Infectious Disease
Conditions
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.
Interventions
DRUGMK-7655
125 mg intravenous (IV) over 30 minutes as a single dose
250 mg IV over 30 minutes as a single dose
DRUGCaffeine
Caffeine caplet, single 200 mg dose, orally
DRUGMidazolam
Midazolam hcl syrup single 2.0 mg dose by mouth.
DRUGOmeprazole
Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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%. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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%. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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%. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
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 details
All panels participated in Part 1 of the study. Panels E to H also participated in Part 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: Mild Renal Impairment 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. | 7 |
| Panel B: Healthy Controls to Panel A 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. | 6 |
| Panel C: Moderate Renal Impairment 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. | 6 |
| Panel D: Healthy Controls to Panel C 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. | 6 |
| Panel E: Severe Renal Impairment 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. | 6 |
| Panel F: Healthy Controls to Panel E 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. | 6 |
| Panel G: ESRD/HD Participants 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). | 6 |
| Panel H: Healthy Controls to Panel G 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. | 6 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 1: Period 1 | Equipment malfunction before study drug | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 71.1 Years STANDARD_DEVIATION 3.4 | 64.5 Years STANDARD_DEVIATION 3.9 | 68.3 Years STANDARD_DEVIATION 5 | 64.2 Years STANDARD_DEVIATION 5.7 | 62.8 Years STANDARD_DEVIATION 7.5 | 60.5 Years STANDARD_DEVIATION 6.4 | 44.5 Years STANDARD_DEVIATION 7.9 | 41.5 Years STANDARD_DEVIATION 11.5 | 59.9 Years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 21 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 | 0 / 6 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 2 / 7 | 1 / 6 | 1 / 6 | 2 / 6 | 0 / 24 | 2 / 6 | 2 / 6 | 0 / 12 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 | 0 / 6 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)\*QB\*\[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)\] where QB=350 mL/min and Hct=hematocrit.
Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 1 hour postdose | 172 mL/min | Geometric Coefficient of Variation 3.5 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 1.5 hours postdose | 158 mL/min | Geometric Coefficient of Variation 9.4 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 2 hours postdose | 170 mL/min | Geometric Coefficient of Variation 5.9 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 2.5 hours postdose | 166 mL/min | Geometric Coefficient of Variation 7 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 3.0 hours postdose | 171 mL/min | Geometric Coefficient of Variation 5.4 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 3.5 hours postdose | 177 mL/min | Geometric Coefficient of Variation 15.7 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 4 hours postdose | 204 mL/min | Geometric Coefficient of Variation 20.2 |
| Panel A: Mild Renal Impairment | Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 4.5 hours postdose | 198 mL/min | Geometric Coefficient of Variation 23 |
Primary
Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS\[100\*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration\].
Time frame: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 1 hour postdose | 73 Extraction coefficient | Geometric Coefficient of Variation 1.8 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 1.5 hours postdose | 67 Extraction coefficient | Geometric Coefficient of Variation 9.5 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 2 hours postdose | 73 Extraction coefficient | Geometric Coefficient of Variation 4.5 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 2.5 hours postdose | 71 Extraction coefficient | Geometric Coefficient of Variation 5.6 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 3.0 hours postdose | 73 Extraction coefficient | Geometric Coefficient of Variation 4.1 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 3.5 hours postdose | 76 Extraction coefficient | Geometric Coefficient of Variation 15.7 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 4 hours postdose | 87 Extraction coefficient | Geometric Coefficient of Variation 19.6 |
| Panel A: Mild Renal Impairment | Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | 4.5 hours postdose | 84 Extraction coefficient | Geometric Coefficient of Variation 22.2 |
Primary
Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 73.5 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 45.0 µM*hr |
| Panel C: Moderate Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 115 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 52.3 µM*hr |
| Panel E: Severe Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 236 µM*hr |
| Panel F: Healthy Controls to Panel E | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 48.5 µM*hr |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 414 µM*hr |
| Panel H: Healthy Controls to Panel G | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 44.5 µM*hr |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN® | 78.0 µM*hr |
90% CI: [1.12, 2.39]
90% CI: [1.51, 3.18]
90% CI: [3.37, 7.04]
90% CI: [6.45, 13.46]
90% CI: [1.2, 2.58]
Secondary
Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®
Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 2.63 hours | Geometric Coefficient of Variation 26.4 |
| Panel B: Healthy Controls to Panel A | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 1.75 hours | Geometric Coefficient of Variation 16.6 |
| Panel C: Moderate Renal Impairment | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 4.51 hours | Geometric Coefficient of Variation 25.7 |
