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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01275170
Collaborator
(none)
49
Enrollment
8
Arms
13.2
Actual Duration (Months)

Study Details

Study Description

Brief 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. In Part II, the potential for renal insufficiency to affect non-renal clearance mechanisms will be investigated.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function
Actual Study Start Date :
Jan 28, 2011
Actual Primary Completion Date :
Mar 5, 2012
Actual Study Completion Date :
Mar 5, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Panel A Mild Renal Impairment

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.

Drug: MK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    		•
    Experimental: Panel B Healthy Participants

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    		•
    Experimental: Panel C Moderate Renal Impairment

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    		•
    Experimental: Panel D Healthy Participants

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    		•
    Experimental: Panel E Severe Renal Impairment

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    • Drug: Caffeine
    Caffeine caplet, single 200 mg dose, orally
    Other Names:
  • No Doz®

    • Drug: Midazolam
    Midazolam hcl syrup single 2.0 mg dose by mouth.
    Other Names:
  • VERSED®

    • Drug: Omeprazole
    Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
    Other Names:
  • PRILOSEC®

    		•
    Experimental: Panel F Healthy Participants

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    • Drug: Caffeine
    Caffeine caplet, single 200 mg dose, orally
    Other Names:
  • No Doz®

    • Drug: Midazolam
    Midazolam hcl syrup single 2.0 mg dose by mouth.
    Other Names:
  • VERSED®

    • Drug: Omeprazole
    Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
    Other Names:
  • PRILOSEC®

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

    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).

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    • Drug: Caffeine
    Caffeine caplet, single 200 mg dose, orally
    Other Names:
  • No Doz®

    • Drug: Midazolam
    Midazolam hcl syrup single 2.0 mg dose by mouth.
    Other Names:
  • VERSED®

    • Drug: Omeprazole
    Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
    Other Names:
  • PRILOSEC®

    		•
    Experimental: Panel H Healthy Volunteers

    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.

    Drug: MK-7655
    125 mg intravenous (IV) over 30 minutes as a single dose
    Other Names:
  • RELEBACTAM®

    • Drug: Imipenem + Cilastatin
    250 mg IV over 30 minutes as a single dose
    Other Names:
  • PRIMAXIN®

    • Drug: Caffeine
    Caffeine caplet, single 200 mg dose, orally
    Other Names:
  • No Doz®

    • Drug: Midazolam
    Midazolam hcl syrup single 2.0 mg dose by mouth.
    Other Names:
  • VERSED®

    • Drug: Omeprazole
    Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
    Other Names:
  • PRILOSEC®

    		•

    Outcome Measures

    Primary Outcome Measures

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

    2. Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) [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.

    3. Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) [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].

    Secondary Outcome Measures

    1. Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® [At 0.5 hours postdose]

      Ceoi is the observed plasma drug concentration at the end of IV infusion.

    2. Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      CLpred is the predicted apparent total body clearance of drug.

    3. Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      VZpred is the predicted volume of distribution during the terminal phase.

    4. Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Tmax is the time at which the highest plasma drug concentration was observed.

    5. Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.

    6. Part 1: AUC0-inf of Imipenem in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.

    7. Part 1: Ceoi of Imipenem in Combination With MK-7655 [At 0.5 hours postdose]

      Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.

    8. Part 1: CLpred of Imipenem in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.

    9. Part 1: VZpred of Imipenem in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.

    10. Part 1: Tmax of Imipenem in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Tmax is the time at which the highest plasma drug concentration was observed.

    11. Part 1: Apparent t½ of Imipenem in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      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%.

    12. Part 1: AUC0-inf of Cilastin in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.

    13. Part 1: Ceoi of Cilastin in Combination With MK-7655 [At 0.5 hours postdose]

      Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.

    14. Part 1: CLpred of Cilastin in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.

    15. Part 1: VZpred of Cilastin in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.

    16. Part 1: Tmax of Cilastin in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      Tmax is the time at which the highest plasma drug concentration was observed.

    17. Part 1: Apparent t½ of Cilastin in Combination With MK-7655 [Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose]

      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%.

    18. Part 1: Renal Clearance (CLR) of MK-7655 in Urine [Predose to 24 hours postdose]

      CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.

    19. Part 1: CLR of Imipenem in Urine [Predose to 24 hours postdose]

      CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.

    20. Part 1: CLR of Cilastin in Urine [Predose to 24 hours postdose]

      CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.

    21. Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 [Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose]

      Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.

    22. Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 [Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose]

      Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.

    23. Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 [Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose]

      Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.

