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| ID | Type | Description | Link |
|---|---|---|---|
| MK-1439-019 | Other Identifier | Merck Protocol Number |
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This study aimed to investigate the influence of hepatic insufficiency on the pharmacokinetics (PK) of doravirine (MK-1439). In Part 1, PK of doravirine in participants with moderate hepatic insufficiency was compared with that of healthy control subjects matched with regard to mean age and weight. If a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1, study Part 2 was to evaluate PK of doravirine in participants with mild hepatic insufficiency.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Moderate Hepatic Insufficiency | Experimental | Participants with moderate hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale. |
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| Part 1: Healthy Matched Control | Experimental | Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. |
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| Part 2: Mild Hepatic Insufficiency | Experimental | Participants with mild hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doravirine | Drug | Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency |
| Maximum Observed Plasma Concentration (Cmax) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency |
| Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose |
| Plasma Concentration of Doravirine at 24 Hours (C24) | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | 24 hours postdose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28026013 | Result | Khalilieh S, Yee KL, Liu R, Fan L, Sanchez RI, Auger P, Triantafyllou I, Stypinski D, Lasseter KC, Marbury T, Iwamoto M. Moderate Hepatic Impairment Does Not Affect Doravirine Pharmacokinetics. J Clin Pharmacol. 2017 Jun;57(6):777-783. doi: 10.1002/jcph.857. Epub 2016 Dec 27. |
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Part 2 of the study was to enroll participants only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. Because this was not observed, no participants were enrolled in Part 2 of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Participants With Moderate Hepatic Insufficiency | Participants with moderate hepatic insufficiency received a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale. |
| FG001 | Part 1: Healthy Control Participants | Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1. |
| FG002 | Part 2: Participants With Mild Hepatic Insufficiency | Participants with mild hepatic insufficiency received a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All enrolled participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Participants With Moderate Hepatic Insufficiency | Participants with moderate hepatic insufficiency received a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| 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 Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency |
|
Up to 14 days after drug administration
The population analyzed was all participants who received at least 1 dose of study treatment.
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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 | Part 1: Participants With Moderate Hepatic Insufficiency | Participants with moderate hepatic insufficiency received a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry mouth | Gastrointestinal disorders | MedDRA version 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| C000592662 | doravirine |
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| Part 1: Healthy Control Participants |
Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1. |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Child-Pugh Total Score | The Child-Pugh scale was used to classify the severity of liver disease in study participants. The total score is the sum of the scores on 5 clinical measures of liver disease, each on a 3-point scale where 3 is greatest severity: total bilirubin, serum albumin, INR, ascites, and hepatic encephalopathy. The total Child-Pugh score ranges from 5 to 15, where a score of 7 to 9 represents moderate hepatic insufficiency. | All enrolled participants. Healthy participants were not evaluated for Child-Pugh scores. | Count of Participants | Participants |
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| Weight | Mean | Full Range | kg |
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| OG001 | Part 1: Healthy Control Participants | Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1. |
|
|
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Geometric Mean | 95% Confidence Interval | nM | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours postdose for all participants and at 96, 120, and 144 hours postdose for participants with hepatic insufficiency |
|
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve Form 0 to 24 Hours (AUC0-24) of Doravirine | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours postdose |
|
|
|
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| Primary | Plasma Concentration of Doravirine at 24 Hours (C24) | Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method | The analysis population consisted of the subset of participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Geometric Mean | 95% Confidence Interval | nM | 24 hours postdose |
|
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| 0 |
| 8 |
| 0 |
| 8 |
| 4 |
| 8 |
| EG001 | Part 1: Healthy Control Participants | Healthy participants matched for age and weight received a single oral dose of 100 mg doravirine on Day 1 of Part 1. | 0 | 8 | 0 | 8 | 3 | 8 |
| Vomiting | Gastrointestinal disorders | MedDRA version 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.0 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDRA version 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 17.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA version 17.0 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
| Total Score = 9 |
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