| Panel D: Healthy Controls to Panel C | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 2.10 hours | Geometric Coefficient of Variation 31 |
| Panel E: Severe Renal Impairment | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 8.65 hours | Geometric Coefficient of Variation 31 |
| Panel F: Healthy Controls to Panel E | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 2.00 hours | Geometric Coefficient of Variation 10.4 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 15.6 hours | Geometric Coefficient of Variation 103.1 |
| Panel H: Healthy Controls to Panel G | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 1.79 hours | Geometric Coefficient of Variation 13.9 |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | 10.5 hours | Geometric Coefficient of Variation 100.6 |
Secondary
Part 1: Apparent t½ of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 1.43 hours | Geometric Coefficient of Variation 31.9 |
| Panel B: Healthy Controls to Panel A | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 1.08 hours | Geometric Coefficient of Variation 27.8 |
| Panel C: Moderate Renal Impairment | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 2.11 hours | Geometric Coefficient of Variation 20.5 |
| Panel D: Healthy Controls to Panel C | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 1.19 hours | Geometric Coefficient of Variation 28.5 |
| Panel E: Severe Renal Impairment | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 5.08 hours | Geometric Coefficient of Variation 59.2 |
| Panel F: Healthy Controls to Panel E | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 1.09 hours | Geometric Coefficient of Variation 10.7 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 12.2 hours | Geometric Coefficient of Variation 118.5 |
| Panel H: Healthy Controls to Panel G | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 1.14 hours | Geometric Coefficient of Variation 26.1 |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | 12.2 hours | Geometric Coefficient of Variation 131.5 |
Secondary
Part 1: Apparent t½ of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 1.54 hours | Geometric Coefficient of Variation 15.2 |
| Panel B: Healthy Controls to Panel A | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 1.24 hours | Geometric Coefficient of Variation 10.8 |
| Panel C: Moderate Renal Impairment | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 2.18 hours | Geometric Coefficient of Variation 12.8 |
| Panel D: Healthy Controls to Panel C | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 1.40 hours | Geometric Coefficient of Variation 21.1 |
| Panel E: Severe Renal Impairment | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 2.78 hours | Geometric Coefficient of Variation 11.9 |
| Panel F: Healthy Controls to Panel E | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 1.32 hours | Geometric Coefficient of Variation 5.8 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 3.24 hours | Geometric Coefficient of Variation 18.7 |
| Panel H: Healthy Controls to Panel G | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 1.21 hours | Geometric Coefficient of Variation 13.7 |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | 3.20 hours | Geometric Coefficient of Variation 47.8 |
Secondary
Part 1: AUC0-inf of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 71.7 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 44.8 µM*hr |
| Panel C: Moderate Renal Impairment | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 100.0 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 53.6 µM*hr |
| Panel E: Severe Renal Impairment | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 300 µM*hr |
| Panel F: Healthy Controls to Panel E | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 53.7 µM*hr |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 777 µM*hr |
| Panel H: Healthy Controls to Panel G | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 56.5 µM*hr |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | 205 µM*hr |
90% CI: [1.03, 2.49]
90% CI: [1.21, 2.87]
90% CI: [3.64, 8.59]
90% CI: [8.96, 21.12]
90% CI: [2.32, 5.69]
Secondary
Part 1: AUC0-inf of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 77.3 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 55.0 µM*hr |
| Panel C: Moderate Renal Impairment | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 101 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 66.0 µM*hr |
| Panel E: Severe Renal Impairment | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 160 µM*hr |
| Panel F: Healthy Controls to Panel E | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 63.8 µM*hr |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 223 µM*hr |
| Panel H: Healthy Controls to Panel G | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 71.8 µM*hr |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | 71.2 µM*hr |
90% CI: [1.07, 1.84]
90% CI: [1.17, 1.99]
90% CI: [1.93, 3.26]
90% CI: [2.39, 4.03]
90% CI: [0.76, 1.29]
Secondary
Part 1: Ceoi of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
Time frame: At 0.5 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 43.4 µM |
| Panel B: Healthy Controls to Panel A | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 34.8 µM |
| Panel C: Moderate Renal Impairment | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 48.7 µM |
| Panel D: Healthy Controls to Panel C | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 42.9 µM |
| Panel E: Severe Renal Impairment | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 53.3 µM |
| Panel F: Healthy Controls to Panel E | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 35.8 µM |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 111 µM |
| Panel H: Healthy Controls to Panel G | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 44.5 µM |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Ceoi of Cilastin in Combination With MK-7655 | 41.7 µM |
90% CI: [0.75, 2.08]
90% CI: [0.69, 1.87]
90% CI: [0.9, 2.44]
90% CI: [1.51, 4.09]
90% CI: [0.57, 1.54]
Secondary
Part 1: Ceoi of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion.
