title: Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections.
abstract: Gepotidacin is a novel, first-in-class, triazaacenaphthylene antibacterial agent which hasin vitroactivity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs). This phase 2, randomized, 2-part, multicenter, dose-ranging, response-adaptive study with optional intravenous-oral switch evaluated the efficacy and safety of gepotidacin for the treatment of Gram-positive ABSSSIs in 122 adult patients in the United States. The study had a double-blind phase (part 1; intravenous [750 mg or 1,000 mg every 12 h {q12h}]) and an open-label phase (part 2; intravenous [750 mg q12h, 1,000 mg q12h, or 1,000 q8h]). The primary endpoint was a composite of efficacy and safety which consisted of the early cure rate and the withdrawal rate due to drug-related adverse events and utilized a clinical utility index for dose selection. At the early efficacy visit (48 to 72 h after the first dose), the 750-mg q12h and 1,000-mg q8h groups met prespecified success criteria for clinical utility in terms of efficacy and safety; however, the 1,000-mg q12h group did not meet these criteria due to observed lower efficacy rates. The most frequently reported adverse events were nausea (20%) and diarrhea (13%). These encouraging phase 2 results demonstrate the potential for gepotidacin to meet the medical need for novel antibacterial agents to treat ABSSSIs due to drug-resistant pathogens through a unique mechanism of action. (This study has been registered at ClinicalTrials.gov under registration no. NCT02045797.).
authors.affiliation: eStudySite, San Diego, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: O'Riordan
authors.affiliation: GlaxoSmithKline, Upper Providence, Pennsylvania, USA Courtney.A.Tiffany@gsk.com Etienne.f.dumont@gsk.com.
authors.forename: Courtney
authors.initials: C
authors.lastname: Tiffany
authors.affiliation: GlaxoSmithKline, Upper Providence, Pennsylvania, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Scangarella-Oman
authors.affiliation: GlaxoSmithKline, Upper Providence, Pennsylvania, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Perry
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hossain
authors.affiliation: GlaxoSmithKline, Upper Providence, Pennsylvania, USA.
authors.forename: Teri
authors.initials: T
authors.lastname: Ashton
authors.affiliation: GlaxoSmithKline, Upper Providence, Pennsylvania, USA Courtney.A.Tiffany@gsk.com Etienne.f.dumont@gsk.com.
authors.forename: Etienne
authors.initials: E
authors.lastname: Dumont
mesh_terms: D000073:Acenaphthenes / Q000627:therapeutic use*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000472:pathogenicity*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000073:Acenaphthenes; D000900:Anti-Bacterial Agents; D006575:Heterocyclic Compounds, 3-Ring; C000612856:gepotidacin
keywords: ABSSSI; antibacterial agent; antimicrobial safety; efficacy; gepotidacin; phase 2 study; skin infections