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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3866-006 | Other Identifier | Merck Protocol Number |
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Business and program changes
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This is an open-label, single-dose, Phase 1 study to evaluate the pharmacokinetics (PK) of intravenous (IV) MK-3866 in participants with moderate and severe hepatic impairment (HI) compared to that of matched healthy participants. The primary purpose of this study is to understand the effect of HI on the plasma PK of MK-3866 in order to guide dosing recommendations for participants with HI. This study will also evaluate the safety and tolerability of MK-3866 in participants with moderate and severe HI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate Hepatic Impairment (Panel A) | Experimental | Participants with moderate HI (estimated glomerular filtration rate [eGFR] of ≤60mL/min/1.73m^2) receive a single IV dose of MK-3866 (150 mg) on Day 1. |
|
| Severe Hepatic Impairment (Panel B) | Experimental | Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) receive a single IV dose of MK-3866 (150 mg) on Day 1. |
|
| Healthy Matched Controls (Panel C) | Experimental | Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-3866 | Drug | Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞) | AUC0-∞ is determined for the period up to 72 hours post-single dose. AUC0-∞ is an estimate of total plasma exposure from dosing to (extrapolated) infinity. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last) | AUC0-last is determined for the period up to 72 hours post-single dose. AUC0-last is an estimate of total plasma exposure from dosing to the time of last measurable sample. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr) | AUC0-24 is determined for the period up to 24 hours post-single dose. AUC0-24 is an estimate of total daily plasma exposure from dosing to 24 hours postdose. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose |
| Concentration at the End of Infusion (Ceoi) of MK-3866 | The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi. | 0.5 (end of infusion) hours postdose |
| Time to Maximum Concentration (Tmax) of MK-3866 | Tmax is the time at which the maximum plasma drug concentration is detected. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Apparent Terminal Half-life (t1/2) of MK-3866 |
| Measure | Description | Time Frame |
|---|---|---|
| Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe) | Fe is the amount of drug excreted unchanged in urine. Urine samples were collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available. | Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami ( Site 0001) | Hialeah | Florida | 33014 | United States | ||
| Orlando Clinical Research Center ( Site 0002) |
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Participants with moderate or severe hepatic impairment (HI) based on estimated glomerular filtration rate (eGFR) were enrolled at 2 study centers in the US.
The study terminated prior to enrollment of any healthy control participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Moderate Hepatic Impairment (Panel A) | Participants with moderate HI (eGFR of ≤60mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. |
| FG001 | Severe Hepatic Impairment (Panel B) | Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Moderate Hepatic Impairment (Panel A) | Participants with moderate HI (eGFR of ≤60mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. |
| BG001 | Severe Hepatic Impairment (Panel B) |
| 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 of MK-3866 From Time 0 to Infinity (AUC0-∞) | AUC0-∞ is determined for the period up to 72 hours post-single dose. AUC0-∞ is an estimate of total plasma exposure from dosing to (extrapolated) infinity. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*µM | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
Up to 14 days
All treated participants are included.
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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 | Moderate Hepatic Impairment (Panel A) | Participants with moderate HI (eGFR of ≤60mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | 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 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 6, 2017 | Oct 22, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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Apparent t1/2 is the elimination half-life of MK-3866 from plasma. |
| Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Clearance (CL) of MK-3866 | CL is the volume of plasma from which the study drug is completely removed per unit time. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Volume of Distribution (Vz) of MK-3866 | Vz is the apparent volume of distribution during the terminal phase. | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
| Renal Clearance (CLr) of MK-3866 | CLr is the volume of plasma from which the study drug is completely removed per unit time by the kidney (i.e., excreted into the urine). Urine samples are collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available. | Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose |
| Number of Participants With at Least One Adverse Event (AE) | An AE is 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 this treatment. | Up to 14 days |
| Number of Participants Who Discontinued the Study Due to an AE | An AE is 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 this treatment. | Up to 14 days |
| Orlando |
| Florida |
| 32809 |
| United States |
Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. |
|
|
| Primary | Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last) | AUC0-last is determined for the period up to 72 hours post-single dose. AUC0-last is an estimate of total plasma exposure from dosing to the time of last measurable sample. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*µM | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
|
|
| Primary | Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr) | AUC0-24 is determined for the period up to 24 hours post-single dose. AUC0-24 is an estimate of total daily plasma exposure from dosing to 24 hours postdose. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*µM | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose |
|
|
|
| Primary | Concentration at the End of Infusion (Ceoi) of MK-3866 | The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | µM | 0.5 (end of infusion) hours postdose |
|
|
|
| Primary | Time to Maximum Concentration (Tmax) of MK-3866 | Tmax is the time at which the maximum plasma drug concentration is detected. | All treated participants with data available are included. | Posted | Median | Full Range | hours | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
|
|
| Primary | Apparent Terminal Half-life (t1/2) of MK-3866 | Apparent t1/2 is the elimination half-life of MK-3866 from plasma. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
|
|
| Primary | Clearance (CL) of MK-3866 | CL is the volume of plasma from which the study drug is completely removed per unit time. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters/hour | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
|
|
| Primary | Volume of Distribution (Vz) of MK-3866 | Vz is the apparent volume of distribution during the terminal phase. | All treated participants with data available are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose |
|
|
|
| Secondary | Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe) | Fe is the amount of drug excreted unchanged in urine. Urine samples were collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available. | Urine samples were collected but were not analyzed. | Posted | Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose |
|
|
| Secondary | Renal Clearance (CLr) of MK-3866 | CLr is the volume of plasma from which the study drug is completely removed per unit time by the kidney (i.e., excreted into the urine). Urine samples are collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available. | Urine samples were collected but were not analyzed. | Posted | Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose |
|
|
| Secondary | Number of Participants With at Least One Adverse Event (AE) | An AE is 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 this treatment. | All treated participants are included. | Posted | Number | Participants | Up to 14 days |
|
|
|
| Secondary | Number of Participants Who Discontinued the Study Due to an AE | An AE is 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 this treatment. | All treated participants are included. | Posted | Number | Participants | Up to 14 days |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Severe Hepatic Impairment (Panel B) | Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1. | 0 | 4 | 0 | 4 | 1 | 4 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.