Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
IMI/REL · 3 trials · 3 indications
For each participant, survival status was assessed at Day 28 post-randomization and recorded on the electronic Case Report Form. The percentage of participants with all-cause mortality through Day 28 in the MITT population is presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs are presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE are presented.
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma imipenem (IMI) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration.
Central volume of distribution (Vc) of plasma IMI was calculated.
Systemic clearance (CL) of plasma IMI was calculated.
Percentage of time spent above the minimum inhibitory concentration (%TMIC) of plasma IMI was calculated. %TMIC is defined as the percentage of time (in hours) in which the lowest concentration of a study drug, completely inhibits growth of the specific organism being tested.
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma relebactam (REL) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration.
Systemic clearance (CL) of plasma REL was calculated.
Central volume of distribution (Vc) of plasma REL was calculated.
Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma cilastatin (CIL) was not calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
Time to maximum plasma concentration (Tmax) of CIL was determined. Tmax is defined as the time after drug administration at which peak drug concentration in plasma occurs.
Concentration at end of infusion (Ceoi) of plasma CIL was determined.
Terminal half-life (t1/2) of plasma CIL was not calculated.
Systemic clearance (CL) of plasma CIL was not calculated.
Volume of distribution (Vss) of plasma CIL was not calculated.
| Arm | Type | Description |
|---|---|---|
| IMI/REL FDC | EXPERIMENTAL | Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL, once every 6 hours for a minimum 7 days, up to 14 days. At the start of IMI/REL treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| PIP/TAZ FDC | ACTIVE_COMPARATOR | Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total. |
| IMI/REL | EXPERIMENTAL | Participants with cIAI or cUTI will receive imipenem/cilastatin/relebactam (IMI/REL) via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive IMI/REL via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive IMI/REL via IV infusion for 14 days. All oral switch medications will be chosen from a list of acceptable approved agents and will be administered per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. |
| Active Control | ACTIVE_COMPARATOR | Participants with cIAI or cUTI will receive active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive active control via IV infusion for 14 days. All active control and oral switch medications will be administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications will be chosen from a list of acceptable approved agents. |
| Name | Type | Description |
|---|---|---|
| IMI/REL FDC | DRUG | 500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial |
| PIP/TAZ FDC | DRUG | 4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial |
| Linezolid | DRUG | Open-label 600 mg Linezolid |
| IMI/REL | DRUG | Age-based dosing: * 12 to \<18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours * 6 to \<12 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 2 to \<6 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 3 months to \<2 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * Birth to \<3 months, IMI 15 and REL 7.5 mg/kg, IV infusion every 8 hours NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. |
| Active Control | DRUG | All active control medications will be chosen from a list of acceptable approved agents for each infection type (HABP or VABP, cIAI, and UTI) and will be given via IV infusion, per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. All oral switch medications will be chosen from a list of acceptable approved agents. |
| Oral Switch | DRUG | All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. |
Inclusion Criteria: * Requires treatment with IV antibiotic therapy for HABP or VABP * Fulfills clinical and radiographic criteria within 48 hours prior to randomization, with onset of criteria occurring after more than 2 days of hospitalization or within 7 days after discharge from a hospital for ...
IMI/REL is used for hospital-acquired bacterial pneumonia and suspected or documented gram-negative bacterial infections. It is an investigational small molecule being developed by Merck & Company, Inc. (MRK) for infectious disease. The drug is currently in Phase 3 clinical development.
IMI/REL is a combination antibiotic that targets gram-negative bacteria. It contains imipenem, cilastatin, and relebactam. The drug is designed to treat infections caused by susceptible gram-negative pathogens, including those resistant to other antibiotics.
IMI/REL is being developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is conducting clinical trials to evaluate the drug for hospital-acquired bacterial pneumonia and gram-negative bacterial infections.
IMI/REL is in Phase 3 clinical development. The drug is investigational and not yet approved. A Phase 3 trial comparing IMI/REL to piperacillin/tazobactam in patients with hospital-acquired or ventilator-associated bacterial pneumonia has been completed.
IMI/REL has been studied in two completed trials. NCT03583333 is a Phase 3 trial in hospital-acquired or ventilator-associated bacterial pneumonia. NCT03230916 and NCT03969901 are pediatric trials in gram-negative infections, with the latter being Phase 2.
Yes, IMI/REL is also known as MK-7655A. Clinical trials for the drug use the MK-7655A designation, such as NCT03583333, which evaluates imipenem/cilastatin/relebactam (MK-7655A) versus piperacillin/tazobactam.