RESUMEN
OBJECTIVE: Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited. METHODS: This double-blind, placebo-controlled trial randomised CF patients <7â¯years (Nâ¯=â¯51) with early Pa-infection to tobramycin inhalation solution (TOBI 300â¯mg) or placebo (twice daily) for 28â¯days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29. RESULTS: On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (pâ¯<â¯0.001). At the end of the cross-over period, 76.0% patients receiving TOBI in the initial 28â¯days were Pa-free compared to 47.8% receiving placebo initially. Adverse events were consistent with the TOBI safety profile with no differences between TOBI and placebo. CONCLUSION: TOBI was effective in eradicating early Pa-infection with a favourable safety profile in young CF patients. TRIAL REGISTRATION NUMBER: NCT01082367.
Asunto(s)
Fibrosis Quística/complicaciones , Pseudomonas aeruginosa/aislamiento & purificación , Esputo/microbiología , Tobramicina/administración & dosificación , Administración por Inhalación , Antibacterianos/administración & dosificación , Niño , Preescolar , Estudios Cruzados , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/microbiología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration.