title: A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon.
abstract: OBJECTIVE
  MQX-503 is a novel nitroglycerine preparation designed to absorb quickly and allow local vasodilatation in the skin. We examined the efficacy and tolerability of this medication in Raynaud phenomenon (RP) in a laboratory-based study.
  
  
  METHODS
  In this multi-centre, double-blind, randomised, placebo-controlled, cross-over study, subjects were treated with 0.5% or 1.25% nitroglycerine or placebo gel. Subjects received each dose twice in a randomised order. Each study session consisted of baseline laser Doppler measurements, study gel application and 5 min of cold chamber exposure (-20°C). Blood flow (BF) was measured at the end of exposure and for the next 120 min at set intervals. Other outcome measures included achievement of baseline BF; the time to achieve 50% and 70% baseline skin temperature (ST); and pain, tingling and numbness scores.
  
  
  RESULTS
  37 subjects completed 214 treatment periods. Time to achieve baseline BF was significantly shorter in the two treated groups (HR=1.77 and 2.02 for 0.5% and 1.25% vs placebo, respectively). The proportion of subjects achieving baseline BF was 45.8% for placebo, 66.2% for 0.5% and 69% for 1.25% (p=0.01 and p=0.002 for 0.5% and 1.25% vs placebo, respectively). No meaningful differences were seen in ST or pain/numbness/tingling scores. Treatment was well tolerated with no serious adverse events.
  
  
  CONCLUSIONS
  Treatment with MQX-503 caused a significant improvement in skin BF compared with placebo. Data from this proof of concept study suggest benefit of MQX-503 in subjects with RP.
authors.affiliation: Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, , Baltimore, Maryland, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Hummers
authors.forename: Carin E
authors.initials: CE
authors.lastname: Dugowson
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Dechow
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gregory
authors.forename: Joel
authors.initials: J
authors.lastname: Michalek
authors.forename: Gayane
authors.initials: G
authors.lastname: Yenokyan
authors.forename: John
authors.initials: J
authors.lastname: McGready
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011928:Raynaud Disease / Q000188:drug therapy* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D012881:Skin Temperature / Q000187:drug effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D005782:Gels; D014665:Vasodilator Agents; D005996:Nitroglycerin