    24. Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) [Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    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

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT01275170
    Other Study ID Numbers:
    • 7655-005
    First Posted:
    Jan 12, 2011
    Last Update Posted:
    Jun 11, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Communicable Diseases
    Infections
    Renal Insufficiency
    Imipenem
    Relebactam
    Cilastatin, Imipenem Drug Combination
    Midazolam
    Caffeine
    Omeprazole
    Cilastatin

    Study Results

    Participant Flow

    Recruitment Details Participants with varying degrees of renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis (HD) [based on estimated glomerular filtration rate (eGFR)], or healthy matched controls were enrolled at 2 study sites in the United States.
    Pre-assignment Detail All panels participated in Part 1 of the study. Panels E to H also participated in Part 2 of the study.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Participants Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² 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. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Period Title: Part 1: Period 1
    STARTED 7 6 6 6 6 6 6 6
    Treated 6 6 6 6 6 6 6 6
    COMPLETED 6 6 6 6 6 6 6 6
    NOT COMPLETED 1 0 0 0 0 0 0 0
    Period Title: Part 1: Period 1
    STARTED 0 0 0 0 0 0 6 6
    COMPLETED 0 0 0 0 0 0 6 6
    NOT COMPLETED 0 0 0 0 0 0 0 0
    Period Title: Part 1: Period 1
    STARTED 0 0 0 0 6 6 6 6
    COMPLETED 0 0 0 0 6 6 6 6
    NOT COMPLETED 0 0 0 0 0 0 0 0
    Period Title: Part 1: Period 1
    STARTED 0 0 0 0 0 0 6 6
    COMPLETED 0 0 0 0 0 0 6 6
    NOT COMPLETED 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Participants Panel H: Healthy Controls to Panel G Total
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² 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. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Total of all reporting groups
    Overall Participants 7 6 6 6 6 6 6 6 49
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    71.1
    (3.4)
    64.5
    (3.9)
    68.3
    (5.0)
    64.2
    (5.7)
    62.8
    (7.5)
    60.5
    (6.4)
    44.5
    (7.9)
    41.5
    (11.5)
    59.9
    (12.1)
    Sex: Female, Male (Count of Participants)
    Female
    3
    42.9%
    2
    33.3%
    3
    50%
    3
    50%
    3
    50%
    3
    50%
    2
    33.3%
    2
    33.3%
    21
    42.9%
    Male
    4
    57.1%
    4
    66.7%
    3
    50%
    3
    50%
    3
    50%
    3
    50%
    4
    66.7%
    4
    66.7%
    28
    57.1%

    Outcome Measures

    1. Primary Outcome
    Title Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
    Description AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM*hr]
    73.5
    45.0
    115
    52.3
    236
    48.5
    414
    44.5
    78.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments Geometric mean ratio (GMR) [Renal Impairment/Healthy Control]
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.63
    Confidence Interval (2-Sided) 90%
    1.12 to 2.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.19
    Confidence Interval (2-Sided) 90%
    1.51 to 3.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 4.87
    Confidence Interval (2-Sided) 90%
    3.37 to 7.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 9.32
    Confidence Interval (2-Sided) 90%
    6.45 to 13.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.76
    Confidence Interval (2-Sided) 90%
    1.20 to 2.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®
    Description Ceoi is the observed plasma drug concentration at the end of IV infusion.
    Time Frame At 0.5 hours postdose

