A two-part phase I study to establish and compare the safety and local tolerability of two nasal formulations of XF-73 for decolonization of Staphylococcus aureus: A previously investigated 0.5 mg/g viscosified gel formulation versus a modified formulation

Abstract Objectives There is conflicting data on the success of mupirocin as an effective decolonizing regimen forStaphylococcus aureus (SA) carriage, in part due to increasing drug resistance. This multi-center, randomized, open-label, prospective phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial drug with rapid intrinsic activity against SA. Methods The study was conducted in 2 dosing cohorts, and enrolled 60 healthy adults. In Part 1, 8 non-SA carriers were randomized to 2 groups of 4 subjects in each arm and were treated with the new formulations of XF-73 in concentrations of 0.5 mg/g 2% gel and 2 mg/g 2% gel, respectively. In Part 2, 52 healthy persistent SA carriers were randomized to 4 groups of 13 subjects in each arm and were treated with three different concentrations of XF-73 (0.5 mg/g 2% gel, 2 mg/g 2% gel and 0.5 mg/g 4% gel) or a 4% viscosified placebo gel, respectively. Plasma pharmacokinetics (PK) and pharmacodynamics (PD) studies were performed. Anti-staphylococcal activity was assessed as the presence or absence of SA and by quantification of the level of colonization using a semi-quantitative scale (SA score). Results 56 subjects (8/8 from Part 1 and 48/52 from Part 2) completed the study, with 47/60 comprising the PK population and 48/60 the PD population. There was no measurable systemic absorption of XF-73 from nasal application. Treatment with XF-73 was associated with a rapid diminution in the SA scores in all subjects. The most common treatment emergent adverse events (TEAE) reported were rhinorrhea and nasal dryness (15.5% each in Part 1 and Part 2). TEAEs were mostly mild and resolved spontaneously. Conclusion XF-73 was found to be safe and was tolerated with minimal side effects at doses of 0.5 mg/g 2% gel and 2 mg/g 2% gel in healthy volunteers. These findings support moving on to Phase 2 trials to further evaluate the efficacy of XF-73.