Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Relebactam · 3 trials · 4 indications
The percentage of participants in the MITT population with mortality due to any cause from randomization through Day 28 was determined for each arm.
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.
| Arm | Type | Description |
|---|---|---|
| IMI/REL | EXPERIMENTAL | Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days. |
| PIP/TAZ | ACTIVE_COMPARATOR | Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Imipenem | DRUG | Imipenem 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days |
| Relebactam | DRUG | Relebactam 250 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days |
| Cilastatin | DRUG | Cilastatin 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days |
| Piperacillin | DRUG | Piperacillin 4000 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days |
| Tazobactam | DRUG | Tazobactam 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days |
| Linezolid | DRUG | Linezolid 600 mg administered open-label by IV every 12 hours for up to 14 days |
| 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 |
Inclusion Criteria: * Requires treatment with IV antibiotic therapy for hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) * Fulfills clinical and radiographic criteria, with onset of criteria occurring after more than 48 hours of hospitalization or wit...
MK-7655, also known as relebactam, is an investigational small molecule being developed for infectious diseases, including complicated intra-abdominal infections, complicated urinary tract infections, and bacterial pneumonia. It is studied in combination with imipenem/cilastatin for these indications.
MK-7655 is a beta-lactamase inhibitor that targets bacterial resistance mechanisms. It is combined with imipenem/cilastatin to restore the activity of imipenem against resistant bacteria. The drug is designed to treat infections caused by bacteria that produce beta-lactamase enzymes.
MK-7655 is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK on the New York Stock Exchange. The company is conducting clinical trials to evaluate the drug for various infectious disease indications.
MK-7655 has completed Phase 1, Phase 2, and Phase 3 clinical trials. The most advanced trial was a Phase 3 study in bacterial pneumonia, which has been completed. The drug is investigational and not yet approved by regulatory authorities.
MK-7655 has been studied in several completed trials, including NCT01275170 (Phase 1, renal impairment), NCT01505634 (Phase 2, complicated urinary tract infection), NCT01506271 (Phase 2, complicated intra-abdominal infection), and NCT02493764 (Phase 3, bacterial pneumonia).
Yes, MK-7655 is also known as relebactam. In clinical trials, it is often referred to as relebactam, particularly in combination with imipenem/cilastatin. The drug is being developed by Merck for treating serious bacterial infections.