | 0 | 13 | 12 | 13 |
| EG004 | Cohort 5: NAL ER 162 mg | Healthy participants with normal hepatic function (group 4) received up to 162 mg of NAL ER tablet on Day 1 under fasting conditions. | 0 | 8 | 0 | 8 | 5 | 8 |
| Nausea | Gastrointestinal disorders | Medra 22.0 | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | Medra 22.0 | Systematic Assessment |
|
| Euphoric Mood | Psychiatric disorders | Medra 22.0 | Systematic Assessment |
|
| Feeling of Relaxation | General disorders | Medra 22.0 | Systematic Assessment |
|
| Malaise | General disorders | Medra 22.0 | Systematic Assessment |
|
| Ventricular arrhythmia | Cardiac disorders | Medra 22.0 | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Medra 22.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | Medra 22.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Medra 22.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Medra 22.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | Medra 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | Medra 22.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Medra 22.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Medra 22.0 | Systematic Assessment |
|
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|
|
|
|
|
|
|
|
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
| Moderate Hepatic Impairment (Group 2) |
|
|
| Severe Hepatic Impairment (Group 3) |
|
|
| No Hepatic Impairment (Group 4) |
|
|
|
| Moderate Hepatic Impairment (Group 2) |
|
|
| Severe Hepatic Impairment (Group 3) |
|
|
| No Hepatic Impairment (Group 4) |
|
|
|
| Moderate Hepatic Impairment (Group 2) |
|
|
| Severe Hepatic Impairment (Group 3) |
|
|
| No Hepatic Impairment (Group 4) |
|
|
|
| Moderate Hepatic Impairment (Group 2) |
|
|
| Severe Hepatic Impairment (Group 3) |
|
|
| No Hepatic Impairment (Group 4) |
|
|