CHICAGO – Prucalopride, a high-affinity serotonin 5-hydroxytryptamine4 receptor agonist, proved effective for the treatment of severe chronic constipation in men in a phase III clinical trial.
In this randomized, 66-site European trial involving 358 subjects on once-daily prucalopride at 2 mg or placebo, 37.9% of the prucalopride group achieved the primary endpoint of a mean of at least three spontaneous complete bowel movements per week over the course of the 12-week treatment period, significantly better than the 17.7% rate in controls, reported Dr. Kevin Etherson of Durham (England) University.
Bruce Jancin/Frontline Medical News
Dr. Kevin Etherson
This was no small feat, he noted. Participants had a mean 9.2-year duration of chronic constipation. One-third of controls and 42% of the prucalopride group had experienced less than one spontaneous complete bowel movement per week during the 6 months prior to enrollment.
Prucalopride is already approved in the European Union for the treatment of chronic constipation in women for whom laxatives fail to provide adequate relief. The new phase III data pave the way for an expanded European indication including men. As for when U.S. physicians can expect to be able to prescribe the drug, a Shire spokesperson said the company is "working with the FDA [Food and Drug Administration] to create a regulatory pathway forward."
The new phase III results were consistent with the outcomes seen in the four published pivotal phase III trials conducted with the same endpoints in women, Dr. Etherson said at the annual Digestive Disease Week.
At baseline, 68% of the prucalopride group rated their constipation as "severe" or "very severe." After 12 weeks of active treatment, that was the case for only 22% of the men. At follow-up, 47% of the prucalopride group rated their global treatment efficacy as "quite a bit" or "extremely effective," compared with 30% of placebo-treated controls.
No significant ECG changes occurred during the study. Six men discontinued prucalopride, and seven stopped taking placebo. Gastrointestinal adverse events – mostly diarrhea, nausea, and abdominal pain – were reported by 20% of the men on prucalopride and 14% of the controls. Headaches and dizziness were also more common in the prucalopride group.
The phase III study was sponsored by Shire. Dr. Etherson reported having no financial conflicts of interest.