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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-7655

The percentage of MK-7655 that is removed by hemodialysis

Secondary outcome:

Plasma concentration at the end of the infusion (C[EOI]) of MK-7655

Time 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

Page last updated: August 23, 2015

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