Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin in Participants With Renal Insufficiency in the Presence and Absence of Rifampin (MK-0000-386)
Condition: Renal Insufficiency
MeSH terms: Renal Insufficiency
Intervention: Midazolam oral solution; Dabigatran and pitavastatin oral solution; Atorvastatin and rosuvastatin oral solution; Rifampin
Intervention description: Midazolam hydrochloride 10 μg (1 mL of 10 μg/mL oral solution), administered orally as part of a microdose cocktail; 375/10 μg dabigatran etexilate and pitavastatin (1 mL of 375/10 μg/mL oral solution), administered orally as part of a microdose cocktail; 100/50 μg atorvastatin and rosuvastatin (2 mL of 50/25 μg/mL oral solution), administered orally as part of a microdose cocktail; Rifampin 600 mg single dose (two 300 mg capsules) administered orally
Intervention MeSH terms: Rifampin; Midazolam; Dabigatran; Atorvastatin; Rosuvastatin Calcium; Pitavastatin; Pharmaceutical Solutions
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 78 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this open-label, 2-period, fixed-sequence study is to characterize the plasma
      pharmacokinetic profiles of midazolam, dabigatran, pitavastatin, atorvastatin, and
      rosuvastatin following a single oral dose administration of a microdose cocktail in healthy
      participants, in participants with mild, moderate, severe (not on dialysis) renal impairment,
      and in participants with end-stage renal disease (ESRD; on dialysis).
    

Eligibility criteria:

        Inclusion Criteria:

        All participants (with mild, moderate or severe renal impairment, end stage renal disease,
        or healthy):

          -  a female must be non-pregnant, non-breast feeding and if she is of reproductive
             potential: must agree to use (and/or have their partner use) two acceptable methods of
             birth control beginning at screening, throughout the study and until 2 weeks after the
             last dosing of study drug

          -  a female of non-childbearing potential: must have undergone a sterilization procedure
             at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at
             least 1 year prior to the first dose

          -  a non-vasectomized male participant must agree to use a condom with spermicide or
             abstain from sexual intercourse from the first dose until 90 days after the last dose
             of study drug

          -  a male participant must agree not to donate sperm from dosing until 90 days after the
             last dose of study drug

          -  has a body mass index (BMI) ≤ 40.0 kg/m^2

          -  is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent)

        Participants with mild, moderate or severe renal impairment or end stage renal disease:

          -  has a clinical diagnosis of renal impairment and meets the protocol-specified renal
             impairment function qualifications at the prestudy visit (screening)

        Healthy participants:

          -  has baseline creatinine clearance ≥ 90 mL/min based on Cockcroft-Gault equation

          -  is judged to be in good health based on medical history, physical examination, vital
             signs, pulse oximetry, and laboratory safety tests

        Exclusion Criteria:

        All participants (with mild, moderate or severe renal impairment, end stage renal disease,
        or healthy):

          -  is mentally or legally incapacitated or has significant emotional problems at the time
             of the screening visit or expected during the conduct of the study.

          -  history or presence of clinically significant medical or psychiatric condition or
             disease

          -  history of stroke, chronic seizures, or major neurological disorders

          -  history of malignant neoplastic disease

          -  history or presence of alcoholism or drug abuse within the past 6 months

          -  female participant who is pregnant or lactating

        Participants with mild, moderate or severe renal impairment:

          -  has had a renal transplant or has had nephrectomy

          -  has uncontrolled type 2 diabetes mellitus (T2DM), a history of Type 1 diabetes, or
             ketoacidosis

          -  history of significant endocrine, gastrointestinal, cardiovascular, hematological,
             immunological, respiratory, or genitourinary diseases

        Participants with end stage renal disease (ESRD):

          -  had a failed renal allograft within the last 2 years prior to the first dose, or a
             successful renal allograft

          -  has uncontrolled T2DM, a history of Type 1 diabetes, or ketoacidosis

          -  history of significant endocrine, gastrointestinal, cardiovascular, hematological,
             immunological, respiratory, or genitourinary diseases

        Healthy participants:

          -  history of hypoglycemia, glucose intolerance, T2DM, or ketoacidosis

          -  history of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic, immunological, renal, respiratory, or genitourinary
             abnormalities or diseases.