title: Safety and Activity of UR-1505 in Atopic Dermatitis: A Randomized, Double-blind Phase II Exploratory Trial.
abstract: OBJECTIVE
  UR-1505 is a new small molecule with immune modulator properties intended for the topical treatment of inflammatory skin diseases that has shown anti-inflammatory effects in models of skin inflammation. We compared the activity of UR-1505 ointment against its vehicle in the treatment of atopic dermatitis. Secondary objectives included exploring dose response, safety, and local tolerability of UR-1505.
  
  
  METHODS
  Patients with AD lesions on 2 symmetrical topographic areas (arms, leg, or trunk) were included in this unicenter randomized, double-blind, within-patient, controlled Phase II exploratory trial and received simultaneously 2 different treatments (0.5%, 1%, or 2% UR-1505 and vehicle or 0.1% tacrolimus ointment) once daily during 28 days. The primary efficacy end point was the change from baseline in the Investigator Global Assessment score at Day 28. Secondary end points were percentage of area clearance, local Eczema Area Severity Index (local EASI), and local tolerability. A linear mixed model was used, fitting treatment, body side, and group (treatment at the contralateral side) as fixed factors and the patient as a random effect.
  
  
  RESULTS
  Twenty-eight patients were randomized and 25 patients were included in the per protocol analysis, with 50 evaluable lesions (n = 13 for vehicle, n = 8 for UR-1505 0.5%, n = 9 for 1% UR-1505, n=8 for 2% UR-1505, and n=12 for tacrolimus). The mean Investigator Global Assessment score change from baseline at Day 28 was -1.7 for vehicle, -1.0, -1.2, and -1.5 for 0.5%, 1%, and 2% UR-1505, respectively, and -2.6% for tacrolimus (P = 0.002). No serious nor causal adverse reactions were reported in this study, but patients reported numerous local symptoms after product applications, especially itching, tingling, tightness, and heat/burning sensations at frequencies that were similar for vehicle, 1% UR-1505, and 2% UR-1505; more frequent with 0.5% UR-1505; and lowest for tacrolimus.
  
  
  CONCLUSIONS
  This study found that UR-1505 may not be a suitable option for the treatment of atopic dermatitis due to its lack of clinically relevant effect compared with its vehicle and 0.1% tacrolimus ointment.
authors.affiliation: Clinical Pharmacology Unit(,) Hospital de Sabadell, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell (Barcelona), Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Vives
authors.affiliation: Clinical Pharmacology Unit(,) Hospital de Sabadell, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell (Barcelona), Spain. Electronic address: caridad.pontes@uab.cat.
authors.forename: Caridad
authors.initials: C
authors.lastname: Pontes
authors.affiliation: Merck Sharp & Dohme, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Sarasa
authors.affiliation: Creativ-Ceutical, Paris, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Millier
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009824:Ointments; D012459:Salicylates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult; D005466:Fluorocarbons
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D009824:Ointments; D012459:Salicylates; D016559:Tacrolimus; C522458:2-hydroxy-4-(2,2,3,3,3-pentafluoropropoxy)benzoic acid; D005466:Fluorocarbons
keywords: Phase II; anti-inflammatory agents; atopic; clinical trial; dermatitis; eczema