A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Infectious Disease

Treatments: Drug: Caffeine; Drug: Imipenem + Cilastatin; Drug: Omeprazole; Drug: MK-7655; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT01275170

7655-005

Details and patient eligibility

About

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.

Enrollment: 49 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 8 patient groups

Panel A Mild Renal Impairment

Experimental group

Description:

Participants with an eGFR of \>50 to \<80 mL/min/1.73 m\^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.

Treatment:

Drug: MK-7655

Drug: Imipenem + Cilastatin

Panel B Healthy Participants

Experimental group

Description:

A subset of healthy control participants were matched specifically to participants in Panel A and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.

Treatment:

Drug: MK-7655

Drug: Imipenem + Cilastatin

Panel C Moderate Renal Impairment

Experimental group

Description:

Participants with an eGFR of 30 to 50 mL/min/1.73 m\^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.

Treatment:

Drug: MK-7655

Drug: Imipenem + Cilastatin

Panel D Healthy Participants

Experimental group

Description:

A subset of healthy control participants were matched specifically to participants in Panel C and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.

Treatment:

Drug: MK-7655

Drug: Imipenem + Cilastatin

Panel E Severe Renal Impairment

Experimental group

Description:

Participants with an eGFR \<30 mL/min/1.73 m\^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.

Treatment:

Drug: Midazolam

Drug: MK-7655

Drug: Omeprazole

Drug: Imipenem + Cilastatin

Drug: Caffeine

Panel F Healthy Participants

Experimental group

Description:

A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.

Treatment:

Drug: Midazolam

Drug: MK-7655

Drug: Omeprazole

Drug: Imipenem + Cilastatin

Drug: Caffeine

Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)

Experimental group

Description:

Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).

Treatment:

Drug: Midazolam

Drug: MK-7655

Drug: Omeprazole

Drug: Imipenem + Cilastatin

Drug: Caffeine

Panel H Healthy Volunteers

Experimental group

Description:

A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.

Treatment:

Drug: Midazolam

Drug: MK-7655

Drug: Omeprazole

Drug: Imipenem + Cilastatin

Drug: Caffeine