Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)
Condition: Hepatic Insufficiency; Antibacterial Agents
MeSH terms: Hepatic Insufficiency; Liver Failure
Intervention: MK-3866
Intervention description: Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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