ototopical drops containing a novel antibacterial synthetic peptide: safety and efficacy in aduts with chronic suppurative otitis media

Objective Chronic suppurative otitis media (CSOM) is a chronic infectious disease with worldwide prevalence and that causes hearing loss and decreased quality of life. As current (antibiotic) treatments are often not successful and antibiotic resistance is emerging, alternative agents and/or strategies are urgently needed. We considered the synthetic antimicrobial and anti-biofilm peptide P60.4Ac an interesting candidate as it also displays anti-inflammatory activities including lipopolysaccharide-neutralizing activity. The aim of the present study was to investigate the safety and efficacy of ototopical drops containing P60.4Ac in adults with CSOM without cholesteatoma. Methods We conducted a limited dose-finding study and subsequently a randomized, double blinded, placebo-controlled, multicenter phase IIa study. P60.4Ac-containing or placebo ototopical drops were applied twice a day for 2 weeks and adverse events (AEs) and medication use were recorded; laboratory tests, swabs from the middle ear and throat for bacterial cultures, and audiometry were performed at various intervals up to 10 weeks after therapy. Response to treatment was assessed by blinded symptom scoring on otoscopy. Results Direct application of P60.4Ac-containing ototopical drops (range 0.25-2.0 mg of peptide/ml) on the tympanic membrane was safe and well-tolerated. The optimal dose , i.e.0.5 mg of peptide/ml, was selected for the subsequent phase IIa study. Safety evaluation revealed only a few AEs that were unlikely related to study treatment and all, except one, were of mild to moderate intensity. Further to this excellent safety profile, P60.4Ac ototopical drops resulted in a treatment success in 47% of cases, versus 6% in the placebo group. Conclusion The efficacy/safety balance assessed in the present study provides a compelling justification for continued clinical development of P60.4Ac in therapy-resistant CSOM.