Data from two phase III trials assessing the efficacy and safety of the investigational drug linaclotide in patients with chronic constipation (CC) were presented at the Digestive Disease Week (DDW) conference.

A total of 1,276 patients who met modified Rome II criteria for CC were randomised to receive oral once-daily dosing of linaclotide (133 mcg or 266 mcg) or placebo for 12 weeks in two similarly designed double-blind Phase 3 trials (Trials 01 and 303). The average age of the patients was 48 years, 89% were female, and 76% were Caucasian.

The primary endpoint for both trials was complete spontaneous bowel movement (CSBM), defined as a patient achieving three or more CSBMs per week and an increase of at least one CSBM per week from baseline for at least nine of the 12 weeks in the trial.

In Trial 01, 16% of patients receiving 133 mcg of linaclotide and 21.3% of patients receiving 266 mcg of linaclotide met the primary endpoint compared to 6.0% in the placebo group (p=0.0012 and p<0.0001, respectively). In Trial 303, 21.2 and 19.4% of linaclotide patients met the primary endpoint compared to 3.3% in the placebo group (p<0.0001 for each dose).

Statistical significance was also achieved for all secondary endpoints versus placebo, which included measures of bloating, abdominal discomfort, weekly spontaneous bowel movements (SBMs), and weekly CSBMs. Treatment responses occurred within one week and were sustained over the 12-week treatment period. Across both trials, the most common AEs were diarrhoea, flatulence, and abdominal pain.

Linaclotide is a guanylate cyclase type C (GC-C) agonist in Phase 3 clinical development for the treatment of irritable bowel syndrome with constipation and CC.