A Trial of HRS-8427 in the Treatment of Adults With Complicated Urinary Tract Infection, Including Acute Pyelonephritis

Inclusion criteria

• Able and willing to provide a written informed consent before the study, fully understand the study and be able to complete the study according to the protocol;
• Male and female, ≥18 years;
• Judged by the investigator, clinical diagnosis with cUTI or AP, expectation that the patients will require hospitalization and initial treatment with intravenous antibiotics;
• Urine specimen with evidence of pyuria；
• Have urine culture specimen obtained within 48 hours prior to randomization;
• 48 hours before random, allowing a short course of antimicrobial drug treatment is less than 24 hours (random rate ≤25%)
• Women of childbearing potential must have a negative serum pregnancy test before first dose, must be non-lactating. Fertile female subjects or male subjects whose partner is a fertile female agree to use highly effective form of contraception, with no plan of birth, sperm/ovum donation from the time of signed ICF till 14 days after end of treatment.

Exclusion criteria

• History of significant hypersensitivity or allergic reaction to any β-lactam, or any β-lactamase inhibitors;
• Known history of immune deficiency disease or receive immunocompromising treatment;
• Severe cardiovascular and cerebrovascular diseases with clinical significance and unstable condition or uncontrolled;
• Known or suspected central nervous system disorder or other factors that may predispose to seizures or lower the seizures onset threshold;
• Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy;
• Uncomplicated lower urinary tract infection;
• Suspected or confirmed urinary tract symptoms caused by acute/chronic prostatitis, orchitis, epididymitis or sexually transmitted diseases as determined by medical history and/or physical examination;
• Patients received cancer treatment within 4 weeks before randomization or planned treatment during the study period;
• Systemic antimicrobial therapy other than the investigational drug need to be used during the study period, with the exception of topical or single oral dose of antifungal treatment
• Urinary tract surgery prior to 7 days before randomization or surgery planned during the study period;
• Indwelling catheter or urinary apparatus, the researchers determine drug treatment period cannot be removed;
• Receipt of potentially effective systemic antibacterial therapy for a continuous duration of ≥24 hours during the previous 48 hours prior to the randomization;
• History of pelvis or urinary tract trauma prior to the randomization;
• Patients had severe trauma or received major surgery prior to the randomization;
• Impairment of renal function with estimated glomerular filtration rate or Creatinine Clearance <15 mL/min ;
• Laboratory abnormalities in baseline specimens obtained at screening;
• A QTcF interval prolongation at screening or abnormalities with clinical significance and may cause obvious safety risk to the subjects;
• Known urine culture with at least one Gram-Negative uropathogen at ≥105 colony-forming units(CFU)/mL unsusceptible to Imipenem and Cilastatin Sodium, or only identify Gram-positive uropathogen, or confirmed fungal urinary tract infection with ≥103CFU/mL;
• Likely to require the use of antibiotic drug prevention after treatment;
• Suspected of sepsis, producing life-threatening organ dysfunction;
• Estimated survival within 6 weeks or rapidly progressive or end stage disease with high mortality rate;
• Drug abuse prior to the randomization;
• Participated in a previous clinical study related to HRS-8427 and used HRS-8427 or have participated in another clinical study within 4 weeks before randomization and used a study drug containing the active ingredient;
• Judgment of the Investigator, other reasons unsuitable for study.