Abstract
Background
Management of complicated urinary tract infections (cUTIs) is increasingly difficult due to rising antimicrobial resistance. There is an unmet need for oral treatment options for antimicrobial-resistant cUTIs. Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an investigational oral carbapenem with activity against antimicrobial-resistant Enterobacterales, including extended-spectrum β-lactamase–positive (ESBL+) pathogens.
Methods
PIVOT-PO (NCT06059846) was a global, randomized, double-blind, non-inferiority (10% margin) Phase 3 study comparing the efficacy and safety of oral TBP-PI-HBr with intravenous (IV) imipenem-cilastatin (IMI-CIL) in hospitalized adult patients with cUTI or acute pyelonephritis (AP) (Figure 1). The primary endpoint of overall response (clinical cure plus microbiological eradication) at test-of-cure (TOC) was assessed in the microbiological intent-to-treat (micro-ITT) population. An interim analysis to assess efficacy and futility was reviewed by an Independent Data Monitoring Committee and the study was stopped for efficacy.
Results
Baseline characteristics were balanced between treatment groups (Table 1). Overall response at TOC was 58.5% in 261/446 participants who received TBP-PI-HBr versus 60.2% in 291/483 participants who received IMI-CIL (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%). Treatment effects were comparable in participants with ESBL+ Enterobacterales (Table 2). The safety profile of TBP-PI-HBr was overall consistent with IMI-CIL; the two most frequent treatment-emergent adverse events were diarrhea and headache (Table 3).
Conclusion
Oral TBP-PI-HBr was non-inferior to IV IMI-CIL in the treatment of cUTI or AP and showed comparable efficacy in participants with ESBL+ Enterobacterales. No new safety signals were identified. TBP-PI-HBr may provide an effective oral treatment option for cUTI or AP.
Funding: PIVOT-PO was funded by Spero Therapeutics, Inc. The development of TBP-PI-HBr is supported in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201800015C.
Disclosures
All Authors: No reported disclosures