Infectious DiseasePhase 1NCT01275170

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

A Phase 1 study testing MK-7655, Imipenem + Cilastatin and Caffeine in people with Infectious Disease, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Infectious Disease
What is being tested?: MK-7655, Imipenem + Cilastatin and Caffeine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 49 participants
Where: No sites listed yet
Study dates: 28 Jan 2011to 5 Mar 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

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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

About this study

Official title: A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function

Conditions: Infectious Disease
Being tested: MK-7655, Imipenem + Cilastatin, Caffeine, Midazolam, Omeprazole
Medical subject headings: Communicable Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-7655Drug
Also called RELEBACTAM®
125 mg intravenous (IV) over 30 minutes as a single dose
Imipenem + CilastatinDrug
Also called PRIMAXIN®
250 mg IV over 30 minutes as a single dose
CaffeineDrug
Also called No Doz®
Caffeine caplet, single 200 mg dose, orally
MidazolamDrug
Also called VERSED®
Midazolam hcl syrup single 2.0 mg dose by mouth.
OmeprazoleDrug
Also called PRILOSEC®
Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally

Study groups in NCT01275170
Study group	Role	What they receive
Panel A Mild Renal Impairment	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin
Panel B Healthy Participants	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin
Panel C Moderate Renal Impairment	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin
Panel D Healthy Participants	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin
Panel E Severe Renal Impairment	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin; Drug: Caffeine; Drug: Midazolam; Drug: Omeprazole
Panel F Healthy Participants	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin; Drug: Caffeine; Drug: Midazolam; Drug: Omeprazole
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)	Experimental	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). Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin; Drug: Caffeine; Drug: Midazolam; Drug: Omeprazole
Panel H Healthy Volunteers	Experimental	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. Receives: Drug: MK-7655; Drug: Imipenem + Cilastatin; Drug: Caffeine; Drug: Midazolam; Drug: Omeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)*QB*[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)] where QB=350 mL/min and Hct=hematocrit.
Measured: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS[100*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration].
Measured: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

Secondary outcomes (24)

Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®
Ceoi is the observed plasma drug concentration at the end of IV infusion.
Measured: At 0.5 hours postdose
Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®
CLpred is the predicted apparent total body clearance of drug.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®
VZpred is the predicted volume of distribution during the terminal phase.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®
Tmax is the time at which the highest plasma drug concentration was observed.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®
Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: AUC0-inf of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Ceoi of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
Measured: At 0.5 hours postdose
Part 1: CLpred of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: VZpred of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Tmax of Imipenem in Combination With MK-7655
Tmax is the time at which the highest plasma drug concentration was observed.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent t½ of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: AUC0-inf of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Ceoi of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
Measured: At 0.5 hours postdose
Part 1: CLpred of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: VZpred of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Tmax of Cilastin in Combination With MK-7655
Tmax is the time at which the highest plasma drug concentration was observed.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent t½ of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
Measured: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Renal Clearance (CLR) of MK-7655 in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Measured: Predose to 24 hours postdose
Part 1: CLR of Imipenem in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Measured: Predose to 24 hours postdose
Part 1: CLR of Cilastin in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Measured: Predose to 24 hours postdose
Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2
Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Measured: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4
Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Measured: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19
Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Measured: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jan 20115 Mar 2012

First posted12 Jan 2011 (estimated)
Study start28 Jan 2011
Primary completion5 Mar 2012
Study completion5 Mar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infectious DiseaseStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01275170
Sponsor's protocol ID: 7655-005
Status last verified: May 2020
First submitted: 10 Jan 2011
Last updated: 11 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Bhagunde P, Colon-Gonzalez F, Liu Y, Wu J, Xu SS, Garrett G, Jumes P, Lasseter K, Marbury T, Rizk ML, Lala M, Rhee EG, Butterton JR, Boundy K. Impact of renal impairment and human organic anion transporter inhibition on pharmacokinetics, safety and tolerability of relebactam combined with imipenem and cilastatin. Br J Clin Pharmacol. 2020 May;86(5):944-957. doi: 10.1111/bcp.14204. Epub 2020 Jan 23.
PubMed 31856304

