Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013)

The percentage of participants experiencing AEs that occurred in ≥4 participants within either Group 1 or Group 2 was assessed. 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. Statistical analysis included only Groups 1 and 2 as indicated by the protocol; Group 3 had \<4 participants and therefore no data are presented.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1 and 2 who received ≥1 dose of study drug are included. Group 3 data is not shown for this measure because there are only 3 participants.

The percentage of participants in Group 1, 2, and 3 discontinuing from study drug due to ≥1 AEs during the treatment period was determined. 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. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 21

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 discontinuing from study drug due to ≥1 drug-related AEs during the treatment period was determined. A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 21

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 AEs during treatment and 14-day follow-up was determined. 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. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 drug-related AEs during treatment and 14-day follow-up was determined. A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 drug-related SAEs during treatment and 14-day follow-up was determined. A drug-related SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 having ECIs within 2 categories was determined. Category 1 ECIs included post-baseline laboratory values of an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value that is ≥3x upper limit of normal (ULN) and an elevated total bilirubin value that is ≥2x ULN and (at the same time) an alkaline phosphatase value that is ≤2x ULN. Category 2 ECIs included a confirmed elevated AST or ALT value that is ≥5x ULN. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 SAEs during treatment and 14-day follow-up was determined. An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.

The percentage of participants with FOR was determined for Groups 1 and 2. FOR was determined based on clinically relevant outcomes for the primary site of infection as follows: HABP/VABP: survival through Day 28; cIAI: favorable clinical response (all pretherapy symptoms of index infection resolved with no evidence of resurgence, no additional antibiotic therapy required, and no unplanned surgical or percutaneous drainage procedures) at Day 28; cUTI: favorable composite clinical response (all pretherapy symptoms of index infection resolved with no evidence of resurgence, no additional antibiotic therapy required) and microbiological response (urine culture shows sustained eradication of the baseline uropathogen \[e.g., ≥10\^5 CFU/mL at study entry is reduced to \<10\^4 CFU/mL\]) at Early Follow-up (EFU).

Time frame: Up to Day 30 (up to 9 days after completing study treatment)

Population: Participants in Groups 1 and 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FMR at OTX was determined for participants with cUTI in Groups 1 and 2. FMR was defined as urine culture results at OTX showing eradication (i.e., ≥10\^5 colony forming units \[CFU\]/mL at baseline was reduced to \<10\^4 CFU/mL at OTX) of the uropathogen.

Time frame: OTX (Day 3)

Population: Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FMR at EFU was determined for participants with cUTI in Groups 1 and 2. FMR was defined as urine culture results at EFU showing sustained eradication (i.e., ≥10\^5 CFU/mL at baseline that was reduced to \<10\^4 CFU/mL previously remained \<10\^4 CFU/mL at EFU) of the uropathogen.

Time frame: EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])

Population: Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FMR at EOT was determined for participants with cUTI in Groups 1 and 2. FMR was defined as urine culture results at EOT showing eradication (i.e., ≥10\^5 CFU/mL at baseline was reduced to \<10\^4 CFU/mL at EOT) or sustained eradication (i.e., ≥10\^5 CFU/mL at baseline that was reduced to \<10\^4 CFU/mL previously remained \<10\^4 CFU/mL at EOT) of the uropathogen.

Time frame: At EOT (up to Day 21)

Population: Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

Treatment-emergent nephrotoxity was assessed in Groups 1 and 2 as indicated by the protocol (Group 3 was not included). Nephrotoxicity for participants with normal baseline serum creatinine levels (\<1.2 mg/dL) was defined as doubling of serum creatinine to \>1.2 mg/dL or reduction in creatinine clearance (ClCR) of ≥50%. Nephrotoxicity for participants with pre-existing renal dysfunction (baseline serum creatinine level ≥1.2 mg/dL) was defined as increase in serum creatinine by ≥1 mg/dL or reduction from baseline ClCR of ≥20% or need for renal replacement therapy (RRT).

Time frame: Up to Day 35 (up to 14 days after completing study treatment)

Population: All participants in Groups 1 and 2 who received ≥1 dose of study drug are included. Per protocol, Group 3 was not included in the nephrotoxicity analysis.

The percentage of participants with all-cause mortality up to Day 28 was determined for Groups 1 and 2.

Time frame: Up to Day 28

Population: Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FCR at Day 28 was determined for Groups 1 and 2. FCR at Day 28 was defined as sustained cure or cure. Sustained cure (for participants with cure response at the prior visit) was defined as all pretherapy signs and symptoms of index infection resolved with no evidence of resurgence and no additional antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed. Cure (for participants with improved response at EOT visit) was defined as all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed.

Time frame: Day 28

Population: Participants in Groups 1 and 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FCR at EFU was determined for Groups 1 and 2. FCR at EFU was defined as sustained cure or cure. Sustained cure (for participants with cure response at the prior visit) was defined as all pretherapy signs and symptoms of index infection resolved with no evidence of resurgence and no additional antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed. Cure (for participants with improved response at EOT visit) was defined as all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed.

Time frame: EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])

Population: Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with FCR at EOT was determined for Groups 1 and 2. FCR at EOT was defined as cure or improved. Cure was defined as all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed. Improved was defined as all or most pretherapy signs and symptoms of index infection have improved or resolved, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed.

Time frame: At EOT (up to Day 21)

Population: Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.

The percentage of participants with a FCR at OTX was determined for Groups 1 and 2. FCR at OTX was defined as improved. Improved was defined as all or most pretherapy signs and symptoms of index infection have improved or resolved, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed.

Time frame: OTX (Day 3)

Population: Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.