A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis.
OBJECTIVE
Balsalazide is a new innovative, mesalamine-containing prodrug that is activated by bacteria in the colon. Balsalazide has been shown previously to be well tolerated and effective in the treatment of acute ulcerative colitis. The aim of this study was to determine the dose-response of balsalazide for efficacy and safety in active, mild-to-moderate ulcerative colitis and to compare this profile with that of mesalamine, pH-dependent, delayed-release tablets.


METHODS
A multicenter, randomized, active control, double-blind, double-dummy, dose-response, parallel-group study was performed comparing balsalazide (6.75 g daily), balsalazide (2.25 g daily), and mesalamine (2.4 g daily), administered for 8 wk to 154 patients with active, mild-to-moderate ulcerative colitis as verified by sigmoidoscopy.


RESULTS
Eight weeks of treatment with 6.75 g of balsalazide daily provided significantly greater improvement than did balsalazide (2.25 g daily) in rectal bleeding (64.7% [6.75-g balsalazide] vs 32.4% [2.25-g balsalazide], p < 0.006), stool frequency (58.8% vs 29.4%, p < 0.006), sigmoidoscopic score (78.9% vs 52.5%, p < 0.015), and Physician's Global Assessment (73.7% vs 51.3%, p < 0.03). The efficacy of balsalazide showed a significantly more rapid onset of action than that of mesalamine (2.4 g daily) (2-wk sigmoidocopic score improvement, 54.7% [6.75-g balsalazide] vs 29.4% [2.4-g mesalamine], p = 0.006) with numerically greater improvement at 8 wk in five of seven measured signs and symptoms. Balsalazide (6.75 g daily) was well tolerated, and the safety profile did not differ significantly from that of balsalazide (2.25 g daily) or mesalamine.


CONCLUSIONS
Eight weeks of treatment with balsalazide (6.75 g daily) is significantly more effective than balsalazide (2.25 g daily) and more rapid in onset than mesalamine (2.4 g daily) in improving signs and symptoms of acute ulcerative colitis. Balsalazide (6.75 g daily) is well tolerated, and the safety profile does not differ from that of balsalazide (2.25 g daily) and mesalamine (2.4 g daily).
Levine
Douglas S
DS
Division of Gastroenterology, University of Washington School of Medicine, Seattle, USA.
Riff
Dennis S
DS
Pruitt
Ronald
R
Wruble
Lawrence
L
Koval
George
G
Sales
David
D
Bell
John K
JK
Johnson
Lorin K
LK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000636:Aminosalicylic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006706:Homeostasis; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D008875:Middle Aged; D010659:Phenylhydrazines; D012449:Safety; D012720:Severity of Illness Index
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010659:Phenylhydrazines; D019804:Mesalamine; C038637:balsalazide