A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005 AM1)
Information source: Merck Sharp & Dohme Corp.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Infectious Disease
Intervention: MK-7655 (Drug); imipenem + cilastatin (Drug); caffeine (Drug); midazolam (Drug); omeprazole (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Merck Sharp & Dohme Corp.
Summary
Part I of this study will compare the pharmacokinetics of MK-7655, dosed in combination with
PRIMAXIN® (imipenem + cilastatin), in participants with impaired renal function and matched
control participants. In Part II of the study, the potential for renal insufficiency to
affect non-renal clearance mechanisms will be investigated.
Clinical Details
Official title: A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The area under the curve of plasma concentration of drug against time (AUC) [0-infinity]after administration of MK-7655The percentage of MK-7655 that is removed by hemodialysis
Secondary outcome: Plasma concentration at the end of the infusion (C[EOI]) of MK-7655Time at which maximum concentration occurs (Tmax) for MK-7655 Apparent terminal half-life of MK-7655 Renal clearance of MK-7655 Fraction of MK-7655 dose excreted unchanged in urine The plasma AUC[0-infinity] of probe substrates of cytochrome P450 enzymes (CYP) 1A2, 3A4,2 and C19 in participants with severe renal impairment versus healthy matched subjects The plasma AUC[0-infinity] of probe substrates of cytochrome P450 enzymes (CYP) 1A2, 3A4,2 and C19 in participants with end stage renal disease (ESRD), before and after hemodialysis, versus healthy matched subjects Plasma AUC[0-infinity] of imipenem Plasma C[EOI] of imipenem Plasma Tmax of imipenem Apparent terminal half-life of imipenem Renal clearance of imipenem Fraction of imipenem dose excreted unchanged in urine Plasma AUC[0-infinity] of cilastatin Plasma C[EOI] of cilastatin Plasma Tmax of cilastatin Apparent terminal half-life of cilastatin Renal clearance of cilastatin Fraction of cilastatin dose excreted unchanged in urine Number of participants with clinical and laboratory adverse events (AEs)
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
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
Locations and Contacts
Additional Information
Starting date: January 2011
Last updated: November 13, 2014
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