Linaclotide Effective and Safe for Chronic Constipation- Medscape report
Linaclotide Effective and Safe for Chronic Constipation Nancy A. Melville
August 11, 2011 — The investigative drug linaclotide has been shown in 2 phase 3 placebo-controlled trials to safely and effectively reduce bowel and abdominal symptoms associated with chronic constipation, according to data published this week in the New England Journal of Medicine.
In the 2 parallel-group 12-week, double-blind, multicenter trials, 1276 patients with chronic constipation were randomized to receive either placebo or linaclotide 145 μg or 290 μg once daily.
The results indicated that at week 12, the primary endpoint of 3 or more complete spontaneous bowel movements (CSBMs) per week and an increase of 1 or more CSBMs from baseline during at least 9 of the 12 weeks was reached by 21.2% and 16.0%, respectively, of the patients who received 145 μg of linaclotide and by 19.4% and 21.3%, respectively, of the patients who received 290 μg of linaclotide.
In the placebo group, only 3.3% and 6.0% reached the endpoints, respectively, (P < .01 for all comparisons of linaclotide with placebo).
The study authors noted that, although the proportion of patients appeared low, the rate of patients achieving spontaneous bowel movements (SBMs) and CSBMs was impressive.
"Because of the rigor of the primary endpoint, only about 20% of the patients who received linaclotide and 5% of those who received placebo were considered to have had a response," they wrote.
"Of perhaps greater clinical relevance, the mean stool frequency in the 2 trials increased to 5.1 and 5.6 SBMs per week and to 2.2 and 2.9 CSBMs per week in the linaclotide-treated patients, as compared with 3.0 and 3.2 SBMs per week and 0.9 and 0.9 CSBMs per week in the placebo-treated patients."
The drug's effects were rapid, observed within the first 24 hours, and sustained through 16 weeks.
Importantly, patients also reported improvements in stool consistency, reduced straining, and reduced abdominal symptoms, such as bloating and discomfort, which are common concerns with chronic constipation, the study authors reported.