Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Colistimethate · 1 trial · 1 indication
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).
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Group 1: Imipenem+Cilastatin/Relebactam | EXPERIMENTAL | Participants will be stratified by infection type (HABP/VABP, cIAI, and cUTI) and randomized to receive imipenem+cilastatin/relebactam intravenous (IV) infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days for cIAI and cUTI or for 7 to 21 days for HABP or VABP. Treatment durations \>21 days may be approved by the Sponsor for participants requiring longer treatment duration. |
| Group 2: Colistimethate sodium + Imipenem+Cilastatin | ACTIVE_COMPARATOR | Participants will be stratified by infection type (HABP/VABP, cIAI, and cUTI) and randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days for cIAI and cUTI or for 7 to 21 days for HABP or VABP. Treatment durations \>21 days may be approved by the Sponsor for participants requiring longer treatment duration. |
| Group 3: Imipenem+Cilastatin/Relebactam | EXPERIMENTAL | Participants with documented imipenem-resistant and colistin-resistant bacterial infections may be eligible to receive open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days for cIAI and cUTI or for 7 to 21 days for HABP or VABP. Treatment durations \>21 days may be approved by the Sponsor for participants requiring longer treatment duration. |
| Name | Type | Description |
|---|---|---|
| Imipenem+Cilastatin/Relebactam | DRUG | Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, IV infusion once every 6 hours |
| Colistimethate sodium (CMS) | DRUG | Colistimethate base activity 300 mg (\~720 mg CMS) IV infusion loading dose, followed by colistimethate base activity 75 mg to 150 mg (\~180 to 360 mg CMS), depending on renal function, once every 12 hours |
| Imipenem+Cilastatin | DRUG | Imipenem+cilastatin 200 mg to 500 mg, depending on renal function, IV infusion once every 6 hours |
| Placebo to CMS | DRUG | Placebo to CMS IV infusion once every 12 hours |
Inclusion Criteria: * Hospitalization that requires treatment with IV antibiotic therapy for a new, persistent or progressing bacterial infection involving at least 1 of 3 primary infection types (HABP, VABP, cIAI, or cUTI) * Positive culture data from the primary infection-site specimen collected ...
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Colistimethate is a small molecule drug being studied for the treatment of bacterial infections. It is currently in Phase 3 clinical development as an active comparator in a trial for imipenem-resistant bacterial infections. The drug is being developed by Merck & Company, Inc. (MRK).
Colistimethate is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The drug is currently in Phase 3 clinical development for bacterial infections, specifically as a comparator in a study of imipenem-resistant infections.
Colistimethate is in Phase 3 clinical development. It is being studied as an active comparator in a completed Phase 3 trial for bacterial infections. The drug is investigational and has not been approved for use.
Colistimethate was studied in one completed Phase 3 clinical trial, NCT02452047, which evaluated the efficacy and safety of imipenem+cicastatin/relebactam versus colistimethate sodium plus imipenem+cicastatin in imipenem-resistant bacterial infections. The trial enrolled 50 participants.
Colistimethate is a form of colistin, an antibiotic used to treat bacterial infections. In the clinical trial NCT02452047, it is referred to as colistimethate sodium and is used as a comparator against imipenem+cicastatin/relebactam for imipenem-resistant infections.