Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panel A Mild Renal Impairment | Experimental | Participants with an eGFR of >50 to <80 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. |
|
| Panel B Healthy Participants | Experimental | A subset of healthy control participants were matched specifically to participants in Panel A and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. |
|
| Panel C Moderate Renal Impairment | Experimental | Participants with an eGFR of 30 to 50 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. |
|
| Panel D Healthy Participants | Experimental | A subset of healthy control participants were matched specifically to participants in Panel C and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. |
|
| Panel E Severe Renal Impairment | Experimental | Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-7655 | Drug | 125 mg intravenous (IV) over 30 minutes as a single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)*QB*[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)] where QB=350 mL/min and Hct=hematocrit. | 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose |
| Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD) | The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS[100*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration]. | 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 0.5 hours postdose |
| Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® |
Not provided
Inclusion criteria
Exclusion criteria
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31856304 | Result | Bhagunde P, Colon-Gonzalez F, Liu Y, Wu J, Xu SS, Garrett G, Jumes P, Lasseter K, Marbury T, Rizk ML, Lala M, Rhee EG, Butterton JR, Boundy K. Impact of renal impairment and human organic anion transporter inhibition on pharmacokinetics, safety and tolerability of relebactam combined with imipenem and cilastatin. Br J Clin Pharmacol. 2020 May;86(5):944-957. doi: 10.1111/bcp.14204. Epub 2020 Jan 23. |
Not provided
Not provided
Not provided
Not provided
Not provided
All panels participated in Part 1 of the study. Panels E to H also participated in Part 2 of the study.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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). |
| FG007 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Period 1 |
|
| |||||||||||||||||||||
| Part 1: Period 2 |
| ||||||||||||||||||||||
| Part 2: Period 1 |
| ||||||||||||||||||||||
| Part 2: Period 2 |
|
The Base Population consists of 49 randomized participants, including n=1 participant in Panel A who was discontinued prior to receiving study drug due to an equipment malfunction.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Panel B: Healthy Controls to Panel A |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v. 15.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003141 | Communicable Diseases |
| ID | Term |
|---|---|
| D007239 | Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C568736 | relebactam |
| D000077728 | Cilastatin, Imipenem Drug Combination |
| D002110 | Caffeine |
| D008874 | Midazolam |
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D015378 | Imipenem |
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Panel F Healthy Participants | Experimental | A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. |
|
| Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD) | Experimental | Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2). |
|
| Panel H Healthy Volunteers | Experimental | A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. |
|
|
| Imipenem + Cilastatin | Drug | 250 mg IV over 30 minutes as a single dose |
|
|
| Caffeine | Drug | Caffeine caplet, single 200 mg dose, orally |
|
|
| Midazolam | Drug | Midazolam hcl syrup single 2.0 mg dose by mouth. |
|
|
| Omeprazole | Drug | Omeprazole tablets, single 40 mg dose (as two 20 mg tablets), orally |
|
|
CLpred is the predicted apparent total body clearance of drug. |
| Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN® | VZpred is the predicted volume of distribution during the terminal phase. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN® | Tmax is the time at which the highest plasma drug concentration was observed. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN® | Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: AUC0-inf of Imipenem in Combination With MK-7655 | Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Ceoi of Imipenem in Combination With MK-7655 | Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion. | At 0.5 hours postdose |
| Part 1: CLpred of Imipenem in Combination With MK-7655 | Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: VZpred of Imipenem in Combination With MK-7655 | Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Tmax of Imipenem in Combination With MK-7655 | Tmax is the time at which the highest plasma drug concentration was observed. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Apparent t½ of Imipenem in Combination With MK-7655 | Imipenem is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: AUC0-inf of Cilastin in Combination With MK-7655 | Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Ceoi of Cilastin in Combination With MK-7655 | Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion. | At 0.5 hours postdose |
| Part 1: CLpred of Cilastin in Combination With MK-7655 | Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: VZpred of Cilastin in Combination With MK-7655 | Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Tmax of Cilastin in Combination With MK-7655 | Tmax is the time at which the highest plasma drug concentration was observed. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Apparent t½ of Cilastin in Combination With MK-7655 | Cilastin is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
| Part 1: Renal Clearance (CLR) of MK-7655 in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | Predose to 24 hours postdose |
| Part 1: CLR of Imipenem in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | Predose to 24 hours postdose |
| Part 1: CLR of Cilastin in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | Predose to 24 hours postdose |
| Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2 | Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
| Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4 | Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
| Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19 | Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
| Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks) |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
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.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | 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). |
| BG007 | 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. |
| BG008 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | Panel G: ESRD/HD Period 1 Postdialysis | 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). |
| OG007 | 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. |
| OG008 | Panel G: ESRD/HD Period 2 Predialysis | 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). |
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM | At 0.5 hours postdose |
|
|
|
|
| Secondary | Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN® | CLpred is the predicted apparent total body clearance of drug. | 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. | Posted | Geometric Mean | 95% Confidence Interval | mL/min | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | liters (L) | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Median | Full Range | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| 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%. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM | At 0.5 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | mL/min | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | liters (L) | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| Secondary | Part 1: Tmax of Imipenem in Combination With MK-7655 | Tmax is the time at which the highest plasma drug concentration was observed. | 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. | Posted | Median | Full Range | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| 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%. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM | At 0.5 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | mL/min | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | liters (L) | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
|
| Secondary | Part 1: Tmax of Cilastin in Combination With MK-7655 | Tmax is the time at which the highest plasma drug concentration was observed. | 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. | Posted | Median | Full Range | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| 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%. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose |
|
|
|
| Secondary | Part 1: Renal Clearance (CLR) of MK-7655 in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Predose to 24 hours postdose |
|
|
|
| Secondary | Part 1: CLR of Imipenem in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Predose to 24 hours postdose |
|
|
|
| Secondary | Part 1: CLR of Cilastin in Urine | CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Predose to 24 hours postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | µM*hr | Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose |
|
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks) |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose |
|
|
|
| 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]. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Extraction coefficient | 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 2 |
| 7 |
| EG001 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | 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). | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Healthy Matched Controls | 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. | 0 | 24 | 0 | 24 | 0 | 24 |
| EG005 | Panel E: Severe Renal Impairment (Part 2) | Participants with an eGFR <30 mL/min/1.73m² receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Panel G: ESRD/HC (Part 2) | Participants with ESRD/HD receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG007 | Healthy Matched Controls (Part 2) | 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. | 0 | 12 | 0 | 12 | 0 | 12 |
| Abdominal pain | Gastrointestinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Infusion site swelling | General disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA v. 15.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA v. 15.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v. 15.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA v. 15.0 | Systematic Assessment |
|
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.
