Health Condition 1: - Health Condition 2: A488- Other specified bacterial diseases
Conditions
Interventions
Intervention1: Cefepime/Enmetazobactam, 2 g cefepime + 500 mg Enmetazobactam: Dose: For cUTI, including pyelonephritis: 2 gm/500 mg cefepime/enmetazobactam For HAP, including VAP: 2 gm/500 mg cefepime
Sponsors
Orchid Pharma Limited
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Adult male or female patients more than and equal to 18 or less than and equal to 75 years of age 2. Patients who will be able to sign the informed consent voluntarily prior to any study-specific procedures. 3. Subject diagnosed with cUTI including AP and/or HAP including VAP and/or bacteremia associated with these conditions will require hospitalization and initial treatment with at least 7 days of intravenous (IV) antibiotics. 4. Subjects with suspected infection with ESBL-producing organisms susceptible to Cefepime+Enmetazobactam (for patients clinically suspected with Gram-negative infections, perform both Rapid test and standard culture test to confirm ESBL status). 5. Female subjects of childbearing potential must have a negative urine pregnancy test within 1 day prior to study entry. 6. Male and female subjects of childbearing potential must agree to use highly effective contraception methods to avoid pregnancy during the study period. 7. Subjects shall receive a test dose of the study drug, and only those who do not exhibit hypersensitivity shall proceed with the treatment Meet the following clinical criteria for complicated urinary tract infection including acute pyelonephritis: Have at least two of the following new-onset or worsening symptoms or signs: Fever, defined as oral temperature greater than or equal to thirty-eight degrees Celsius (greater than or equal to one hundred point four degrees Fahrenheit), observed and documented by a health care provider within twenty-four hours of Screening; Nausea or vomiting within twenty-four hours of Screening reported by the patient; Dysuria, increased urinary frequency, or urinary urgency; Lower abdominal, suprapubic, or pelvic pain; Evidence of pyuria within forty-eight hours prior to enrolment. Have at least one of the following complicating factors for complicated urinary tract infection: Documented history of urinary retention in male patients (for example, benign prostatic hypertrophy); Use of intermittent bladder catheterization or presence of an indwelling bladder catheter; Azotemia, defined as blood urea nitrogen greater than twenty milligrams per deciliter, blood urea greater than forty-two point eight milligrams per deciliter, or serum creatinine greater than one point four milligrams per deciliter, due to known prior intrinsic renal disease; Any functional or anatomical abnormality of the urogenital tract with voiding disturbance resulting in at least one hundred milliliters of residual urine; Current obstructive uropathy that is scheduled to be medically or surgically relieved during intravenous study therapy and before end of treatment. Have the following criteria for acute pyelonephritis: Acute flank pain (onset within seven days prior to randomization) or costovertebral angle tenderness on physical examination; Dysuria, increased urinary frequency, or urinary urgency; Fever, defined as oral temperature greater than or equal to thirty-eight degrees Celsius (greater than or equal to one hundred point four degrees Fahrenheit), observed and documented by a health care provider within twenty-four hours of Screening; Nausea or vomiting within twenty-four hours of Screening reported by the patient; Evidence of pyuria within forty-eight
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patients meeting any of the following criteria will be excluded from the study: Patients with known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy. Receipt of potentially effective systemic antibacterial therapy for a continuous duration of more than twenty-four hours during the previous seventy-two hours before the study-qualifying baseline urine is obtained. Exceptions: a. Receipt of up to twenty-four hours of a short-acting antibacterial agent (not more than twenty-five percent of subjects who meet this criterion will be enrolled). b. Subjects who received prior antimicrobial therapy for the current complicated urinary tract infection (cUTI) and/or acute pyelonephritis (AP) and: In the Investigator s opinion, failed that prior antibiotic therapy (that is, presented with worsening signs and symptoms); and Documented to have cUTI caused by a pathogen that is non-susceptible to the prior antibiotic therapy; and The causative pathogen is likely to be susceptible to the study drug. c. Subjects who received antibacterial drugs for surgical prophylaxis and subsequently developed cUTI and/or AP. d. Subjects who have received antimicrobial prophylaxis for recurrent cUTI and/or AP and then presented with signs and symptoms consistent with an active new cUTI and/or AP. e. Subjects with culture resistant to Cefepime plus Enmetazobactam. Subjects with rapidly progressive or terminal illness with a high risk of mortality due to any cause, including but not limited to acute hepatic failure, respiratory failure, cardiovascular disease, or septic shock, such that the subject is unlikely to survive the study period. History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any excipients used in the respective formulations, any beta-lactam antibiotics (for example, cephalosporins, penicillins, carbapenems, or monobactams), or any beta-lactamase inhibitors (for example, tazobactam, sulbactam, or clavulanic acid). Pulmonary disease that, in the Investigator s judgment, would preclude evaluation of therapeutic response (for example, lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, or recent pulmonary embolism). Subjects with lung abscess, pleural empyema, or post-obstructive pneumonia. Abnormal liver function test results including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin level greater than three times the upper limit of normal, or presence of liver cirrhosis. Impairment of renal function with estimated glomerular filtration rate (eGFR) less than thirty millilitres per minute per 1.73 square metres, calculated by the four-variable Modification of Diet in Renal Disease (MDRD) equation. Abnormal laboratory findings including platelet count less than fifty thousand per microlitre, absolute neutrophil count less than one thousand per cubic millimetre, or haemoglobin less than eight grams per decilitre. Urinary tract surgery within seven days prior to enrolment or urinary tract surgery planned during the study period. Pneumonia known or suspected to be cause
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of AEs and SAEs, vital signs, laboratory tests, electrocardiogram (ECGs), and physical examinationsTimepoint: Day 1 to Day 14, EOT, TOC, and LFU/ET | — |
Secondary
| Measure | Time frame |
|---|---|
| cUTI including AP 1.To evaluate proportion of subjects with clinical outcome of cure or improvement at EOT, TOC and LFUin terms of clinical cure. 2.To evaluate proportion of subjects with microbiological outcomes at EOT, TOC and LFU in Micro-modified intent to treat (mMITT)populations with a microbiological outcome of Eradication. HAP including VAP 1.To evaluate proportion of subjects with clinical outcome of cure or improvement at EOT, TOC and LFU in terms of clinical cure. 2.To evaluate proportion of subjects with microbiological outcomes at EOT, TOC and LFU in Micro-Modified intent to treat (mMITT) populations with a microbiological outcome of Eradication. Bacteremia associated with cUTI including AP and/or HAP including VAP 1.To evaluate proportion of subjects with absence of bacteremia at EOT, TOC and LFU Timepoint: Day 3, & Day 7/14 EOT, TOC, and LFU/ET. | — |
Countries
India
Contacts
Public ContactDr Manish Rajak
Orchid Pharma Limited
Outcome results
None listed