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Completed

NCT Number: NCT01275170

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

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.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MK-7655

Drug

125 mg intravenous (IV) over 30 minutes as a single dose

Other names: RELEBACTAM®

Imipenem + Cilastatin

Drug

250 mg IV over 30 minutes as a single dose

Other names: PRIMAXIN®

Caffeine

Drug

Caffeine caplet, single 200 mg dose, orally

Other names: No Doz®

midazolam

Drug

Midazolam hcl syrup single 2.0 mg dose by mouth.

Other names: VERSED®

Omeprazole

Drug

Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally

Other names: PRILOSEC®

Primary outcomes

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

    Time frame: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

    AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.

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

    Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

    The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)*QB*[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)] where QB=350 mL/min and Hct=hematocrit.

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

    Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

    The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS[100*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration].

Secondary outcomes

  1. Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®

    Time frame: 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®

    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

    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®

    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

    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®

    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

    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®

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    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

    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

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    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

    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

    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

    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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Jan 12, 2011
Registry last updated
Jun 11, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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