title: The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis.
abstract: OBJECTIVE
  To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.
  
  
  METHODS
  One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture.
  
  
  RESULTS
  A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed.
  
  
  CONCLUSIONS
  Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase 3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.
authors.forename: Mirna E
authors.initials: ME
authors.lastname: Toledo-Bahena
authors.forename: Alicia
authors.initials: A
authors.lastname: Bucko
authors.forename: Jorge
authors.initials: J
authors.lastname: Ocampo-Candiani
authors.forename: Maira E
authors.initials: ME
authors.lastname: Herz-Ruelas
authors.forename: Terry M
authors.initials: TM
authors.lastname: Jones
authors.forename: Michael T
authors.initials: MT
authors.lastname: Jarratt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pollak
authors.forename: Lee T
authors.initials: LT
authors.lastname: Zane
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001895:Boron / Q000008:administration & dosage* / Q000009:adverse effects; D001896:Boron Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004890:Erythema / Q000139:chemically induced; D005260:Female; D005533:Foot Dermatoses / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014009:Onychomycosis / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C512998:tavaborole; D001895:Boron