A Phase 3 study to assess efficacy and safety of oral tebipenem compared to IV imipenem-cilastatin in adults with cUTI/AP
- Conditions
- complicated urinary tract infection (cUTI) or acute pyelonephritis (AP)MedDRA version: 20.0Level: PTClassification code: 10046571Term: Urinary tract infection Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- CTIS2023-503785-22-00
- Lead Sponsor
- Spero Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 2648
male and female patients at least 18 years of age, patients enrolled in India must be =90 years of age, able to provide informed consent, able to ingest oral tablets for the anticipated treatment duration. If present at Baseline, nausea and/or vomiting should be mild or well controlled with antiemetic therapy, have a diagnosis of cUTI or AP as defined below: a. cUTI definition: at least TWO of the following signs and symptoms: •chills, rigors, or fever (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F]); fever must be observed and documented by a health care provider •dysuria, urgency to void, or increased urinary frequency •nausea or vomiting, as reported by the patient •lower abdominal pain, suprapubic pain, pelvic pain or flank pain/costovertebral angle tenderness. AND at least ONE of the following risk factors for cUTI: •implanted urinary tract instrumentation (e.g., nephrostomy tube, ureteric stents, or other urinary tract prosthetic material), ongoing intermittent bladder catheterization, or presence of an indwelling bladder catheter (Note: bladder catheters that have been in place for >24 h prior to Screening must be removed or replaced prior to collection of the Screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated) •current known functional or anatomical abnormality of the urogenital tract, including anatomic abnormalities of the urinary tract, neurogenic bladder, or post-void residual urine volume of =100 milliliters (mL) within the past 6 months •complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to EOT visit) •known intrinsic renal disease with blood urea nitrogen (BUN) >20 mg/deciliter (dL), or blood urea >42.8 mg/dL, or serum creatinine (Cr) >1.4 mg/dL •urinary retention, including urinary retention in men due to previously diagnosed benign prostatic hyperplasia (BPH). b. AP definition: acute flank pain (onset within 7 days prior to randomization) or costovertebral angle tenderness on physical examination AND at least ONE of the following signs and symptoms: •chills, rigors, or fever (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F]); fever must be observed and documented by a health care provider •peripheral white blood cell count (WBC) >10,000/cubic millimeter (mm3) or bandemia (>15% immature polymorphonuclear neutrophils [PMNs], regardless of WBC count) •nausea or vomiting, as reported by the patient •dysuria, urgency to void, or increased urinary frequency., have an adequate urine specimen for evaluation and culture obtained within 24 h prior to randomization with evidence of pyuria that includes at least one of the following: •at least 10 WBCs per high power field (HPF) in urine sediment •at least 10 WBCs per mm3 in unspun urine •positive leukocyte esterase (LE) on urinalysis. Note: Patients may be randomized and administered study drug prior to knowledge of urine culture results, but pyuria must be documented, expectation, in the judgment of the Investigator, that the patient will survive with effective antimicrobial therapy and appropriate supportive care for the anticipated duration of the study, willing to comply with all the study activities and procedures throughout the duration of the study, willing to agree to use a highly effective method of birth control; male patients
presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy, including but not limited to the following: •perinephric or renal corticomedullary abscess •uncomplicated urinary tract infection (uUTI [acute cystitis that does not meet the cUTI disease definition; refer to Inclusion Criterion 4.a]) •polycystic kidney disease •recent history of trauma to the pelvis or urinary tract •confirmed or suspected acute or chronic bacterial prostatitis, orchitis, or epididymitis •chronic vesicoureteral reflux •previous or planned renal transplantation •previous or planned cystectomy or ileal loop surgery •known or suspected non-renal source of infection (e.g., infective endocarditis, osteomyelitis, meningitis, pneumonia) •confirmed or suspected infection that is caused by a pathogen that is resistant to either study drug (e.g., carbapenem-resistant pathogen), including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis) or an intrinsically resistant bacterial species not expected to respond to oral IP or comparator IV (e.g., Pseudomonas species), severe hepatic impairment at Screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST)>5×upper limit of normal (ULN) or total bilirubin >3×ULN, or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy), pregnant or lactating women, receipt of any investigational device or investigational medication during the last 30 days or 5 half-lives, whichever is longer, prior to randomization, known history of human immunodeficiency virus (HIV) infection with known CD4 count <200/mm3 or acquired immunodeficiency syndrome (AIDS)-defining illness within the past year, presence of immunodeficiency or an immunocompromised condition including neutropenia (<1,000 neutrophils/mm3 obtained from the local laboratory at Screening), hematologic malignancy, bone marrow transplant, or receiving immunosuppressive therapy such as cancer chemotherapy, medications for the rejection of transplantation, and long-term use of systemic corticosteroids (e.g., =20 mg/day of prednisone or systemic equivalent for at least 2 weeks), QT interval corrected using Fridericia’s formula (QTcF) >480 msec based on screening electrocardiogram (ECG), history of significant hypersensitivity or allergic reaction to ß-lactam antimicrobials (e.g., cephalosporins, penicillins, carbapenems), product excipients (mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and Opadry®) or any contraindication to the use of imipenem-cilastatin, history of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic acidemia), requirement for concomitant use of valproic acid, divalproex sodium, or probenecid between randomization and EOT, unable or unwilling to comply with the protocol, history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures), an employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or the Investigator, history of proven or suspected Clostridioides difficile associated diarrhea, gross hematuria requiring intervention other than administr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method