LB-7. Meropenem-Vaborbactam (M-V) Compared with Piperacillin-Tazobactam (P-T) in the Treatment of Adults with Complicated Urinary Tract Infections (cUTI), including Acute Pyelonephritis (AP) in a Phase 3 Randomized, Double-blind, Double-dummy Trial (TANGO 1)
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 29, 2016: 11:30 AM
Room: 283-285
Background: Vaborbactam (formerly RPX7009) is a new class of beta-lactamase inhibitor that is being developed in combination with meropenem. The combination has potent activity against KPC-producing carbapenem-resistant Enterobacteriaceae and is being developed to treat serious gram-negative infections, including cUTI.

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.

Conclusion: M-V was statistically superior to P-T for the FDA primary endpoint of overall success at the EOIVT in the treatment of patients with cUTI/AP. M-V was well tolerated, with an adverse event profile similar to P-T.

Jeff Loutit, MBChB1, Karen Fusaro, BA2, Shu Zhang, PhD2, Elizabeth Morgan, BS1, Elizabeth Alexander, MD, MSc.2, David Griffith, BS1, Olga Lomovskaya, PhD1 and Michael N. Dudley, Pharm.D.1, (1)The Medicines Company, San Diego, CA, (2)The Medicines Company, Parsippany, NJ

Disclosures:

J. Loutit, The Medicines Company: Employee , Salary

K. Fusaro, The Medicines Company: Employee , Salary and stock options

S. Zhang, The Medicines Company: Employee , Salary

E. Morgan, The Medicines Company: Employee , Salary

E. Alexander, The Medicines Company: Employee , Salary

D. Griffith, The Medicines Company: Employee , Salary

O. Lomovskaya, The Medicines Company: Employee , Salary

M. N. Dudley, The Medicines Company: Employee , Salary and stock options

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.