- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03295266
Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)
October 22, 2019 updated by: Merck Sharp & Dohme LLC
An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Hialeah, Florida, United States, 33014
- Clinical Pharmacology of Miami ( Site 0001)
-
Orlando, Florida, United States, 32809
- Orlando Clinical Research Center ( Site 0002)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Body mass index ≥19 & ≤40 kg/m^2
- Continuous non-smoker prior to screening & enrollment
- HI Participants: Baseline health judged to be stable based on medical history (except for the HI condition), physical examination, vital signs, electrocardiograms, & laboratory safety tests
- Healthy control participants: Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms
- HI Participants: Diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis
- HI Participants - Panel A (moderate HI) only: score on the Child-Pugh scale from 7 to 9 (moderate HI). At least 3 participants must have a score of 2 or higher on at least one of the laboratory parameters (i.e., albumin, international normalized ratio, and/or bilirubin) on the Child-Pugh scale
- HI Participants - Panel B (severe HI) only: Score on the Child-Pugh scale from 10 to 15 (severe HI)
- Is completely informed of the unknown risks of pregnancy & agrees not to become pregnant or father a child during time in study
- For a female of childbearing potential: is either sexually inactive (abstinent) for 14 days prior to dosing & throughout the study or is using an acceptable birth control method
- Non-vasectomized male: Participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing
Exclusion Criteria:
- Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- Has a history or presence of clinically significant medical or psychiatric condition or disease (other than HI - Panels A & B) that might confound the results of the study or poses an additional risk to the participant. Remote history of cholecystectomy that is not an active issue may be included.
- Panels A & B: Has a clinically significant history of cancer. Remote history with full cure or limited disease with complete resection (cure) may be included
- Has a history of drug/alcohol abuse within the past 6 months prior to dosing (Panels A & B) or within the past 2 years prior to dosing (Panel C [Healthy controls])
- Panels A & B: Consumes more than 3 glasses of alcoholic beverages (1 glass approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day, within 6 months of screening. Participants that consume 4 glasses of alcoholic beverages/day may be enrolled
- Panels A & B: Consumes excessive amounts, defined as more than 6 servings (1 serving approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy-drinks, or other caffeinated beverages/day
- Panels A & B: Has a history of a liver transplant
- Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
- Has moderate or severe renal insufficiency (estimated glomerular filtration rate of ≤60 mL/min/1.73 m2 for moderate HI or healthy control participants or ≤50 mL/min/1.73 m2 for severe HI participants)
- Panel C: Has positive macroscopic urine protein at screening (trace protein by dipstick allowed)
- Is a female participant who is pregnant or lactating
- Has positive results for the urine or breath alcohol screen and/or urine drug screen at screening
- Has positive results at screening for human immunodeficiency virus (HIV) (Panels A & B) or for HIV, HBsAg, or hepatitis C virus (HCV) (Panel C)
- Panels A & B: Participants with active HCV infection or hepatitis B virus (HBV) infection. Participants with prior/inactive HCV infection or past HBV infection may be enrolled.
- Is unable to refrain from or anticipates use of any medication or substance prohibited in study
- Has taken amiodarone at any time in their life
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Moderate Hepatic Impairment (Panel A)
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.
|
Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
|
Experimental: Severe Hepatic Impairment (Panel B)
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.
|
Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
|
Experimental: Healthy Matched Controls (Panel C)
Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1.
|
Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)
Time Frame: 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
|
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)
Time Frame: 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
|
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)
Time Frame: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose
|
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
Time Frame: 0.5 (end of infusion) hours postdose
|
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
Time Frame: 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
|
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
Time Frame: 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 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
Time Frame: 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
|
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
Time Frame: 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
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)
Time Frame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
|
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
|
Renal Clearance (CLr) of MK-3866
Time Frame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
|
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)
Time Frame: Up to 14 days
|
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
Time Frame: Up to 14 days
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 19, 2017
Primary Completion (Actual)
March 15, 2018
Study Completion (Actual)
March 15, 2018
Study Registration Dates
First Submitted
September 25, 2017
First Submitted That Met QC Criteria
September 25, 2017
First Posted (Actual)
September 27, 2017
Study Record Updates
Last Update Posted (Actual)
November 13, 2019
Last Update Submitted That Met QC Criteria
October 22, 2019
Last Verified
October 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3866-006
- MK-3866-006 (Other Identifier: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hepatic Insufficiency
-
PfizerCompletedHealthy, Hepatic InsufficiencyUnited States
-
BeiGeneCompletedHepatic Insufficiency & Healthy SubjectsUnited States
-
BayerCompletedHepatic Insufficiency, Renal InsufficiencyGermany, Romania
-
Cardiox CorporationTerminatedHepatic Failure
-
Novartis PharmaceuticalsCompletedHepatic FailureUnited States
-
Centre Hospitalier Universitaire de NiceCompleted
-
Biotie Therapies Inc.Acorda TherapeuticsTerminatedHepatic ImpairmentUnited States
-
PfizerMedivation, Inc.Completed
-
Assistance Publique - Hôpitaux de ParisUnknownFulminating Hepatic FailureFrance
-
National Taiwan University HospitalUnknownLiver Failure | Critical CareTaiwan
Clinical Trials on MK-3866
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompletedType 2 Diabetes Mellitus
-
Merck Sharp & Dohme LLCTerminated
-
Merck Sharp & Dohme LLCCompletedHypertension | Isolated Systolic Hypertension (ISH)
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompletedSolid TumorsUnited States, Canada, Switzerland
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompletedHepatitis C Virus Infection