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D015377 | Cilastatin |
| D003521 | Cyclopropanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D011688 | Purinones |
| D011687 | Purines |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |
| GMR |
| 1.04 |
| 2-Sided |
| 90 |
| 0.62 |
| 1.77 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 1.30 | 2-Sided | 90 | 0.77 | 2.20 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 2.34 | 2-Sided | 90 | 1.39 | 3.96 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.85 | 2-Sided | 90 | 0.50 | 1.44 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.46 |
| 2-Sided |
| 90 |
| 0.31 |
| 0.66 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.21 | 2-Sided | 90 | 0.14 | 0.30 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.11 | 2-Sided | 90 | 0.07 | 0.16 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.57 | 2-Sided | 90 | 0.39 | 0.84 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 1.01 |
| 2-Sided |
| 90 |
| 0.84 |
| 1.22 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.90 | 2-Sided | 90 | 0.74 | 1.08 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.96 | 2-Sided | 90 | 0.79 | 1.16 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 3.28 | 2-Sided | 90 | 2.70 | 4.00 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 1.53 |
| 2-Sided |
| 90 |
| 1.17 |
| 1.99 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 2.51 | 2-Sided | 90 | 1.93 | 3.26 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 3.10 | 2-Sided | 90 | 2.39 | 4.03 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.99 | 2-Sided | 90 | 0.76 | 1.29 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 1.07 |
| 2-Sided |
| 90 |
| 0.61 |
| 1.89 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 1.32 | 2-Sided | 90 | 0.75 | 2.32 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 2.46 | 2-Sided | 90 | 1.40 | 4.33 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.86 | 2-Sided | 90 | 0.49 | 1.51 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.65 |
| 2-Sided |
| 90 |
| 0.50 |
| 0.85 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.40 | 2-Sided | 90 | 0.31 | 0.52 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.32 | 2-Sided | 90 | 0.25 | 0.42 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 1.01 | 2-Sided | 90 | 0.78 | 1.31 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.95 |
| 2-Sided |
| 90 |
| 0.72 |
| 1.26 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.80 | 2-Sided | 90 | 0.61 | 1.06 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.83 | 2-Sided | 90 | 0.63 | 1.09 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 2.54 | 2-Sided | 90 | 1.93 | 3.36 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 1.86 |
| 2-Sided |
| 90 |
| 1.21 |
| 2.87 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 5.60 | 2-Sided | 90 | 3.64 | 8.59 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 13.75 | 2-Sided | 90 | 8.96 | 21.12 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 3.64 | 2-Sided | 90 | 2.32 | 5.69 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 1.13 |
| 2-Sided |
| 90 |
| 0.69 |
| 1.87 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 1.49 | 2-Sided | 90 | 0.90 | 2.44 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 2.49 | 2-Sided | 90 | 1.51 | 4.09 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.94 | 2-Sided | 90 | 0.57 | 1.54 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.54 |
| 2-Sided |
| 90 |
| 0.35 |
| 0.83 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.18 | 2-Sided | 90 | 0.12 | 0.27 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.07 | 2-Sided | 90 | 0.05 | 0.11 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.27 | 2-Sided | 90 | 0.18 | 0.43 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.91 |
| 2-Sided |
| 90 |
| 0.71 |
| 1.17 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.80 | 2-Sided | 90 | 0.62 | 1.03 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 0.76 | 2-Sided | 90 | 0.59 | 0.97 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR | 2.81 | 2-Sided | 90 | 2.16 | 3.65 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.63 |
| 2-Sided |
| 90 |
| 0.45 |
| 0.90 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.67 | 2-Sided | 90 | 0.47 | 0.94 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.60 |
| 2-Sided |
| 90 |
| 0.35 |
| 1.01 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.61 | 2-Sided | 90 | 0.36 | 1.04 | Other | GMR (Renal Impairment/Healthy Control) |
| GMR |
| 0.91 |
| 2-Sided |
| 90 |
| 0.41 |
| 2.00 |
| Other |
GMR (Renal Impairment/Healthy Control) |
| GMR | 0.81 | 2-Sided | 90 | 0.37 | 1.78 | Other | GMR (Renal Impairment/Healthy Control) |
|
| 2 hours postdose |
|
|
| 2.5 hours postdose |
|
|
| 3.0 hours postdose |
|
|
| 3.5 hours postdose |
|
|
| 4 hours postdose |
|
|
| 4.5 hours postdose |
|
|
|
| 2 hours postdose |
|
|
| 2.5 hours postdose |
|
|
| 3.0 hours postdose |
|
|
| 3.5 hours postdose |
|
|
| 4 hours postdose |
|
|
| 4.5 hours postdose |
|
|