Phase 1
N=49
A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005)
Infectious Disease
Bottom Line
View on ClinicalTrials.gov: NCT01275170 ↗Enrolled (actual)
49
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® — 73.5; 45.0; 115; 52.3 µM*hr
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-7655 (Drug); Imipenem + Cilastatin (Drug); Caffeine (Drug); Midazolam (Drug); Omeprazole (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Mar 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® |
73.5; 45.0; 115; 52.3; 236; 48.5 | — |
| PRIMARY Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) |
172; 158; 170; 166; 171; 177 | — |
| PRIMARY Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) |
73; 67; 73; 71; 73; 76 | — |
| SECONDARY Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® |
22.4; 20.4; 23.5; 22.5; 23.6; 18.1 | — |
| SECONDARY Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® |
81.3; 133; 52.1; 114; 25.3; 123 | — |
| SECONDARY Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® |
21.4; 21.6; 22.2; 21.9; 20.1; 22.4 | — |
| SECONDARY Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® |
0.50; 0.50; 0.50; 0.49; 0.48; 0.48 | — |
| SECONDARY Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® |
2.63; 1.75; 4.51; 2.10; 8.65; 2.00 | — |
| SECONDARY Part 1: AUC0-inf of Imipenem in Combination With MK-7655 |
77.3; 55.0; 101; 66.0; 160; 63.8 | — |
| SECONDARY Part 1: Ceoi of Imipenem in Combination With MK-7655 |
40.7; 35.3; 45.6; 42.6; 46.9; 35.5 | — |
| SECONDARY Part 1: CLpred of Imipenem in Combination With MK-7655 |
180; 253; 138; 211; 87.0; 218 | — |
| SECONDARY Part 1: VZpred of Imipenem in Combination With MK-7655 |
21.1; 26.1; 22.3; 23.4; 20.0; 24.8 | — |
| SECONDARY Part 1: Tmax of Imipenem in Combination With MK-7655 |
0.50; 0.50; 0.49; 0.48; 0.48; 0.48 | — |
| SECONDARY Part 1: Apparent t½ of Imipenem in Combination With MK-7655 |
1.54; 1.24; 2.18; 1.40; 2.78; 1.32 | — |
| SECONDARY Part 1: AUC0-inf of Cilastin in Combination With MK-7655 |
71.7; 44.8; 100.0; 53.6; 300; 53.7 | — |
| SECONDARY Part 1: Ceoi of Cilastin in Combination With MK-7655 |
43.4; 34.8; 48.7; 42.9; 53.3; 35.8 | — |
| SECONDARY Part 1: CLpred of Cilastin in Combination With MK-7655 |
162; 259; 116; 217; 38.7; 217 | — |
| SECONDARY Part 1: VZpred of Cilastin in Combination With MK-7655 |
19.2; 23.9; 19.4; 21.4; 16.9; 21.2 | — |
| SECONDARY Part 1: Tmax of Cilastin in Combination With MK-7655 |
0.50; 0.50; 0.49; 0.48; 0.48; 0.48 | — |
| SECONDARY Part 1: Apparent t½ of Cilastin in Combination With MK-7655 |
1.43; 1.08; 2.11; 1.19; 5.08; 1.09 | — |
| SECONDARY Part 1: Renal Clearance (CLR) of MK-7655 in Urine |
69.8; 118; 38.4; 110; 22.3; 107 | — |
| SECONDARY Part 1: CLR of Imipenem in Urine |
75.0; 115; 41.1; 109; 17.4; 104 | — |
| SECONDARY Part 1: CLR of Cilastin in Urine |
99.4; 144; 59.6; 136; 24.5; 140 | — |
| SECONDARY Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 |
336; 221; 190; 200; 300 | — |
| SECONDARY Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 |
0.130; 0.121; 0.0681; 0.0700; 0.114 | — |
| SECONDARY Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 |
9.10; 6.20; 4.56; 4.08; 5.03 | — |
| SECONDARY Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) |
28.6; 16.7; 16.7; 33.3; 0.0; 33.3 | — |
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.
Eligibility Criteria
Inclusion criteria
- Participants of reproductive potential (male or female) must be willing to use contraception.
- Body Mass Index (BMI) ≤40 kg/m^2
- Weight >60 kg at screening visit
- No clinically significant abnormality on electrocardiogram (ECG) at screening visit and/or prior to administration of the initial dose of study drug
- Panels A-D: smokers will be limited to no more that 10 cigarettes per day.
- Panels E-H: nonsmoker or has not used nicotine for at least 6 months
- In good health (stable health for participants with renal impairment)
Exclusion criteria
- Pregnant or breastfeeding.
- History of recent stroke, chronic seizures, or major neurological disorder
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary abnormalities or diseases
- History of malignant neoplastic disease. Exceptions: (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix; (2) other malignancies that have been successfully treated ≥10 years prior to the screening visit
- Panels A-D: Use of any medication (prescription or non-prescription) or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug to the post study visit
- Panels E-H: Use of any medication (prescription or non-prescription) or herbal remedies (such as St. John's Wort [Hypericum perforatum]) that are inhibitors or inducers of CYP1A2, CYP2C19, CYP34A, or substrates of CYP2C19, beginning approximately 2 weeks (or 5 half-lives) prior to administration of the probe cocktail, until the post-study visit
- Consumption of greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
- Consumption of greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
- Major surgery, donation or loss of 1 unit of blood (approximately 500 mL), or participation in another investigational study within 4 weeks prior to the screening visit
- History of multiple and/or severe allergies (including latex allergy), or prior anaphylactic reaction or intolerability to prescription or non-prescription drugs or food
- History of hypersensitivity to PRIMAXIN® IV or other beta lactam antibiotic (including but not limited to penicillins, cephalosporins, monobactams and carbapenems)
- Regular user (including recreational use of drugs [including alcohol]) within approximately 12 months of screening visit
- History of kidney removal and/or renal transplant
- History of Clostridium difficile colitis or known C. difficile colonization
Data sourced from ClinicalTrials.gov (NCT01275170). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.