imipenem-resistant bacterial infections, including hospital-associated or ventilator acquired pneumonia (HABP/VABP), complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI). MedDRA version: 19.1 Level: LLT Classification code 10071097 Term: Beta-lactam antibiotic resistance System Organ Class: 100000004862
Conditions
Interventions
Product Name: Imipenem/Cilastatin + MK-7655
Product Code: MK-7655A
Pharmaceutical Form: Powder for injection
INN or Proposed INN: IMIPENEM
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for the blinded treatment groups (Treatment Groups 1 and 2) are similar to those for the open-label treatment group (Group 3) with the exceptions as noted. Subjects must be adults (>18 yrs) who require hospitalization and IV treatment for a serious bacterial infection with at least one of 3 eligible primary infection sites (HABP/VABP, cIAI and/or cUTI) and who have a culture collected from the primary infection-site within 1 week of study entry showing that at least one of the suspected causative pathogen(s) from that specimen is Gram-negative, imipenem-resistant, imipenem/MK-7655 susceptible, and colistin susceptible (subjects in treatment group 3 must have colistin-resistant rather than colistin-susceptible pathogens). Subjects must also, if of reproductive potential, agree to avoid becoming pregnant or impregnating a partner from the time of consent through completion of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 78 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Exclusion criteria for the blinded treatment groups (Treatment Groups 1 and 2) are similar to those for the open-label treatment group (Group 3) with the exceptions as noted. The subject must be excluded from the trial if the subject has an APACHE II score >30 at screening;has an infection in which any of the causative pathogens are IMI-R Acinetobacter spp., suspected Class B metallo-beta-lactamase-producing bacteria (including NDM-1, IMP or VIM-containing strains, has a concurrent infection that would interfere with evaluation of response to the study antibiotics such asendocarditis, osteomyelitis, meningitis, prosthetic joint infection, active pulmonary tuberculosis or a disseminated fungal infection. A subject is also excluded if he/she has received treatment with any form of systemic colistin for > 24 hours within the 72 hours immediately prior to initiation of study therapy (Group 1 and 2 only, has HABP/VABP caused by an obstructive process, has cUTI with complete obstruction of any portion of the urinary tract, known ileal loop, intractable vesico-ureteral reflux or presence of indwelling urinary catheter which cannot be removed at study entry. Pregnant females as well as subjects with hypersensitivity to any of the study drug, subjects with seizure disorder, with an estimated or actual creatinine clearance of less than 15 mL/min at screening or is undergoing hemodialysis or peritoneal dialysis will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The timing is dependent on the subject’s primary infection site. For HABP/VABP and cIAI, it is Day 28 post-randomization and for cUTI it is 5 to 9 days following completion of study therapy.; Main Objective: (1) To estimate the proportion of subjects with favorable overall response to IMI/MK-7655 (Treatment Group 1 only) and to CMS + IMI (Treatment Group 2). The overall response will be estimated based on the following: (a) survival (based upon all-cause mortality) through Day 28 post-randomization in subjects with HABP/VABP, (b) clinical response at Day 28 post-randomization for subjects with cIAI and (c) the composite clinical and microbiological response at the early follow-up visit, EFU (Day 5 to 9 following completion of therapy) for subjects with cUTI. (2) To evaluate the safety and tolerability profile of IMI/MK-7655 (Treatment Group 1 only). ;Secondary Objective: (1) To estimate the proportion of subjects with a favorable clinical response to IMI/MK-7655 (Treatment Group 1 only) and CMS + IMI (Treatment Group 2) at Day 28 post-randomization; (2) To estimate the incidence of all-cause mortality through Day 28 post-randomization in Treatment Group 1 (IMI/MK-7655) and in Treatment Group 2 (CMS + IMI); (3) To estimate the proportion of subjects who experience treatment-emergent nephrotoxicity in Treatment Group 1 (IMI/MK-7655) and in Treatment Group 2 (CMS + IMI). Other secondary objective include evaluation of clinical response at various other timepoints during the trial, including on-therapy and post-therapy visits as well as evaluation of microbiological response in subjects with cUTI.; Primary end point(s): The primary efficacy endpoint of the study is overall response. As the efficacy in clinical studies is typically measured differently for different infection types, overall response will be estimated based on the following: (a) al | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): There are two key secondary measurements for efficacy in this study: • Clinical response at 28 days following initiation of IV study therapy (through Day 28 post-randomization) • All-cause mortality within 28 days after initiation of study therapy (through Day 28 post-randomization) Additional secondary endpoints include the following: • Clinical response at various other timepoints during the trial, including at Day 3 of study therapy (OTX), End of study therapy (EOT) and EFU. •Microbiological response in subjects with cUTI will be evaluated at OTX, EOT and at EFU. ;Timepoint(s) of evaluation of this end point: Both key secondary endpoints will be evaluated 28 days following randomization. Evaluation of other secondary endpoints is varied and included on Day 3 of study therapy, at the end of study therapy and 5 to 9 days following the end of study therapy. | — |
Countries
Brazil, Colombia, Estonia, Germany, Greece, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Peru, Romania, South Africa, Turkey, Ukraine, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed