George A Yendewa1, J McLeod Griffiss2, Michael R Jacobs3, Scott A Fulton4, Mary Ann O'Riordan5, Wesley A Gray6, Howard M Proskin7, Peter Winkle8, Robert A Salata4. 1. Department of Medicine and Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA. Electronic address: gay7@case.edu. 2. ClinicalRM, Hinckley, OH, USA. 3. Department of Pathology, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 4. Department of Medicine and Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA. 5. Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. 6. Department of Pediatrics, University of Toledo, Toledo, OH, USA. 7. Howard M. Proskin and Associates, Incorporated, Rochester, NY, USA. 8. Anaheim Clinical Trials, Anaheim, CA, USA.
Abstract
OBJECTIVES: Successful decolonisation of nasal Staphylococcus aureus (SA) carriage by mupirocin is limited by increasing drug resistance. This randomised, open-label, phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial with rapid intrinsic activity against SA. METHODS: The study was performed in 60 healthy adults. In Part 1, eight non-SA carriers were randomised to groups of four subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel or 2.0mg/g 2% gel. In Part 2, 52 persistent SA carriers were randomised to groups of 13 subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel, 2.0mg/g 2% gel, 0.5mg/g 4% gel or 4% viscosified placebo gel. Plasma pharmacokinetic and pharmacodynamic studies were performed. Antistaphylococcal activity was assessed as the presence/absence of SA and by quantification of colonisation using a semiquantitative 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 pharmacokinetic population and 48/60 the pharmacodynamic population. There was no measurable systemic absorption of XF-73. XF-73 treatment was associated with rapid reduction in SA score in all subjects. The most common treatment-emergent adverse events (TEAEs) were rhinorrhoea and nasal dryness (15.5% each in Parts 1 and 2). TEAEs were mild and resolved spontaneously. CONCLUSION:XF-73 was well tolerated with minimal side effects at doses of 0.5mg/g 2% gel and 2.0mg/g 2% gel. These findings support further development of XF-73.
RCT Entities:
OBJECTIVES: Successful decolonisation of nasal Staphylococcus aureus (SA) carriage by mupirocin is limited by increasing drug resistance. This randomised, open-label, phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial with rapid intrinsic activity against SA. METHODS: The study was performed in 60 healthy adults. In Part 1, eight non-SA carriers were randomised to groups of four subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel or 2.0mg/g 2% gel. In Part 2, 52 persistent SA carriers were randomised to groups of 13 subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel, 2.0mg/g 2% gel, 0.5mg/g 4% gel or 4% viscosified placebo gel. Plasma pharmacokinetic and pharmacodynamic studies were performed. Antistaphylococcal activity was assessed as the presence/absence of SA and by quantification of colonisation using a semiquantitative 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 pharmacokinetic population and 48/60 the pharmacodynamic population. There was no measurable systemic absorption of XF-73. XF-73 treatment was associated with rapid reduction in SA score in all subjects. The most common treatment-emergent adverse events (TEAEs) were rhinorrhoea and nasal dryness (15.5% each in Parts 1 and 2). TEAEs were mild and resolved spontaneously. CONCLUSION:XF-73 was well tolerated with minimal side effects at doses of 0.5mg/g 2% gel and 2.0mg/g 2% gel. These findings support further development of XF-73.
Authors: G I Andriesse; M van Rijen; D Bogaers; A M C Bergmans; J A J W Kluytmans Journal: Eur J Clin Microbiol Infect Dis Date: 2009-06-28 Impact factor: 3.267
Authors: Lonneke G M Bode; Jan A J W Kluytmans; Heiman F L Wertheim; Diana Bogaers; Christina M J E Vandenbroucke-Grauls; Robert Roosendaal; Annet Troelstra; Adrienne T A Box; Andreas Voss; Ingeborg van der Tweel; Alex van Belkum; Henri A Verbrugh; Margreet C Vos Journal: N Engl J Med Date: 2010-01-07 Impact factor: 91.245
Authors: Jeffrey C Jones; Theodore J Rogers; Peter Brookmeyer; William Michael Dunne; Gregory A Storch; Craig M Coopersmith; Victoria J Fraser; David K Warren Journal: Clin Infect Dis Date: 2007-07-13 Impact factor: 9.079