title: Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.
abstract: BACKGROUND
  Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.
  
  
  METHODS
  In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).
  
  
  RESULTS
  In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.
  
  
  CONCLUSIONS
  Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).
authors.affiliation: Digestive Disease Center of Excellence, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sasaki
authors.forename: Toyomitsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takano
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D019804:Mesalamine / Q000737:chemistry / Q000627:therapeutic use*; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012074:Remission Induction; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D019804:Mesalamine