Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin in Participants With Renal Insufficiency in the Presence and Absence of Rifampin (MK-0000-386)

• Status: Completed
• Trial end date: 2018-08-02
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Atorvastatin; Atorvastatin Calcium; Dabigatran; Midazolam; Pharmaceutical Solutions; Pitavastatin; Rifampin; Rosuvastatin Calcium

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.