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM]
    22.4
    20.4
    23.5
    22.5
    23.6
    18.1
    53.1
    22.7
    19.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.10
    Confidence Interval (2-Sided) 90%
    0.64 to 1.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.04
    Confidence Interval (2-Sided) 90%
    0.62 to 1.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.30
    Confidence Interval (2-Sided) 90%
    0.77 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.34
    Confidence Interval (2-Sided) 90%
    1.39 to 3.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.85
    Confidence Interval (2-Sided) 90%
    0.50 to 1.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®
    Description CLpred is the predicted apparent total body clearance of drug.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [mL/min]
    81.3
    133
    52.1
    114
    25.3
    123
    14.4
    135
    76.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.61
    Confidence Interval (2-Sided) 90%
    0.42 to 0.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.46
    Confidence Interval (2-Sided) 90%
    0.31 to 0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.21
    Confidence Interval (2-Sided) 90%
    0.14 to 0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.11
    Confidence Interval (2-Sided) 90%
    0.07 to 0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.57
    Confidence Interval (2-Sided) 90%
    0.39 to 0.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®
    Description VZpred is the predicted volume of distribution during the terminal phase.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [liters (L)]
    21.4
    21.6
    22.2
    21.9
    20.1
    22.4
    16.2
    17.0
    55.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.99
    Confidence Interval (2-Sided) 90%
    0.82 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.01
    Confidence Interval (2-Sided) 90%
    0.84 to 1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.90
    Confidence Interval (2-Sided) 90%
    0.74 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.96
    Confidence Interval (2-Sided) 90%
    0.79 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 3.28
    Confidence Interval (2-Sided) 90%
    2.70 to 4.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®
    Description Tmax is the time at which the highest plasma drug concentration was observed.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Median (Full Range) [hours]
    0.50
    0.50
    0.50
    0.49
    0.48
    0.48
    0.48
    0.48
    0.48
    6. Secondary Outcome
    Title Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®
    Description Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [hours]
    2.63
    (26.4)
    1.75
    (16.6)
    4.51
    (25.7)
    2.10
    (31.0)
    8.65
    (31.0)
    2.00
    (10.4)
    15.6
    (103.1)
    1.79
    (13.9)
    10.5
    (100.6)
    7. Secondary Outcome
    Title Part 1: AUC0-inf of Imipenem in Combination With MK-7655
    Description Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM*hr]
    77.3
    55.0
    101
    66.0
    160
    63.8
    223
    71.8
    71.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.41
    Confidence Interval (2-Sided) 90%
    1.07 to 1.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.53
    Confidence Interval (2-Sided) 90%
    1.17 to 1.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.51
    Confidence Interval (2-Sided) 90%
    1.93 to 3.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 3.10
    Confidence Interval (2-Sided) 90%
    2.39 to 4.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.99
    Confidence Interval (2-Sided) 90%
    0.76 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Part 1: Ceoi of Imipenem in Combination With MK-7655
    Description Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
    Time Frame At 0.5 hours postdose

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 8 6 6
    Geometric Mean (95% Confidence Interval) [µM]
    40.7
    35.3
    45.6
    42.6
    46.9
    35.5
    103
    41.8
    35.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.15
    Confidence Interval (2-Sided) 90%
    0.65 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.07
    Confidence Interval (2-Sided) 90%
    0.61 to 1.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.32
    Confidence Interval (2-Sided) 90%
    0.75 to 2.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.46
    Confidence Interval (2-Sided) 90%
    1.40 to 4.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.86
    Confidence Interval (2-Sided) 90%
    0.49 to 1.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Part 1: CLpred of Imipenem in Combination With MK-7655
    Description Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [mL/min]
    180
    253
    138
    211
    87.0
    218
    62.5
    194
    195
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.71
    Confidence Interval (2-Sided) 90%
    0.54 to 0.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.65
    Confidence Interval (2-Sided) 90%
    0.50 to 0.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.40
    Confidence Interval (2-Sided) 90%
    0.31 to 0.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.32
    Confidence Interval (2-Sided) 90%
    0.25 to 0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.01
    Confidence Interval (2-Sided) 90%
    0.78 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Part 1: VZpred of Imipenem in Combination With MK-7655
    Description Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [liters (L)]
    21.1
    26.1
    22.3
    23.4
    20.0
    24.8
    20.5
    24.9
    63.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.81
    Confidence Interval (2-Sided) 90%
    0.61 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.95
    Confidence Interval (2-Sided) 90%
    0.72 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.80
    Confidence Interval (2-Sided) 90%
    0.61 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.83
    Confidence Interval (2-Sided) 90%
    0.63 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.54
    Confidence Interval (2-Sided) 90%
    1.93 to 3.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Part 1: Tmax of Imipenem in Combination With MK-7655
    Description Tmax is the time at which the highest plasma drug concentration was observed.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Median (Full Range) [hours]
    0.50
    0.50
    0.49
    0.48
    0.48
    0.48
    0.48
    0.48
    0.48
    12. Secondary Outcome
    Title Part 1: Apparent t½ of Imipenem in Combination With MK-7655
    Description 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%.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [hours]
    1.54
    (15.2)
    1.24
    (10.8)
    2.18
    (12.8)
    1.40
    (21.1)
    2.78
    (11.9)
    1.32
    (5.8)
    3.24
    (18.7)
    1.21
    (13.7)
    3.20
    (47.8)
    13. Secondary Outcome
    Title Part 1: AUC0-inf of Cilastin in Combination With MK-7655
    Description Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM*hr]
    71.7
    44.8
    100.0
    53.6
    300
    53.7
    777
    56.5
    205
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.60
    Confidence Interval (2-Sided) 90%
    1.03 to 2.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.86
    Confidence Interval (2-Sided) 90%
    1.21 to 2.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 5.60
    Confidence Interval (2-Sided) 90%
    3.64 to 8.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 13.75
    Confidence Interval (2-Sided) 90%
    8.96 to 21.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 3.64
    Confidence Interval (2-Sided) 90%
    2.32 to 5.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Part 1: Ceoi of Cilastin in Combination With MK-7655
    Description Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
    Time Frame At 0.5 hours postdose

