Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

Completed · Phase 3

Conditions studied: Complicated Urinary Tract Infection, Acute Pyelonephritis

In brief

The key purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of tebipenem pivoxil hydrobromide (TBPM-PI-HBr) compared to intravenous (IV) ertapenem, in participants with complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP).

Key facts

Study ID

NCT03788967

Run by

Spero Therapeutics

People needed

1372

Starts

2019-06-03

Expected to finish

2020-05-27

Last updated by the study team

2022-07-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male and female participants at least 18 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 have been mild or well-controlled with antiemetic therapy, in order to tolerate oral study drug.
• 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 [>100.4°F])
• ii. Dysuria, urgency to void, or increased urinary frequency
• iii. Nausea or vomiting, as reported by the participants
• 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 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 the 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 (Cr) >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 [>100.4°F]).
• 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 participants.
• iv. Dysuria, urgency to void, or increased urinary frequency.
• Note: Participants 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.
• 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.

You may not qualify if…

• Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may have confounded the assessment of efficacy, including but not limited to the following:
• Perinephric or renal corticomedullary abscess.
• Uncomplicated urinary tract infection (cUTI) - (acute cystitis that does not meet the cUTI disease definition, see Inclusion Criterion 4a).
• 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 IP (e.g., carbapenem-resistant pathogen), including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis).
• Gross hematuria requiring intervention other than administration of IP or removal/placement of urinary tract instrumentation.
• 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).
• Creatinine clearance (CrCl) of ≤30 mL/min, as estimated by the Cockcroft-Gault formula:
• estimated Creatinine Clearance (eC_Cr) [mL/min]=((140-Age [yrs]) × Body Weight [kg] × [0.85 if Female])/(72 × Serum Creatinine [mg⁄dL]).
• 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.
• Anticipated concomitant use of gastric acid-reducing medications between randomization and end-of-treatment (EOT), including proton pump inhibitors, histamine-2 receptor antagonists, and antacids.
• Receipt of more than a single dose of a short-acting potentially effective antibiotic started within 72 h prior to randomization.
• Exception: Participants who received more than a single dose of short-acting potentially effective antibiotic within 72 h prior to randomization may be eligible for enrollment if they meet all of the following criteria:
• In the opinion of the Investigator they have failed the prior antibiotic therapy (e.g., have worsening signs and symptoms of cUTI/AP).
• Had a documented uropathogen (growth in urine culture >10\^5 CFU/mL) that is resistant to the prior antibiotic therapy.
• Had a documented uropathogen that is carbapenem-susceptible.
• Received approval from the Medical Monitor to enroll the participants.
• 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).
• 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.

Where it is running

• Medical Facility — Miami, Florida, United States
• Medical Facility — Blagoevgrad, Bulgaria
• Medical Facility — Dobrich, Bulgaria
• Medical Facility — Rousse, Bulgaria
• Medical Facility — Shumen, Bulgaria
• Medical Facility — Sofia, Bulgaria
• Medical Facility — Sofia, Bulgaria
• Medical Facility — Veliko Tarnovo, Bulgaria
• Medical Facility — Karlovy Vary, Czechia
• Medical Facility — Liberec, Czechia
• Medical Facility — Prague, Czechia
• Medical Facility — Ústí nad Labem, Czechia
• Medical Facility — Zlín, Czechia
• Medical Facility — Kohtla-Järve, Estonia
• Medical Facility — Tallinn, Estonia
• Medical Facility — Võru, Estonia
• Medical Facility — Tbilisi, Georgia
• Medical Facility — Tbilisi, Georgia
• Medical Facility — Tbilisi, Georgia
• Medical Facility — Tbilisi, Georgia
• Medical Facility — Zestaponi, Georgia
• Medical Facility — Budapest, Hungary
• Medical Facility — Budapest, Hungary
• Medical Facility — Nagykanizsa, Hungary
• Medical Facility — La Mesa, California, United States

Full record on ClinicalTrials.gov

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