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function
ClinicalTrials.gov ID: NCT01275170
Acronym / sponsor ID: 7655-005
Conditions: Infectious Disease
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 28 Jan 2011 (actual)
Primary completion: 5 Mar 2012 (actual)
Study completion: 5 Mar 2012 (actual)
First posted: 12 Jan 2011 (estimated)
Results: Posted 19 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Panel A Mild Renal Impairment	Experimental	Drug: MK-7655, Drug: Imipenem + CilastatinParticipants 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.
Panel B Healthy Participants	Experimental	Drug: MK-7655, Drug: Imipenem + CilastatinA 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.
Panel C Moderate Renal Impairment	Experimental	Drug: MK-7655, Drug: Imipenem + CilastatinParticipants 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.
Panel D Healthy Participants	Experimental	Drug: MK-7655, Drug: Imipenem + CilastatinA 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.
Panel E Severe Renal Impairment	Experimental	Drug: MK-7655, Drug: Imipenem + Cilastatin, Drug: Caffeine, Drug: Midazolam, Drug: OmeprazoleParticipants 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.
Panel F Healthy Participants	Experimental	Drug: MK-7655, Drug: Imipenem + Cilastatin, Drug: Caffeine, Drug: Midazolam, Drug: OmeprazoleA 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.
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)	Experimental	Drug: MK-7655, Drug: Imipenem + Cilastatin, Drug: Caffeine, Drug: Midazolam, Drug: OmeprazoleParticipants 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).
Panel H Healthy Volunteers	Experimental	Drug: MK-7655, Drug: Imipenem + Cilastatin, Drug: Caffeine, Drug: Midazolam, Drug: OmeprazoleA 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-7655Also: RELEBACTAM®125 mg intravenous (IV) over 30 minutes as a single dose	Drug	Panel A Mild Renal Impairment, Panel B Healthy Participants, Panel C Moderate Renal Impairment, Panel D Healthy Participants, Panel E Severe Renal Impairment, Panel F Healthy Participants, Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD), Panel H Healthy Volunteers
Imipenem + CilastatinAlso: PRIMAXIN®250 mg IV over 30 minutes as a single dose	Drug	Panel A Mild Renal Impairment, Panel B Healthy Participants, Panel C Moderate Renal Impairment, Panel D Healthy Participants, Panel E Severe Renal Impairment, Panel F Healthy Participants, Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD), Panel H Healthy Volunteers
CaffeineAlso: No Doz®Caffeine caplet, single 200 mg dose, orally	Drug	Panel E Severe Renal Impairment, Panel F Healthy Participants, Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD), Panel H Healthy Volunteers
MidazolamAlso: VERSED®Midazolam hcl syrup single 2.0 mg dose by mouth.	Drug	Panel E Severe Renal Impairment, Panel F Healthy Participants, Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD), Panel H Healthy Volunteers
OmeprazoleAlso: PRILOSEC®Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally	Drug	Panel E Severe Renal Impairment, Panel F Healthy Participants, Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD), Panel H Healthy Volunteers

Primary outcome

Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)*QB*[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)] where QB=350 mL/min and Hct=hematocrit.
Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS[100*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration].

24 secondary outcomes

Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®
Time frame: At 0.5 hours postdose
Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: AUC0-inf of Imipenem in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Ceoi of Imipenem in Combination With MK-7655
Time frame: At 0.5 hours postdose
Part 1: CLpred of Imipenem in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: VZpred of Imipenem in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Tmax of Imipenem in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent t½ of Imipenem in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: AUC0-inf of Cilastin in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Ceoi of Cilastin in Combination With MK-7655
Time frame: At 0.5 hours postdose
Part 1: CLpred of Cilastin in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: VZpred of Cilastin in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Tmax of Cilastin in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Apparent t½ of Cilastin in Combination With MK-7655
Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
Part 1: Renal Clearance (CLR) of MK-7655 in Urine
Time frame: Predose to 24 hours postdose
Part 1: CLR of Imipenem in Urine
Time frame: Predose to 24 hours postdose
Part 1: CLR of Cilastin in Urine
Time frame: Predose to 24 hours postdose
Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)
Time frame: Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)

