Pharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b Study.

ABSTRACT: Omadacycline, an aminomethylcycline antibiotic, is approved as once-daily intravenous (i.v.) and oral (p.o.) monotherapy for acute bacterial skin and skin structure infections and for community-acquired bacterial pneumonia, and it is under development for treatment of urinary tract infection (UTI). This is a phase 1b, randomized, open-label study of omadacycline in women with cystitis (defined as UTI symptoms and a positive urine leukocyte esterase test). Patients received omadacycline for 5?days (group 1: 200?mg intravenously on day 1, then 300?mg orally every 24?h [q24h]; group 2: 300?mg orally every 12?h [q12h] on day 1, then 300?mg orally q24h; group 3: 450?mg orally q12h on day 1, then 450?mg orally q24h). Blood and urine samples were collected over 5?days. Investigator-assessed clinical response was determined at end of treatment (EOT; day 6) and posttreatment evaluation (PTE; 5 to 9?days after last dosing). A total of 31 women were treated. At steady state (day 5), the range of mean omadacycline urine concentrations over 24?h across the groups was 17.94 to 48.12??g/ml. The most common treatment-emergent adverse events were gastrointestinal (including nausea [60% to 73%] and vomiting [20% to 40%]) and were generally mild and transient. Investigator-determined clinical success was observed in 94% and 84% of patients at EOT and PTE, respectively, with similar results across groups. A favorable microbiological response at PTE was observed in 78% of patients who had a baseline pathogen. Omadacycline is partially excreted in urine and appears to be safe and well tolerated. These preliminary results indicate that omadacycline warrants further evaluation in larger controlled UTI studies.

SUBMITTER: Overcash JS 

PROVIDER: S-EPMC6496050 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature