A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005 AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01275170
First received: January 10, 2011
Last updated: March 21, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Infectious Disease
Drug: MK-7655
Drug: imipenem + cilastatin
Drug: caffeine
Drug: midazolam
Drug: omeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • The area under the curve of plasma concentration of drug against time (AUC) [0-infinity]after administration of MK-7655 [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • The percentage of MK-7655 that is removed by hemodialysis [ Time Frame: Immediately prior to infusion on Day 1, and immediately after infusion on Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma concentration at the end of the infusion (C[EOI]) of MK-7655 [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Time at which maximum concentration occurs (Tmax) for MK-7655 [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Apparent terminal half-life of MK-7655 [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Renal clearance of MK-7655 [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Fraction of MK-7655 dose excreted unchanged in urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From Hour 0 to Hour 24 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From Hour 0 to Hour 24 ] [ Designated as safety issue: No ]
  • Plasma AUC[0-infinity] of imipenem [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Plasma C[EOI] of imipenem [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Plasma Tmax of imipenem [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Apparent terminal half-life of imipenem [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Renal clearance of imipenem [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Fraction of imipenem dose excreted unchanged in urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Plasma AUC[0-infinity] of cilastatin [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Plasma C[EOI] of cilastatin [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Plasma Tmax of cilastatin [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Apparent terminal half-life of cilastatin [ Time Frame: 14 hours ] [ Designated as safety issue: No ]
  • Renal clearance of cilastatin [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Fraction of cilastatin dose excreted unchanged in urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Number of participants with clinical and laboratory adverse events (AEs) [ Time Frame: Prior to first dose through 14 days after last dose. ] [ Designated as safety issue: Yes ]

Enrollment: 49
Study Start Date: January 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A Mild Renal Impairment
Participants in this arm will not participate in Part II of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Experimental: Panel B Healthy Participants
Participants in this arm will not participate in Part II of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Experimental: Panel C Moderate Renal Impairment
Participants in this arm will not participate in Part II of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Experimental: Panel D Healthy Participants
Participants in this arm will not participate in Part II of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Experimental: Panel E Severe Renal Impairment
Panel E participants will receive the probe cocktail (caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg) at Hour 0 in Part 2 of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Drug: caffeine
caffeine caplet, single 200 mg dose, orally
Other Name: No Doz®
Drug: midazolam
midazolam hcl syrup, single 2.0 mg dose, orally
Drug: omeprazole
omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
Experimental: Panel F Healthy Participants
Panel F participants will receive the probe cocktail (caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg) at Hour 0 in Part 2 of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Drug: caffeine
caffeine caplet, single 200 mg dose, orally
Other Name: No Doz®
Drug: midazolam
midazolam hcl syrup, single 2.0 mg dose, orally
Drug: omeprazole
omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
Experimental: Panel G End Stage Renal Disease with Dialysis
Panel G participants will receive the probe cocktail (caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg) at Hour 0 in Part 2 of the study, during both Period 1 and Period 2.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Drug: caffeine
caffeine caplet, single 200 mg dose, orally
Other Name: No Doz®
Drug: midazolam
midazolam hcl syrup, single 2.0 mg dose, orally
Drug: omeprazole
omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
Experimental: Panel H Healthy Volunteers
Panel H participants will receive the probe cocktail (caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg) at Hour 0 in Part 2 of the study.
Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Drug: imipenem + cilastatin
250 mg IV over 30 minutes as a single dose
Other Name: PRIMAXIN®
Drug: caffeine
caffeine caplet, single 200 mg dose, orally
Other Name: No Doz®
Drug: midazolam
midazolam hcl syrup, single 2.0 mg dose, orally
Drug: omeprazole
omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01275170     History of Changes
Other Study ID Numbers: MK-7655-005
Study First Received: January 10, 2011
Last Updated: March 21, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Communicable Diseases
Infection
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Caffeine
Midazolam
Omeprazole
Adjuvants, Anesthesia
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Anti-Ulcer Agents
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Enzyme Inhibitors
GABA Agents
GABA Modulators
Gastrointestinal Agents
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Proton Pump Inhibitors
Psychotropic Drugs
Purinergic Agents

ClinicalTrials.gov processed this record on October 21, 2014