Results and safety

Results posted to the registry on 19 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Panel A: Mild Renal Impairment	7	6
Panel B: Healthy Controls to Panel A	6	6
Panel C: Moderate Renal Impairment	6	6
Panel D: Healthy Controls to Panel C	6	6
Panel E: Severe Renal Impairment	6	6
Panel F: Healthy Controls to Panel E	6	6
Panel G: ESRD/HD Participants	6	6
Panel H: Healthy Controls to Panel G	6	6

Primary outcome: Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®

Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose. Geometric mean (95% Confidence Interval). Unit: µM*hr

Measure	Panel A: Mild Renal Impairment n = 6	Panel B: Healthy Controls to Panel A n = 6	Panel C: Moderate Renal Impairment n = 6	Panel D: Healthy Controls to Panel C n = 6	Panel E: Severe Renal Impairment n = 6	Panel F: Healthy Controls to Panel E n = 6	Panel G: ESRD/HD Period 1 Postdialysis n = 6	Panel H: Healthy Controls to Panel G n = 6	Panel G: ESRD/HD Period 2 Predialysis n = 6
Value	73.5 (50.0 to 108)	45.0 (32.4 to 62.6)	115 (79.8 to 165)	52.3 (37.7 to 72.7)	236 (171 to 325)	48.5 (35.3 to 66.4)	414 (280 to 612)	44.5 (29.1 to 67.9)	78.0 (50.3 to 121)

Panel A: Mild Renal Impairment vs Panel B: Healthy Controls to Panel A: GMR: 1.63 (90% CI 1.12 to 2.39)
Panel C: Moderate Renal Impairment vs Panel D: Healthy Controls to Panel C: GMR: 2.19 (90% CI 1.51 to 3.18)
Panel E: Severe Renal Impairment vs Panel F: Healthy Controls to Panel E: GMR: 4.87 (90% CI 3.37 to 7.04)

Population analysed: Treated participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included. Per protocol, data for Panel G were reported separately for post-dialysis and pre-dialysis.

Primary outcome: Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)

Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose. Geometric mean (Geometric Coefficient of Variation). Unit: mL/min

Measure	Panel G: ESRD/HD Period 2 Predialysis n = 6
1 hour postdose	172 (3.5)
1.5 hours postdose	158 (9.4)
2 hours postdose	170 (5.9)
2.5 hours postdose	166 (7.0)
3.0 hours postdose	171 (5.4)
3.5 hours postdose	177 (15.7)
4 hours postdose	204 (20.2)
4.5 hours postdose	198 (23.0)

Population analysed: Treated participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included. Per protocol, only Panel G participants requiring HD were included in the analysis.

Primary outcome: Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)

Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose. Geometric mean (Geometric Coefficient of Variation). Unit: Extraction coefficient

Measure	Panel G: ESRD/HD Period 2 Predialysis n = 6
1 hour postdose	73 (1.8)
1.5 hours postdose	67 (9.5)
2 hours postdose	73 (4.5)
2.5 hours postdose	71 (5.6)
3.0 hours postdose	73 (4.1)
3.5 hours postdose	76 (15.7)
4 hours postdose	87 (19.6)
4.5 hours postdose	84 (22.2)

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Panel A: Mild Renal Impairment	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7
Panel C: Moderate Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Panel E: Severe Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Panel G: ESRD/HD Participants	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Healthy Matched Controls	0 of 24 (0%)	0 of 24 (0%)	0 of 24
Panel E: Severe Renal Impairment (Part 2)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Panel G: ESRD/HC (Part 2)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Healthy Matched Controls (Part 2)	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31856304Bhagunde P, Colon-Gonzalez F, Liu Y, Wu J, Xu SS, Garrett G, Jumes P, Lasseter K, Marbury T, Rizk ML, Lala M, Rhee EG, Butterton JR, Boundy K. Impact of renal impairment and human organic anion transporter inhibition on pharmacokinetics, safety and tolerability of relebactam combined with imipenem and cilastatin. Br J Clin Pharmacol. 2020 May;86(5):944-957. doi: 10.1111/bcp.14204. Epub 2020 Jan 23.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-7655, Imipenem + Cilastatin and Caffeine in people with Infectious Disease, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® (time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01275170, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.