Time frame: At 0.5 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 40.7 µM |
| Panel B: Healthy Controls to Panel A | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 35.3 µM |
| Panel C: Moderate Renal Impairment | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 45.6 µM |
| Panel D: Healthy Controls to Panel C | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 42.6 µM |
| Panel E: Severe Renal Impairment | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 46.9 µM |
| Panel F: Healthy Controls to Panel E | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 35.5 µM |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 103 µM |
| Panel H: Healthy Controls to Panel G | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 41.8 µM |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Ceoi of Imipenem in Combination With MK-7655 | 35.9 µM |
90% CI: [0.65, 2.06]
90% CI: [0.61, 1.89]
90% CI: [0.75, 2.32]
90% CI: [1.4, 4.33]
90% CI: [0.49, 1.51]
Secondary
Part 1: CLpred of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: CLpred of Cilastin in Combination With MK-7655 | 162 mL/min |
| Panel B: Healthy Controls to Panel A | Part 1: CLpred of Cilastin in Combination With MK-7655 | 259 mL/min |
| Panel C: Moderate Renal Impairment | Part 1: CLpred of Cilastin in Combination With MK-7655 | 116 mL/min |
| Panel D: Healthy Controls to Panel C | Part 1: CLpred of Cilastin in Combination With MK-7655 | 217 mL/min |
| Panel E: Severe Renal Impairment | Part 1: CLpred of Cilastin in Combination With MK-7655 | 38.7 mL/min |
| Panel F: Healthy Controls to Panel E | Part 1: CLpred of Cilastin in Combination With MK-7655 | 217 mL/min |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: CLpred of Cilastin in Combination With MK-7655 | 15.0 mL/min |
| Panel H: Healthy Controls to Panel G | Part 1: CLpred of Cilastin in Combination With MK-7655 | 206 mL/min |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: CLpred of Cilastin in Combination With MK-7655 | 56.6 mL/min |
90% CI: [0.4, 0.97]
90% CI: [0.35, 0.83]
90% CI: [0.12, 0.27]
90% CI: [0.05, 0.11]
90% CI: [0.18, 0.43]
Secondary
Part 1: CLpred of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: CLpred of Imipenem in Combination With MK-7655 | 180 mL/min |
| Panel B: Healthy Controls to Panel A | Part 1: CLpred of Imipenem in Combination With MK-7655 | 253 mL/min |
| Panel C: Moderate Renal Impairment | Part 1: CLpred of Imipenem in Combination With MK-7655 | 138 mL/min |
| Panel D: Healthy Controls to Panel C | Part 1: CLpred of Imipenem in Combination With MK-7655 | 211 mL/min |
| Panel E: Severe Renal Impairment | Part 1: CLpred of Imipenem in Combination With MK-7655 | 87.0 mL/min |
| Panel F: Healthy Controls to Panel E | Part 1: CLpred of Imipenem in Combination With MK-7655 | 218 mL/min |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: CLpred of Imipenem in Combination With MK-7655 | 62.5 mL/min |
| Panel H: Healthy Controls to Panel G | Part 1: CLpred of Imipenem in Combination With MK-7655 | 194 mL/min |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: CLpred of Imipenem in Combination With MK-7655 | 195 mL/min |
90% CI: [0.54, 0.93]
90% CI: [0.5, 0.85]
90% CI: [0.31, 0.52]
90% CI: [0.25, 0.42]
90% CI: [0.78, 1.31]
Secondary
Part 1: CLR of Cilastin in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Time frame: Predose to 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: CLR of Cilastin in Urine | 99.4 mL/min | Geometric Coefficient of Variation 29.1 |
| Panel B: Healthy Controls to Panel A | Part 1: CLR of Cilastin in Urine | 144 mL/min | Geometric Coefficient of Variation 21.9 |
| Panel C: Moderate Renal Impairment | Part 1: CLR of Cilastin in Urine | 59.6 mL/min | Geometric Coefficient of Variation 29.4 |
| Panel D: Healthy Controls to Panel C | Part 1: CLR of Cilastin in Urine | 136 mL/min | Geometric Coefficient of Variation 23.9 |
| Panel E: Severe Renal Impairment | Part 1: CLR of Cilastin in Urine | 24.5 mL/min | Geometric Coefficient of Variation 50.5 |
| Panel F: Healthy Controls to Panel E | Part 1: CLR of Cilastin in Urine | 140 mL/min | Geometric Coefficient of Variation 24.4 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: CLR of Cilastin in Urine | 146 mL/min | Geometric Coefficient of Variation 18.6 |
Secondary
