title: RDP58 is a novel and potentially effective oral therapy for ulcerative colitis.
abstract: BACKGROUND
  RDP58 is a novel anti-inflammatory d-amino acid decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex. We therefore evaluated its efficacy and safety in parallel multicenter, double-blind, randomized concept studies in ulcerative colitis (UC).
  
  
  METHODS
  In the first trial, 34 patients with mild to moderate active UC were randomized (1:2) to placebo (n = 13) or RDP58 100 mg (n = 21). In the second trial, 93 similar patients were randomized (1:1:1) to placebo (n = 30) RDP58 200 mg (n = 31), or RDP 300 mg (n = 32). In both studies, treatment success was defined as a simple clinical colitis activity index score of no more than 3 at 28 days. Sigmoidoscopy and rectal biopsy (at baseline and 28 days) and safety measures (baseline and 28 and 56 days) were other endpoints.
  
  
  RESULTS
  Treatment success on RDP 100 mg was 29% versus 46% on placebo (P = 0.46). There were no significant differences in sigmoidoscopy or histology score. In the second study, treatment success on the higher doses of RDP58 (200 and 300 mg) was 71% and 72%, respectively, versus 43% on placebo (P = 0.016). Improvements in sigmoidoscopy scores (41% on 200 mg and 46% on 300 mg versus 32% on placebo) did not reach significance, but histology scores improved significantly (P = 0.002) versus placebo. Overall, adverse events were no different between placebo (3.3 +/- 2.4) and RDP58 (2.7 +/- 1.4, 300-mg group).
  
  
  CONCLUSIONS
  RDP58 at a dose of 200 or 300 mg, but not 100 mg, was effective in mild-to-moderate UC. RDP58 was safe and well tolerated, and its novel action makes it an attractive potential therapy.
authors.affiliation: Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. simon.travis@orh.nhs.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Travis
authors.forename: Lee Min
authors.initials: LM
authors.lastname: Yap
authors.forename: Chris
authors.initials: C
authors.lastname: Hawkey
authors.forename: Bryan
authors.initials: B
authors.lastname: Warren
authors.forename: Mirella
authors.initials: M
authors.lastname: Lazarov
authors.forename: Tim
authors.initials: T
authors.lastname: Fong
authors.forename: R J
authors.initials: RJ
authors.lastname: Tesi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D003113:Colonoscopy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D010455:Peptides; C092373:allotrap