Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Relebactam
MK-7655 · 3 trials · 4 indications
A favorable clinical response was assessed by the clinical investigator as a cure, and was defined as a situation where all or most pre-therapy signs and symptoms of the index infection had resolved, or returned to pre-infection status, and no additional antibiotic therapy was required.
Pre-specified events of interest were confirmed (i.e., verified by repeat testing) elevated AST or ALT laboratory value that is greater than or equal to 5 X ULN as a result of within-protocol-specific testing or unscheduled testing.
Pre-specified events of interest were a confirmed (i.e., verified by repeat testing) elevated AST or ALT laboratory value that is greater than or equal to 3X ULN, as well as elevated total bilirubin greater than or equal to 2X the ULN, and alkaline phosphatase values that are less than 2X the ULN, as a result of within-protocol-specific testing or unscheduled testing.
An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE.
A serious adverse event (SAE) is any AE occurring at any dose that is life threatening; results in a persistent or significant disability/incapacity; prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; or results in death.
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. A drug-related AE is a AE determined by the investigator to be possibly, probably or definitely related to drug treatment.
A SAE is any AE occurring at any dose that is life threatening; results in a persistent or significant disability/incapacity; prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; or results in death. A drug-related SAE is a SAE determined by the investigator to be possibly, probably or definitely related to drug treatment.
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. AEs assessed by the investigator that caused discontinuation of participant treatment are presented.
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. A drug-related AE is an AE determined by the investigator to be possibly, probably or definitely related to drug treatment. Drug-related AEs assessed by the investigator that caused discontinuation of participant treatment are presented.
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. AE preferred terms, with incidence greater than or equal to 4 in one treatment group are presented. AEs preferred terms which did not achieve this threshold are not reported. AE preferred terms are based on MedDRA version 17.0.
Predefined limit of change (PDLC) are presented based on values from the following laboratory tests on serum: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Bil), and alkaline phosphatase (AP). Results are presented for PDLC from tests with reported incidence greater than or equal to 4 participants in one treatment group. Laboratory tests which did not achieve the PDLC threshold are not reported.
A system organ class (SOC) is the highest level of terminology used to describe disorders of the human body, and distinguishes by either anatomical or physiological systems, disease origin or purpose. SOCs with AE incidence greater than or equal to 4 in one treatment group are presented. SOCs with AE incidence which did not achieve this threshold are not reported. SOCs are based on MedDRA version 17.0.
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of \< 2X ULN were recorded.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
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.
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\[100\*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration\].
| Arm | Type | Description |
|---|---|---|
| Relebactam 250 mg with imipenem/cilastatin | EXPERIMENTAL | Participants randomized to receive relebactam 250 mg will be administered 250 mg doses of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval. A 500 mg dose of imipenem/cilastatin will be administered in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
| Relebactam 125 mg with imipenem/cilastatin | EXPERIMENTAL | Participants randomized to receive relebactam 125 mg will be administered 125 mg doses of relebactam IV, in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval. A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
| Placebo to relebactam with imipenem/cilastatin | PLACEBO_COMPARATOR | Participants randomized to receive placebo for relebactam will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours. A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
| Relebactam placebo with imipenem/cilastatin | PLACEBO_COMPARATOR | Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Relebactam 250 mg | DRUG | Relebactam 250 mg IV every 6 hours for a minimum of 96 hours |
| Relebactam 125 mg | DRUG | Relebactam 125 mg IV every 6 hours for a minimum of 96 hours |
| Imipenem/cilastatin | DRUG | A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
| Matching placebo to relebactam | DRUG | Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours. |
| imipenem/cilastatin 500 mg | DRUG | A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
| Placebo to relebactam | DRUG | Participants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours. |
| Ciprofloxacin | DRUG | After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily |
| MK-7655 | DRUG | 125 mg intravenous (IV) over 30 minutes as a single dose |
| 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 |
Inclusion Criteria: * Clinically suspected and/or bacteriologically documented cIAI requiring hospitalization and treatment with IV antibiotic therapy. * Enrolled intraoperatively or postoperatively on the basis of operative findings OR enrolled preoperatively on the basis of compelling preoperativ...
MK-7655, also known as relebactam, is an investigational small-molecule antibacterial agent developed by Merck & Company, Inc. (MRK). It is being studied in infectious disease, specifically for complicated intra-abdominal infections and complicated urinary tract infections, and is given in combination with imipenem/cilastatin in clinical trials.
MK-7655 is being studied for the treatment of serious bacterial infections, including complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis. In trials it is administered together with imipenem/cilastatin and compared with imipenem/cilastatin alone. It is investigational and has not been approved for these uses.
MK-7655 is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck sponsored the clinical program evaluating relebactam in combination with imipenem/cilastatin for complicated intra-abdominal infections and complicated urinary tract infections.
MK-7655 is in clinical development. The program includes Phase 1 and Phase 2 studies, and the drug is investigational rather than approved. A single-dose Phase 1 pharmacokinetic study was conducted in participants with impaired renal function, and Phase 2 trials evaluated the combination in complicated intra-abdominal and urinary tract infections.
MK-7655 has been studied in completed trials including NCT01506271, a Phase 2 trial of relebactam plus imipenem/cilastatin versus imipenem/cilastatin alone in complicated intra-abdominal infection with 351 participants, and NCT01505634, a Phase 2 trial in complicated urinary tract infection with 302 participants. NCT01275170 was a Phase 1 pharmacokinetic study in impaired renal function.
Yes, MK-7655 is the same compound as relebactam. Relebactam is the international nonproprietary name, and MK-7655 is Merck's internal development code for the same small-molecule agent. References to relebactam 250 mg describe the same drug candidate studied in combination with imipenem/cilastatin.