A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005)
Condition: Infectious Disease
MeSH terms: Communicable Diseases; Infections; Renal Insufficiency
Intervention: MK-7655; Imipenem + Cilastatin; Caffeine; Midazolam; Omeprazole
Intervention description: 125 mg intravenous (IV) over 30 minutes as a single dose; 250 mg IV over 30 minutes as a single dose; Caffeine caplet, single 200 mg dose, orally; Midazolam hcl syrup single 2.0 mg dose by mouth.; Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
Intervention MeSH terms: Imipenem; Relebactam; Cilastatin, Imipenem Drug Combination; Midazolam; Caffeine; Omeprazole; Cilastatin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a 2-part study of the pharmacokinetics (PK) of MK-7655. In Part I, the PK of a single
      125 mg dose of MK-7655 given in combination with 250 mg of PRIMAXIN® (imipenem + cilastatin)
      will be determined in participants with impaired renal function and matched control
      participants. In Part II, the potential for renal insufficiency to affect non-renal clearance
      mechanisms will be investigated.
    

Eligibility criteria:

        Inclusion criteria

          -  Participants of reproductive potential (male or female) must be willing to use
             contraception.

          -  Body Mass Index (BMI) ≤40 kg/m^2

          -  Weight >60 kg at screening visit

          -  No clinically significant abnormality on electrocardiogram (ECG) at screening visit
             and/or prior to administration of the initial dose of study drug

          -  Panels A-D: smokers will be limited to no more that 10 cigarettes per day.

          -  Panels E-H: nonsmoker or has not used nicotine for at least 6 months

          -  In good health (stable health for participants with renal impairment)

        Exclusion criteria

          -  Pregnant or breastfeeding.

          -  History of recent stroke, chronic seizures, or major neurological disorder

          -  History of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, immunological, respiratory, or genitourinary abnormalities or diseases

          -  History of malignant neoplastic disease. Exceptions: (1) adequately treated
             non-melanomatous skin carcinoma or carcinoma in situ of the cervix; (2) other
             malignancies that have been successfully treated ≥10 years prior to the screening
             visit

          -  Panels A-D: Use of any medication (prescription or non-prescription) or herbal
             remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2
             weeks (or 5 half-lives) prior to administration of the initial dose of study drug to
             the post study visit

          -  Panels E-H: Use of any medication (prescription or non-prescription) or herbal
             remedies (such as St. John's Wort [Hypericum perforatum]) that are inhibitors or
             inducers of CYP1A2, CYP2C19, CYP34A, or substrates of CYP2C19, beginning approximately
             2 weeks (or 5 half-lives) prior to administration of the probe cocktail, until the
             post-study visit

          -  Consumption of greater than 3 glasses of alcoholic beverages (1 glass is approximately
             equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits
             [25 mL/1 ounce]) per day

          -  Consumption of greater than 6 servings (1 serving is approximately equivalent to 120
             mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day

          -  Major surgery, donation or loss of 1 unit of blood (approximately 500 mL), or
             participation in another investigational study within 4 weeks prior to the screening
             visit

          -  History of multiple and/or severe allergies (including latex allergy), or prior
             anaphylactic reaction or intolerability to prescription or non-prescription drugs or
             food

          -  History of hypersensitivity to PRIMAXIN® IV or other beta lactam antibiotic (including
             but not limited to penicillins, cephalosporins, monobactams and carbapenems)

          -  Regular user (including recreational use of drugs [including alcohol]) within
             approximately 12 months of screening visit

          -  History of kidney removal and/or renal transplant

          -  History of Clostridium difficile colitis or known C. difficile colonization