Infections Caused by Acinetobacter baumannii-calcoaceticus Complex MedDRA version: 20.0 Level: LLT Classification code 10003999 Term: Bacteremia System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: PT Classification code 10037597 Term: Pyelonephritis acute System Organ Class: 10021881 - Infections and infestati
Conditions
Interventions
Product Name: durlobactam
Product Code: durlobactam,ETX2514 Sodium, NaETX2514
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: durlobactam
CAS Number: 1467157-21-6
Current Sp
Sponsors
Entasis Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria for Part A and B: 1.A signed informed consent form (ICF);Note: If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient, or the decision can be made according to the procedure permitted by local law and institutional Standard Operating Procedures; in compliance with the protocol 2. Male or female = 18 years of age; 3. A confirmed diagnosis of a serious infection and the expectation, in the judgment of the Investigator, that the patient's infection will require treatment with intravenous (IV) antibiotics; 4. A known infection caused by ABC (bacteremia, HABP, VABP,VP, cUTI or AP, or surgical or post traumatic wound infections) as either a single pathogen or member of a polymicrobial infection based on evidence from culture or, if available, rapid diagnostic test from a sample collected within 72 hours prior to randomization (HABP/VABP/VP patients), AND 1 of the following: a.Has received no more than 48 hours of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug; OR b. Is clinically failing prior treatment regimens (ie, clinical deterioration or failure to improve after at least 48 hours of antibiotic treatment); 5.APACHE II score between 10 and 30, inclusive, OR SOFA score between 7 and 11, inclusive, at the time of diagnosis of infection. Patients who are not being treated in an intensive care unit and cannot have an APACHE II or SOFA score performed should have a qSOFA score more/equal?2 for enrollment; 6. Expectation, in the judgment of the Investigator, that the patient will benefit from effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study; and Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug; 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 256 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1. Presence of suspected or confirmed deep-seated infection (eg, lung abscess in patients with pneumonia, skin abscess, or decubitus ulcer) that is not planned on being drained or debrided within 24 hours after randomization; 2. Evidence of active concurrent pneumonia requiring additional antimicrobial treatment caused by e.g. Streptococcus pneumoniae, Haemophilus influenzae, etc; 3.Pulmonary disease that precludes evaluation of a therapeutic response (such as lung cancer resulting in bronchial obstruction or on the same side as the pneumonia, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, lung abscess, pleural empyema, or post obstructive pneumonia); 4. Presence of suspected or confirmed deep seated bacterial infections such as bacterial Gram negative osteomyelitis, endocarditis, or meningitis requiring prolonged therapy, as determined by history and/or physical examination; 5.Acute infective endocarditis due to Gram positive bacteria that require urgent/emergent indication of surgery (ie, heart failure because of valvular insufficiency or septic shock), or patients in whom surgery is contraindicated due to prohibitive risk for surgery due to comorbidities; 6. Irremovable implantable device or line thought to be the potential source of ABC infection; 7.Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) above/equal 60 mmHg; 8.For patients to be enrolled with the primary indication of HABP, VABP, or VP, any of the following conditions: a.Diagnosis of ventilator-associated tracheobronchitis; or b.Inability to provide proper respiratory specimens for culture. Respiratory samples from expectorated or induced sputum should show 25 polymorphonuclear neutrophils per 100xfield; 9.For patients to be enrolled with the primary indication of cUTI or AP, any of the following urologic conditions: a.Likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI (eg, patients with vesico-uretal reflux); b.Suspected or confirmed prostatitis; c.Requirement for bladder irrigation with antibiotics or for antibiotics to be administered directly via urinary catheter; d.Previous or planned cystectomy or ileal loop surgery; e.Uncomplicated urinary tract infection (eg, female patients with urinary frequency, urgency, or pain or discomfort without systemic symptoms or signs of infection); f.Complete, permanent obstruction of the urinary tract; g.Suspected or confirmed perinephric or renal corticomedullary abscess; h.Polycystic kidney disease; or i.Any recent history of trauma to the pelvis or urinary tract; 10.Pregnant or breastfeeding women; 11.APACHE II score >30 and SOFA score >11 at the time of diagnosis of infection; 12.Receiving peritoneal dialysis; 13. Requirement for temporary or acute onset treatment with antiseizure medication that, in the opinion of the Investigator, would prohibit the patient from complying with the protocol. Patients at risk of seizure or requiring prophylactic antiseizure medications during the study can be considered for enrollment at the discretion of the Investigator. Patients with a history of epilepsy or who are on stable treatment (ie, no recurrent episodes in the past 30 days) and no history of imipenem-associated seizures may be considered for enrollment in the study; 14.Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or div
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To compare the efficacy of ETX2514SUL plus imipenem/cilastatin to colistin plus imipenem/cilastatin in patients with carbapenem-resistant ABC (CRABC) infections in Part A; •To compare the incidence of nephrotoxicity, as measured by the Risk–Injury–Failure–Loss–End stage renal disease (RIFLE) criteria, of ETX2514SUL to colistin in patients with ABC infections in Part A. ;Secondary Objective: •To compare the efficacy of ETX2514SUL plus imipenem/cilastatin to colistin plus imipenem/cilastatin in all randomized patients in Part A; •To evaluate the efficacy of ETX2514SUL plus imipenem/cilastatin in patients with colistin - or polymyxin B - resistant ABC infections in Part B; •To estimate the efficacy of ETX2514SUL plus imipenem/cilastatin for each primary infection site; •To evaluate and compare the safety of ETX2514SUL and colistin; •To describe the overall safety profile of ETX2514SUL; •To determine the systemic exposure of ETX2514 and sulbactam in a small cohort of severely ill patients administered ETX2514SUL in Part A.;Primary end point(s): 28-day all-cause mortality in the CRABC m-MITT Population in Part A.;Timepoint(s) of evaluation of this end point: Day 5, Day 7, EOT, TOC, and LFU Visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 28 days;Secondary end point(s): •28-day all-cause mortality in the ITT Population; •Mortality in the CRABC m-MITT Population •Clinical cure at TOC in the CRABC m-MITT Population; •Clinical cure at TOC in the m-MITT, Clinical Evaluable (CE), Microbiologic Evaluable (ME), and CRABC ME Populations; •Clinical cure at Day 5, Day 7, EOT, and LFU in the m-MITT, CRABC m MITT, CE, ME, and CRABC ME Populations; •Microbiological favorable assessment at Day 5, Day 7, EOT, TOC, and LFU in the m-MITT, CRABC m-MITT, ME, and CRABC ME Populations; •14-day all-cause mortality in the CRABC m-MITT and m-MITT Populations; •28-day all-cause mortality in the m-MITT and CRABC ME Populations; and •PK exposure of ETX2514 and sulbactam in the PK Population. | — |
Countries
Belarus, Brazil, China, Greece, Hungary, India, Israel, Korea, Democratic People's Republic of, Lithuania, Mexico, Peru, Puerto Rico, Russian Federation, Taiwan, Thailand, Turkey, United States
Contacts
Public ContactClinical Trial Manager
Roberta Carboni
Outcome results
None listed