Part 1: CLR of Imipenem in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Time frame: Predose to 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: CLR of Imipenem in Urine | 75.0 mL/min | Geometric Coefficient of Variation 14.6 |
| Panel B: Healthy Controls to Panel A | Part 1: CLR of Imipenem in Urine | 115 mL/min | Geometric Coefficient of Variation 18.4 |
| Panel C: Moderate Renal Impairment | Part 1: CLR of Imipenem in Urine | 41.1 mL/min | Geometric Coefficient of Variation 23.8 |
| Panel D: Healthy Controls to Panel C | Part 1: CLR of Imipenem in Urine | 109 mL/min | Geometric Coefficient of Variation 29.2 |
| Panel E: Severe Renal Impairment | Part 1: CLR of Imipenem in Urine | 17.4 mL/min | Geometric Coefficient of Variation 44.7 |
| Panel F: Healthy Controls to Panel E | Part 1: CLR of Imipenem in Urine | 104 mL/min | Geometric Coefficient of Variation 10.5 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: CLR of Imipenem in Urine | 99.1 mL/min | Geometric Coefficient of Variation 22.3 |
Secondary
Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®
Ceoi is the observed plasma drug concentration at the end of IV infusion.
Time frame: At 0.5 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 22.4 µM |
| Panel B: Healthy Controls to Panel A | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 20.4 µM |
| Panel C: Moderate Renal Impairment | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 23.5 µM |
| Panel D: Healthy Controls to Panel C | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 22.5 µM |
| Panel E: Severe Renal Impairment | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 23.6 µM |
| Panel F: Healthy Controls to Panel E | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 18.1 µM |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 53.1 µM |
| Panel H: Healthy Controls to Panel G | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 22.7 µM |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN® | 19.3 µM |
90% CI: [0.64, 1.88]
90% CI: [0.62, 1.77]
90% CI: [0.77, 2.2]
90% CI: [1.39, 3.96]
90% CI: [0.5, 1.44]
Secondary
Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 81.3 mL/min |
| Panel B: Healthy Controls to Panel A | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 133 mL/min |
| Panel C: Moderate Renal Impairment | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 52.1 mL/min |
| Panel D: Healthy Controls to Panel C | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 114 mL/min |
| Panel E: Severe Renal Impairment | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 25.3 mL/min |
| Panel F: Healthy Controls to Panel E | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 123 mL/min |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 14.4 mL/min |
| Panel H: Healthy Controls to Panel G | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 135 mL/min |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | 76.6 mL/min |
90% CI: [0.42, 0.9]
90% CI: [0.31, 0.66]
90% CI: [0.14, 0.3]
90% CI: [0.07, 0.16]
90% CI: [0.39, 0.84]
Secondary
Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®
VZpred is the predicted volume of distribution during the terminal phase.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 21.4 liters (L) |
| Panel B: Healthy Controls to Panel A | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 21.6 liters (L) |
| Panel C: Moderate Renal Impairment | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 22.2 liters (L) |
| Panel D: Healthy Controls to Panel C | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 21.9 liters (L) |
| Panel E: Severe Renal Impairment | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 20.1 liters (L) |
| Panel F: Healthy Controls to Panel E | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 22.4 liters (L) |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 16.2 liters (L) |
| Panel H: Healthy Controls to Panel G | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 17.0 liters (L) |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | 55.7 liters (L) |
90% CI: [0.82, 1.21]
90% CI: [0.84, 1.22]
90% CI: [0.74, 1.08]
90% CI: [0.79, 1.16]
90% CI: [2.7, 4]
Secondary
Part 1: Renal Clearance (CLR) of MK-7655 in Urine
CLR represents renal clearance in urine. Urine was collected for 24 hours postdose.
Time frame: Predose to 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 69.8 mL/min | Geometric Coefficient of Variation 16.5 |
| Panel B: Healthy Controls to Panel A | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 118 mL/min | Geometric Coefficient of Variation 19.8 |
| Panel C: Moderate Renal Impairment | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 38.4 mL/min | Geometric Coefficient of Variation 28.8 |
| Panel D: Healthy Controls to Panel C | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 110 mL/min | Geometric Coefficient of Variation 36 |
| Panel E: Severe Renal Impairment | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 22.3 mL/min | Geometric Coefficient of Variation 47.2 |
| Panel F: Healthy Controls to Panel E | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 107 mL/min | Geometric Coefficient of Variation 20.9 |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | 110 mL/min | Geometric Coefficient of Variation 20 |
Secondary
Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®
Tmax is the time at which the highest plasma drug concentration was observed.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.50 hours |
| Panel B: Healthy Controls to Panel A | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.50 hours |
| Panel C: Moderate Renal Impairment | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.50 hours |
| Panel D: Healthy Controls to Panel C | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.49 hours |
| Panel E: Severe Renal Impairment | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.48 hours |
| Panel F: Healthy Controls to Panel E | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.48 hours |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.48 hours |
| Panel H: Healthy Controls to Panel G | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.48 hours |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | 0.48 hours |
Secondary
Part 1: Tmax of Cilastin in Combination With MK-7655
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.50 hours |
| Panel B: Healthy Controls to Panel A | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.50 hours |
| Panel C: Moderate Renal Impairment | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.49 hours |
| Panel D: Healthy Controls to Panel C | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
| Panel E: Severe Renal Impairment | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
| Panel F: Healthy Controls to Panel E | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
| Panel H: Healthy Controls to Panel G | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Tmax of Cilastin in Combination With MK-7655 | 0.48 hours |
Secondary
Part 1: Tmax of Imipenem in Combination With MK-7655
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.50 hours |
| Panel B: Healthy Controls to Panel A | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.50 hours |
| Panel C: Moderate Renal Impairment | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.49 hours |
| Panel D: Healthy Controls to Panel C | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
| Panel E: Severe Renal Impairment | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
| Panel F: Healthy Controls to Panel E | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
| Panel H: Healthy Controls to Panel G | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: Tmax of Imipenem in Combination With MK-7655 | 0.48 hours |
Secondary
Part 1: VZpred of Cilastin in Combination With MK-7655
Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: VZpred of Cilastin in Combination With MK-7655 | 19.2 liters (L) |
| Panel B: Healthy Controls to Panel A | Part 1: VZpred of Cilastin in Combination With MK-7655 | 23.9 liters (L) |
| Panel C: Moderate Renal Impairment | Part 1: VZpred of Cilastin in Combination With MK-7655 | 19.4 liters (L) |
| Panel D: Healthy Controls to Panel C | Part 1: VZpred of Cilastin in Combination With MK-7655 | 21.4 liters (L) |
| Panel E: Severe Renal Impairment | Part 1: VZpred of Cilastin in Combination With MK-7655 | 16.9 liters (L) |
| Panel F: Healthy Controls to Panel E | Part 1: VZpred of Cilastin in Combination With MK-7655 | 21.2 liters (L) |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: VZpred of Cilastin in Combination With MK-7655 | 15.9 liters (L) |
