Ironwood and Forest report positive results from Phase IIb IBS-C 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 change from baseline versus placebo for complete spontaneous bowel movement (CSBM) frequency-the study’s primary endpoint-was clinically and statistically significant (2.5 to 3.6 versus 1.0; p = 0.0036 to <0.0001). In addition, abdominal pain was clinically and 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 global assessments were statistically significant for the 300ug and 600ug dose groups and for at least one of the two lower doses for each endpoint. Treatment effects of linaclotide were rapid in onset and were maintained throughout the entire 12-week treatment period; there was no indication of rebound clinical effects following cessation of treatment. Linaclotide was well tolerated at all doses with no treatment-related serious adverse events.