Phase IIIb trial of Linzess meets endpoints in irritable bowel syndrome with constipation

Ironwood Pharmaceuticals and Allergan announced positive topline data from a Phase IIIb clinical trial evaluating Linzess (linaclotide) 290 mcg on multiple abdominal symptoms in adult patients with Irritable Bowel Syndrome with Constipation (IBS-C). The trial met its primary multi-component endpoint and demonstrated that linaclotide improved the overall abdominal symptoms of bloating, pain and discomfort in adult IBS-C patients compared to placebo. The trial also met both secondary endpoints.

This trial was designed to highlight the impact of Linzess on the overall abdominal symptoms of bloating, pain and discomfort, which are part of patients’ reported real-world experience, thereby enabling better communication about these symptoms. Topline data from a randomized, double-blind, placebo-controlled Phase IIIb trial showed that linaclotide 290 mcg administered orally once daily demonstrated a statistically significant and clinically meaningful improvement in overall abdominal symptoms compared to placebo across the primary and both secondary endpoints. In the multi-component primary endpoint, linaclotide-treated patients showed a 29.7% mean decrease from baseline in their weekly abdominal score (bloating, pain and discomfort) through the 12-week treatment period, compared to 18.3% for the placebo-treated patients (p<0.0001). In the secondary endpoints, 40.5% of patients treated with linaclotide 290 mcg demonstrated a clinically meaningful response, as defined by the abdominal symptom score responder, compared to 23.4% of placebo-treated patients (p<0.0001). An abdominal symptom score responder was defined as a patient who experienced an improvement of at least two-points from baseline in their weekly abdominal score for at least six of 12 weeks of treatment period. These findings add to the significant body of data supporting the impact of linaclotide on the overall abdominal symptoms of bloating, pain and discomfort in adult IBS-C patients.

Linaclotide was well-tolerated in this Phase IIIb study, with the most commonly reported adverse event being diarrhea. During the treatment period, diarrhea was reported in 4.6% of patients on linaclotide 290 mcg as compared to 1.6% of patients on placebo. Study discontinuation resulting from diarrhea occurred in 1.6% of linaclotide 290 mcg patients compared to none of the placebo-treated patients.