Dr Michael Camilleri and colleagues from Minnesota, USA conducted a phase 3 trial of 12 weeks duration to determine the efficacy of prucalopride in patients with severe chronic constipation.
Prucalopride is a selective, high-affinity 5-hydroxytryptamine4 receptor agonist.
|47% on prucalopride had an increased complete bowel movements of 1 or more per week|
|New England Journal of Medicine|
Patients with severe chronic constipation received placebo or 2 or 4 mg of prucalopride, once daily, for 12 weeks.
The primary efficacy end point was the proportion of patients having 3 or more spontaneous, complete bowel movements per week, averaged over 12 weeks.
Secondary efficacy end points were derived from daily diaries and validated questionnaires completed by patients.
Adverse events, clinical laboratory values, and cardiovascular effects were monitored.
The researchers analyzed efficacy in 620 patients.
The proportion of patients with 3 or more spontaneous, complete bowel movements per week was 31% of those receiving 2 mg of prucalopride, and 28% of those receiving 4 mg of prucalopride.
The proportion of patients with 3 or more spontaneous, complete bowel movements per week as compared with 12% in the placebo group.
The team found that 47% of patients in each group receiving 2 mg or 4 mg of prucalopride had an increase in the number of spontaneous, complete bowel movements of 1 or more per week.
The research team noted that spontaneous, complete bowel moevements of 1 or more a week was 26% in the placebo group.
Secondary efficacy end points including patients' satisfaction with their bowel function, and treatment and their perception of the severity of their constipation symptoms.
The team observed that secondary endpoints were significantly improved with the use of 2 or 4 mg of prucalopride as compared with placebo, at week 12.
The most frequent treatment-related adverse events were headache and abdominal pain.
The researchers observed no significant cardiovascular effects of treatment.
Dr Camilleri's team concluded, "Over 12 weeks, prucalopride significantly improved bowel function and reduced the severity of symptoms in patients with severe chronic constipation."
"Larger and longer trials are required to further assess the risks and benefits of the use of prucalopride for chronic constipation."