Clinical trial NCT03295266: Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)
Official title: An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatic Insufficiency
Antibacterial Agents
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-09-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)
timeFrame: 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
measure: Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last)
timeFrame: 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
measure: Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)
timeFrame: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose
measure: Concentration at the End of Infusion (Ceoi) of MK-3866
timeFrame: 0.5 (end of infusion) hours postdose
measure: Time to Maximum Concentration (Tmax) of MK-3866
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2) of MK-3866
timeFrame: 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
measure: Clearance (CL) of MK-3866
timeFrame: 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
measure: Volume of Distribution (Vz) of MK-3866
timeFrame: 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 outcomes:
measure: Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)
timeFrame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
measure: Renal Clearance (CLr) of MK-3866
timeFrame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: Up to 14 days
measure: Number of Participants Who Discontinued the Study Due to an AE
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami ( Site 0001)
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0002)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: