Method: TANGO 1 is a Phase 3, randomized, double-blind, double dummy trial in patients with cUTI, including AP. Patients 18 years and older meeting the diagnosis of cUTI or AP were randomized 1:1 to receive M-V (2g/2g via a 3 hr infusion) or P-T (4g/0.5g via a 30 min infusion) every 8 hrs. After a minimum of 15 doses, patients in both arms could be switched to oral levofloxacin if they met pre-specified criteri, a to complete 10 days of total treatment. Enrollment was stratified based on infection type and region. The primary endpoint for the FDA was overall success [OS], a composite of clinical cure and microbial eradication, at the End of IV therapy (EOIVT) in the microbiologic modified intent to treat (mMITT) population (popn), with a pre-specified non-inferiority (NI) margin of 15%. It was pre-specified that if NI was met, an assessment for superiority would be performed.
Result: 550 patients were enrolled; 545 (99.1%) in the MITT popn and 374 (68%) had a baseline pathogen and were included in the mMITT popn. In the mMITT popn, 221 (59.1%) of patients were enrolled with AP, and 153 (40.9%) with cUTI. Overall success occurred in 189 (98.4%) of 192 randomized to M-V and 171 (94.0%) of 182 in the P-T group (95% CI of difference: 0.7, 9.1) at the EOIVT (primary endpoint). At the test of cure visit (5-9 days after completion of treatment) OS was observed in 143 (74.5%) of 192 M-V patients vs 128 (70.3%) of 182 (95% CI -4.9, 13.2). AEs were reported in 106 (39.0%) patients receiving M-V vs 97 (35.5%) on P-T, with the majority being mild or moderate in severity. Discontinuations from study drug due to an AE occurred in 7 (2.6%) on M-V and 14 (5.1%) on P-T. SAEs were reported in 11 (4.0%) receiving M-V vs 12 (4.4%) on P-T. Two deaths occurred in each group.
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