Ironwood reports positive results from Phase IIb constipation trial

Analysis of the data indicates that once-daily oral dosing of linaclotide, across a range of doses, significantly reduced abdominal pain and significantly improved constipation symptoms in patients with irritable bowel syndrome with constipation (IBS-C) throughout the 12-week study period. Further, the safety and tolerability profile support advancing this novel compound into Phase III clinical trials.

Approximately 420 patients were randomized into the study and 337 completed the 12-week treatment period. At all linaclotide dose levels, the improvement from baseline versus placebo for complete spontaneous bowel movement (CSBM) frequency – the study’s primary endpoint – was statistically significant (2.5 to 3.6 versus 1)

In addition, abdominal pain was statistically significantly reduced in all linaclotide treatment groups compared to placebo (-0.7 to -0.9 change from baseline on a five-point ordinal severity scale versus -0.5; p = 0.0239 to <0.0001) and, in the 26% of patients with severe/very severe baseline abdominal pain, improvement was even more pronounced (-0.8 to -1.3 versus -0.2; p = 0.0236 to <0.0001). Results for spontaneous bowel movement (SBM) frequency, stool consistency, straining, abdominal discomfort, bloating, IBS symptom severity, and other global assessments were statistically significant for the two highest dose groups, 300ug and 600ug, and for at least one of the two lower doses, 75 and 150ug, for each endpoint. Treatment effects of linaclotide occurred within the first week of treatment and were maintained throughout the entire 12-week treatment period; there was no indication of rebound worsening of IBS symptoms following cessation of treatment. Ironwood and North American partner Forest Laboratories expect to initiate two pivotal Phase III trials in patients with IBS-C by January 2009.