| Panel H: Healthy Controls to Panel G | Part 1: VZpred of Cilastin in Combination With MK-7655 | 21.0 liters (L) |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: VZpred of Cilastin in Combination With MK-7655 | 59.1 liters (L) |
90% CI: [0.62, 1.04]
90% CI: [0.71, 1.17]
90% CI: [0.62, 1.03]
90% CI: [0.59, 0.97]
90% CI: [2.16, 3.65]
Secondary
Part 1: VZpred of Imipenem in Combination With MK-7655
Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 1: VZpred of Imipenem in Combination With MK-7655 | 21.1 liters (L) |
| Panel B: Healthy Controls to Panel A | Part 1: VZpred of Imipenem in Combination With MK-7655 | 26.1 liters (L) |
| Panel C: Moderate Renal Impairment | Part 1: VZpred of Imipenem in Combination With MK-7655 | 22.3 liters (L) |
| Panel D: Healthy Controls to Panel C | Part 1: VZpred of Imipenem in Combination With MK-7655 | 23.4 liters (L) |
| Panel E: Severe Renal Impairment | Part 1: VZpred of Imipenem in Combination With MK-7655 | 20.0 liters (L) |
| Panel F: Healthy Controls to Panel E | Part 1: VZpred of Imipenem in Combination With MK-7655 | 24.8 liters (L) |
| Panel G: ESRD/HD Period 1 Postdialysis | Part 1: VZpred of Imipenem in Combination With MK-7655 | 20.5 liters (L) |
| Panel H: Healthy Controls to Panel G | Part 1: VZpred of Imipenem in Combination With MK-7655 | 24.9 liters (L) |
| Panel G: ESRD/HD Period 2 Predialysis | Part 1: VZpred of Imipenem in Combination With MK-7655 | 63.3 liters (L) |
90% CI: [0.61, 1.08]
90% CI: [0.72, 1.26]
90% CI: [0.61, 1.06]
90% CI: [0.63, 1.09]
90% CI: [1.93, 3.36]
Secondary
Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2
Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | 336 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | 221 µM*hr |
| Panel C: Moderate Renal Impairment | Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | 190 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | 200 µM*hr |
| Panel E: Severe Renal Impairment | Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | 300 µM*hr |
90% CI: [1.07, 2.15]
90% CI: [0.45, 0.9]
90% CI: [0.47, 0.94]
Secondary
Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4
Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | 0.130 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | 0.121 µM*hr |
| Panel C: Moderate Renal Impairment | Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | 0.0681 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | 0.0700 µM*hr |
| Panel E: Severe Renal Impairment | Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | 0.114 µM*hr |
90% CI: [0.63, 1.83]
90% CI: [0.35, 1.01]
90% CI: [0.36, 1.04]
Secondary
Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19
Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants.
Time frame: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Mild Renal Impairment | Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | 9.10 µM*hr |
| Panel B: Healthy Controls to Panel A | Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | 6.20 µM*hr |
| Panel C: Moderate Renal Impairment | Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | 4.56 µM*hr |
| Panel D: Healthy Controls to Panel C | Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | 4.08 µM*hr |
| Panel E: Severe Renal Impairment | Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | 5.03 µM*hr |
90% CI: [0.63, 3.4]
90% CI: [0.41, 2]
90% CI: [0.37, 1.78]
Secondary
Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Mild Renal Impairment | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 28.6 Percentage of Participants |
| Panel B: Healthy Controls to Panel A | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 16.7 Percentage of Participants |
| Panel C: Moderate Renal Impairment | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 16.7 Percentage of Participants |
| Panel D: Healthy Controls to Panel C | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 33.3 Percentage of Participants |
| Panel E: Severe Renal Impairment | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 0.0 Percentage of Participants |
| Panel F: Healthy Controls to Panel E | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 33.3 Percentage of Participants |
| Panel G: ESRD/HD Period 1 Postdialysis | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 33.3 Percentage of Participants |
| Panel H: Healthy Controls to Panel G | Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | 0.0 Percentage of Participants |