Multicenter study to assess the efficacy, safety and pharmacokinetics of the study drug tebipenem pivoxil hydrobromide compared with ertapenem in complicated urinary tract infections.
- Conditions
- complicated urinary tract infection or acute pyelonephritisMedDRA version: 20.0Level: PTClassification code 10046571Term: Urinary tract infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2018-003671-35-EE
- Lead Sponsor
- Spero Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1. Male and female subjects at least 18 years of age
2. Able to provide informed consent
3. 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, in order to tolerate oral study drug.
4. Have a diagnosis of cUTI or AP as defined below:
a. cUTI definition:
At least TWO of the following signs and symptoms:
i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C)
ii. Dysuria, urgency to void, or increased urinary frequency
iii. Nausea or vomiting, as reported by the subject
iv. Lower abdominal, suprapubic, or pelvic pain
AND at least ONE of the following risk factors for cUTI:
i. 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 hours 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)
ii. 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 milliliter (mL) within the past 6 months
iii. 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 End-of-Treatment [EOT])
iv. Known intrinsic renal disease with blood urea nitrogen (BUN) >20 mg/deciliter (dL), or blood urea >42.8 mg/dL, or serum creatinine >1.4 mg/dL
v. 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:
i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C)
ii. Peripheral white blood cell count (WBC) >10,000/mm3 or bandemia (> 15% immature polymorphonuclear neutrophils [PMNs], regardless of WBC count)
iii. Nausea or vomiting, as reported by the subject
iv. Dysuria, urgency to void, or increased urinary frequency
Note: Subjects who meet the definition for cUTI (Inclusion Criterion 4a) and also have flank pain or costovertebral tenderness should be randomized as cUTI rather than AP.
5. Have an adequate urine specimen for evaluation and culture obtained within 24 hours prior to randomization with evidence of pyuria that includes at least one of the following:
a. At least 10 WBCs per high power field (hpf) in urine sediment
b. At least 10 WBCs per cubic millimeter (mm3) in unspun urine
c. Positive leukocyte esterase (LE) on urinalysis
Note: Subjects may be randomized and administered IP prior to knowledge of urine culture results.
6. Expectation, in the judgment of the Investigator, that the subject will survive with effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study
7. Willing to comply with all the study activities and procedures throughout the duration
1. 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:
a. Perinephric or renal corticomedullary abscess
b. Uncomplicated urinary tract infection (uUTI [acute cystitis that does not meet the cUTI disease definition, see Inclusion Criterion 4a])
c. Polycystic kidney disease
d. Recent history of trauma to the pelvis or urinary tract
e. Confirmed or suspected acute or chronic bacterial prostatitis, orchitis, or epididymitis
f. Chronic vesicoureteral reflux
g. Previous or planned renal transplantation
h. Previous or planned cystectomy or ileal loop surgery
i. Known or suspected non-renal source of infection (e.g., infective endocarditis, osteomyelitis, meningitis, pneumonia)
j. Confirmed or suspected infection that is caused by a pathogen that is resistant to either IP (e.g., carbapenem-resistant pathogen), including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis)
2. Gross hematuria requiring intervention other than administration of IP or removal/placement of urinary tract instrumentation
3. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required relieving an obstruction or placing urinary tract instrumentation)
4. Creatinine clearance (CrCl) of <30 mL/min, as estimated by the Cockcroft-Gault formula:
eCCr[mL/min]=(140-Age [yrs]) × Body Weight [kg] × [0.85 if Female]/72 × Serum Creatinine [mgdL/]
5. Anticipated concomitant use of non-study antibacterial drug therapy between randomization and the LFU Visit that would potentially effect outcome evaluations of cUTI/ AP, including but not limited to antibacterials with potential activity versus uropathogens, antibacterial drug prophylaxis, and antibacterial bladder irrigation
6. Anticipated concomitant use of gastric acid-reducing medications between randomization and EOT, including proton pump inhibitors, histamine-2 receptor antagonists and antacids
7. Receipt of more than a single dose of a short-acting potentially effective antibiotic started within 72 h prior to randomization (see Appendix 2 for allowed single dose, short-acting antibiotics)
8. Severe hepatic impairment at Screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x upper limit of normal (ULN) or total bilirubin >3x ULN, or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy)
9. Any signs of severe sepsis, including shock or profound hypotension defined as systolic blood pressure <90 mmHg or a decrease of >40 mmHg from baseline that is not responsive to fluid challenge
10. Pregnant or breastfeeding women
11. History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures)
12. Receipt of any investigational medication during the last 30 days or 5 half-lives, whichever is longer, prior to randomization
13. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-defining illness, or known CD4 count <200/mm3 within the past year
14. 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, medic
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