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:
Merck
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT01275170
First received: January 10, 2011
Last updated: March 21, 2012
Last verified: March 2012
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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:
Drug Information available for:
Midazolam hydrochloride
Omeprazole
Imipenem
Cilastatin sodium
Omeprazole magnesium
Esomeprazole
Esomeprazole Sodium
Esomeprazole magnesium
U.S. FDA Resources
Further study details as provided by Merck:
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
No Contacts or Locations Provided
More Information
No publications provided
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 18, 2012
No publications provided
Responsible Party: | Merck |
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 Cilastatin Omeprazole Imipenem Central Nervous System Stimulants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses |
Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Protease Inhibitors Adjuvants, Anesthesia Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Hypnotics and Sedatives Anesthetics, Intravenous |
ClinicalTrials.gov processed this record on October 18, 2012