title: REFINE-1, a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial With ATX-101, an Injectable Drug for Submental Fat Reduction.
abstract: BACKGROUND
  ATX-101, an injectable form of deoxycholic acid, is approved in the United States and Canada for submental fat (SMF) reduction.
  
  
  OBJECTIVE
  To report results of REFINE-1, a randomized, double-blind, placebo-controlled, Phase 3 trial investigating the efficacy and safety of ATX-101.
  
  
  METHODS
  Subjects dissatisfied with their moderate or severe SMF received ATX-101 (2 mg/cm) or placebo. Coprimary outcome measures were composite ≥1-grade and ≥2-grade improvements in clinician-assessed and subject-assessed SMF severity using validated scales at 12 weeks after last treatment. Magnetic resonance imaging (MRI) provided an objective measure of submental volume reduction. Patient-reported outcomes were assessed.
  
  
  RESULTS
  Among 256 ATX-101-treated and 250 placebo-treated subjects, a ≥1-grade composite response was achieved in 70.0% and 18.6%, and a ≥2-grade composite response in 13.4% and 0%, respectively (p < .001 for both). The proportion of MRI responders was more than 8 times higher with ATX-101 than placebo (46.3% vs 5.3%; p < .001). ATX-101-treated subjects reported improvement in the psychological impact of SMF and satisfaction with treatment (p < .001 for all assessments vs placebo). Of note, 55% and 75% of ATX-101-treated subjects reported 1-grade improvement in clinician-assessed SMF after 2 and 4 treatments, respectively. Adverse events (primarily localized to the injection site) were mostly mild or moderate, and transient. Marginal mandibular nerve paresis reported in 4.3% of ATX-101-treated subjects (1.0% of all ATX-101 treatment sessions) was mostly mild, transient, and resolved without sequelae.
  
  
  CONCLUSIONS
  ATX-101 is a safe and efficacious, first-in-class, injectable drug for SMF reduction.
authors.affiliation: *Dermatology Division, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; †Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada; ‡Department of Head and Neck Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; §Department ofDermatology, Howard University College of Medicine, Washington, DC; ‖Kythera Biopharmaceuticals, Inc., Westlake Village, California (now an affiliate of Allergan plc, Irvine, California); ¶Evidence Scientific Solutions, Philadelphia, Pennsylvania.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Jones
authors.forename: Jean
authors.initials: J
authors.lastname: Carruthers
authors.forename: John H
authors.initials: JH
authors.lastname: Joseph
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Callender
authors.forename: Patricia
authors.initials: P
authors.lastname: Walker
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Lee
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Subramanian
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lizzul
authors.forename: Todd M
authors.initials: TM
authors.lastname: Gross
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Beddingfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002680:Chin / Q000033:anatomy & histology; D003357:Cosmetic Techniques; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D050151:Subcutaneous Fat / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000599116:ATX-101 compound; D003840:Deoxycholic Acid