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 8 6 6
    Geometric Mean (95% Confidence Interval) [µM]
    43.4
    34.8
    48.7
    42.9
    53.3
    35.8
    111
    44.5
    41.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.25
    Confidence Interval (2-Sided) 90%
    0.75 to 2.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.13
    Confidence Interval (2-Sided) 90%
    0.69 to 1.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.49
    Confidence Interval (2-Sided) 90%
    0.90 to 2.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.49
    Confidence Interval (2-Sided) 90%
    1.51 to 4.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.94
    Confidence Interval (2-Sided) 90%
    0.57 to 1.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Part 1: CLpred of Cilastin in Combination With MK-7655
    Description Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [mL/min]
    162
    259
    116
    217
    38.7
    217
    15.0
    206
    56.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.63
    Confidence Interval (2-Sided) 90%
    0.40 to 0.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.54
    Confidence Interval (2-Sided) 90%
    0.35 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.18
    Confidence Interval (2-Sided) 90%
    0.12 to 0.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.07
    Confidence Interval (2-Sided) 90%
    0.05 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.27
    Confidence Interval (2-Sided) 90%
    0.18 to 0.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Part 1: VZpred of Cilastin in Combination With MK-7655
    Description Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [liters (L)]
    19.2
    23.9
    19.4
    21.4
    16.9
    21.2
    15.9
    21.0
    59.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.80
    Confidence Interval (2-Sided) 90%
    0.62 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel D: Healthy Controls to Panel C
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.91
    Confidence Interval (2-Sided) 90%
    0.71 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel E: Severe Renal Impairment, Panel F: Healthy Controls to Panel E
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.80
    Confidence Interval (2-Sided) 90%
    0.62 to 1.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Panel G: ESRD/HD Period 1 Postdialysis, Panel H: Healthy Controls to Panel G
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.76
    Confidence Interval (2-Sided) 90%
    0.59 to 0.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Panel H: Healthy Controls to Panel G, Panel G: ESRD/HD Period 2 Predialysis
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 2.81
    Confidence Interval (2-Sided) 90%
    2.16 to 3.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Part 1: Tmax of Cilastin in Combination With MK-7655
    Description Tmax is the time at which the highest plasma drug concentration was observed.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Median (Full Range) [hours]
    0.50
    0.50
    0.49
    0.48
    0.48
    0.48
    0.48
    0.48
    0.48
    18. Secondary Outcome
    Title Part 1: Apparent t½ of Cilastin in Combination With MK-7655
    Description 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%.
    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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel H: Healthy Controls to Panel G Panel G: ESRD/HD Period 2 Predialysis
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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). Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. 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).
    Measure Participants 6 6 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [hours]
    1.43
    (31.9)
    1.08
    (27.8)
    2.11
    (20.5)
    1.19
    (28.5)
    5.08
    (59.2)
    1.09
    (10.7)
    12.2
    (118.5)
    1.14
    (26.1)
    12.2
    (131.5)
    19. Secondary Outcome
    Title Part 1: Renal Clearance (CLR) of MK-7655 in Urine
    Description CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
    Time Frame Predose to 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with urine samples 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, Panel G was not sampled due to limitations in producing urine and was thus not included in the analysis.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [mL/min]
    69.8
    (16.5)
    118
    (19.8)
    38.4
    (28.8)
    110
    (36)
    22.3
    (47.2)
    107
    (20.9)
    110
    (20)
    20. Secondary Outcome
    Title Part 1: CLR of Imipenem in Urine
    Description CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
    Time Frame Predose to 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with urine samples 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, Panel G was not sampled due to limitations in producing urine and was thus not included in the analysis.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [mL/min]
    75.0
    (14.6)
    115
    (18.4)
    41.1
    (23.8)
    109
    (29.2)
    17.4
    (44.7)
    104
    (10.5)
    99.1
    (22.3)
    21. Secondary Outcome
    Title Part 1: CLR of Cilastin in Urine
    Description CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
    Time Frame Predose to 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with urine samples 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, Panel G was not sampled due to limitations in producing urine and was thus not included in the analysis.
    Arm/Group Title Panel A: Mild Renal Impairment Panel B: Healthy Controls to Panel A Panel C: Moderate Renal Impairment Panel D: Healthy Controls to Panel C Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel A and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel C and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 6 6 6 6 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [mL/min]
    99.4
    (29.1)
    144
    (21.9)
    59.6
    (29.4)
    136
    (23.9)
    24.5
    (50.5)
    140
    (24.4)
    146
    (18.6)
    22. Secondary Outcome
    Title Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2
    Description Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
    Time Frame Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with severe renal deficiency or ESRD and their matched controls (Panels E-H) who complied with the protocol enough to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included. Per protocol, Panels A-D were not included in the analysis.
    Arm/Group Title Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel G: ESRD/HD Period 2 Predialysis Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg in Part 2. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 1 hour predialysis (Period 1) in Part 2. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 24 hours predialysis (Period 2) in Part 2. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM*hr]
    336
    221
    190
    200
    300
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.52
    Confidence Interval (2-Sided) 90%
    1.07 to 2.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.63
    Confidence Interval (2-Sided) 90%
    0.45 to 0.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel D: Healthy Controls to Panel C, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.67
    Confidence Interval (2-Sided) 90%
    0.47 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4
    Description Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
    Time Frame Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with severe renal deficiency or ESRD and their matched controls (Panels E-H) who complied with the protocol enough to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included. Per protocol, Panels A-D were not included in the analysis.
    Arm/Group Title Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel G: ESRD/HD Period 2 Predialysis Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg in Part 2. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 1 hour predialysis (Period 1) in Part 2. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 24 hours predialysis (Period 2) in Part 2. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 6 6 6 6 6
    Geometric Mean (95% Confidence Interval) [µM*hr]
    0.130
    0.121
    0.0681
    0.0700
    0.114
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.07
    Confidence Interval (2-Sided) 90%
    0.63 to 1.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.60
    Confidence Interval (2-Sided) 90%
    0.35 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel D: Healthy Controls to Panel C, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.61
    Confidence Interval (2-Sided) 90%
    0.36 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19
    Description Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
    Time Frame Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

