Linaclotide reduces symptoms for patients with chronic constipation, studies show

Linaclotide, an investigational drug for the relief of chronic constipation, appears to be effective and safe, according to the results of two phase 3 trials published in the August issue of the New England Journal of Medicine.

Two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials were conducted from August 20, 2008, through August 12, 2009 to assess efficacy and safety of the drug. Patients were randomly assigned to receive 145 µg or 290 µg of linaclotide or placebo administered once daily in the form of an oral capsule.

The primary end point of each trial was defined as including 3 or more complete spontaneous bowel movements (CSBMs) per week and an increase of at least 1 CSBM per week from baseline for at least 9 of the 12-week treatment period. Secondary end points included stool frequency (weekly rates of CSBMs and SBMs), stool consistency, severity of straining, abdominal discomfort, bloating, and constipation severity.

The primary end point was reached by 21.2% of patients in Trial 303 and 16% of patients in trial 01 who received the 145-µg dose of linaclotide and 19.4% (Trial 303), and 21.3% (Trial 01) of the patients who received the 290-µg dose of linaclotide. Of patients receiving placebo, 3.3% (Trial 303) and 6% (Trial 01) achieved primary end points (P<.01 for each linaclotide dose, as compared with placebo, for each trial). Patients who received linaclotide had significant improvements in all secondary end points from baseline to week 12 compared with patients receiving placebo. Researchers also noted significant improvements in the overall and component PAC-QOL scores for patients on both linaclotide doses compared with placebo (with the exception of psychosocial discomfort in Trial 303 for patients given the 290-µg dose).

The most common adverse event was diarrhea, which led to discontinuation of treatment by 4.7% and 3.8% of patients who received 145 µg and 290 µg of linaclotide, respectively, vs 0.5% in the placebo group.

“In these two, large phase 3 trials involving patients with chronic constipation, linaclotide led to improvement in bowel and abdominal symptoms and reduced the severity of constipation. Linaclotide has the potential to offer multisymptom relief to patients with chronic constipation,” the authors concluded.