    Outcome Measure Data

    Analysis Population Description
    Treated participants with severe renal deficiency or ESRD and their matched controls (Panels E-H) who complied with the protocol enough to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included. Per protocol, Panels A-D were not included in the analysis.
    Arm/Group Title Panel E: Severe Renal Impairment Panel F: Healthy Controls to Panel E Panel G: ESRD/HD Period 1 Postdialysis Panel G: ESRD/HD Period 2 Predialysis Panel H: Healthy Controls to Panel G
    Arm/Group Description Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg in Part 2. A subset of healthy control participants was matched specifically to participants in Panel E and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 1 hour predialysis (Period 1) in Part 2. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg 24 hours predialysis (Period 2) in Part 2. Healthy control participants were matched specifically to participants in Panel G and received a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
    Measure Participants 4 6 4 6 5
    Geometric Mean (95% Confidence Interval) [µM*hr]
    9.10
    6.20
    4.56
    4.08
    5.03
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Panel A: Mild Renal Impairment, Panel B: Healthy Controls to Panel A
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 1.47
    Confidence Interval (2-Sided) 90%
    0.63 to 3.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Panel C: Moderate Renal Impairment, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.91
    Confidence Interval (2-Sided) 90%
    0.41 to 2.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Panel D: Healthy Controls to Panel C, Panel E: Severe Renal Impairment
    Comments
    Type of Statistical Test Other
    Comments GMR (Renal Impairment/Healthy Control)
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMR
    Estimated Value 0.81
    Confidence Interval (2-Sided) 90%
    0.37 to 1.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    25. Secondary Outcome
    Title Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)
    Description 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.
    Time Frame Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants are included in the safety analysis according to the treatment received. Per protocol, healthy matched controls were pooled for the purpose of the safety analysis.
    Arm/Group Title Panel A: Mild Renal Impairment Panel C: Moderate Renal Impairment Panel E: Severe Renal Impairment Panel G: ESRD/HD Participants Healthy Matched Controls (Part 1) Panel E: Severe Renal Impairment (Part 2) Panel G: ESRD/HD (Part 2) Healthy Matched Controls (Part 2)
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Period 1) and predialysis (Period 2) in Part 1. Healthy matched controls receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV. Data from all of the Healthy Control subsets from Part 1 was pooled for safety analyses. Participants with Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg postdialysis (Period 1) and predialysis (Period 2) in Part 2. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg postdialysis (Period 1) and predialysis (Period 2) in Part 2. Healthy matched controls receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg postdialysis (Period 1) and predialysis (Period 2) in Part 2. Data from all of the Healthy Control subsets from Part 2 was pooled for safety analyses.
    Measure Participants 7 6 6 6 24 6 6 12
    Number [Percentage of Participants]
    28.6
    408.6%
    16.7
    278.3%
    16.7
    278.3%
    33.3
    555%
    0.0
    0%
    33.3
    555%
    33.3
    555%
    0.0
    0%
    26. Primary Outcome
    Title Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
    Description 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.
    Time Frame 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Panel G: ESRD/HD Period 2 Predialysis
    Arm/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).
    Measure Participants 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)
    27. Primary Outcome
    Title Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
    Description 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].
    Time Frame 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

    Outcome Measure Data

    Analysis Population Description
    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 is included in the analysis.
    Arm/Group Title Panel G: ESRD/HD Period 2 Predialysis
    Arm/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).
    Measure Participants 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)

    Adverse Events

    Time Frame Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)
    Adverse Event Reporting Description All enrolled participants are included in the safety analysis according to the treatment received. Per protocol, healthy matched controls were pooled for the purpose of the safety analysis. AEs were reported separately for Panels E, G, and matching controls during Parts 1 and 2.
    Arm/Group Title Panel A: Mild Renal Impairment Panel C: Moderate Renal Impairment Panel E: Severe Renal Impairment Panel G: ESRD/HD Participants Healthy Matched Controls Panel E: Severe Renal Impairment (Part 2) Panel G: ESRD/HC (Part 2) Healthy Matched Controls (Part 2)
    Arm/Group Description Participants with an eGFR of >50 to <80 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR of 30 to 50 mL/min/1.73m² receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. Participants with an eGFR <30 mL/min/1.73m² 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. 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). Healthy matched controls receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. For AE reporting, all healthy control participants in Part 1 are pooled into a single arm. Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. Healthy matched controls receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg in Part 2. For AE reporting, all healthy control participants in Part 2 are pooled into a single arm.
    All Cause Mortality
    Panel A: Mild Renal Impairment Panel C: Moderate Renal Impairment Panel E: Severe Renal Impairment Panel G: ESRD/HD Participants Healthy Matched Controls Panel E: Severe Renal Impairment (Part 2) Panel G: ESRD/HC (Part 2) Healthy Matched Controls (Part 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Serious Adverse Events
    Panel A: Mild Renal Impairment Panel C: Moderate Renal Impairment Panel E: Severe Renal Impairment Panel G: ESRD/HD Participants Healthy Matched Controls Panel E: Severe Renal Impairment (Part 2) Panel G: ESRD/HC (Part 2) Healthy Matched Controls (Part 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    Panel A: Mild Renal Impairment Panel C: Moderate Renal Impairment Panel E: Severe Renal Impairment Panel G: ESRD/HD Participants Healthy Matched Controls Panel E: Severe Renal Impairment (Part 2) Panel G: ESRD/HC (Part 2) Healthy Matched Controls (Part 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/7 (28.6%) 1/6 (16.7%) 1/6 (16.7%) 2/6 (33.3%) 0/24 (0%) 2/6 (33.3%) 2/6 (33.3%) 0/12 (0%)
    Blood and lymphatic system disorders
    Anaemia 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 1/6 (16.7%) 0/6 (0%) 0/12 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/7 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Diarrhoea 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Nausea 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    General disorders
    Infusion site swelling 1/7 (14.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Investigations
    Alanine aminotransferase increased 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Aspartate aminotransferase increased 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Musculoskeletal discomfort 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 0/6 (0%) 0/12 (0%)
    Nervous system disorders
    Headache 1/7 (14.3%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Somnolence 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 1/6 (16.7%) 0/6 (0%) 0/12 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Nasal congestion 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Oropharyngeal pain 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Wheezing 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)
    Skin and subcutaneous tissue disorders
    Night sweats 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%) 0/6 (0%) 1/6 (16.7%) 0/12 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT01275170
    Other Study ID Numbers:
    • 7655-005
    First Posted:
    Jan 12, 2011
    Last Update Posted:
    Jun 11, 2020
    Last Verified:
    May 1, 2020