Prucalopride safe and effective for men with chronic constipation

Last Updated: 2015-05-18

By Larry Hand

NEW YORK (Reuters Health) - Already approved for use in women, prucalopride is also safe and effective as a treatment for chronic constipation in men, according to a new trial.

The drug, sold as Resolor by Shire, is a 5-hydroxytryptamine receptor-4 agonist and acts by stimulating intestinal motility. It is approved in Europe for treating chronic constipation in women in whom laxatives fail to provide relief, based on previous trials with mostly women participants.

"The evidence for effect is strong and equivalent to that of the previous studies, which largely recruited female patients, so I would expect this to be adequate to support (further) approval," Dr. Yan Yiannakou from County Durham and Darlington NHS Foundation Trust in Durham, UK, told Reuters Health by email.

He and colleagues recruited men 18 and older with chronic constipation for a trial involving 66 sites across Europe from September 2010 to October 2013. They randomized participants to receive prucalopride or placebo once a day. Patients younger than 65 received 2 mg, while patients 65 or older received 1 mg, with a possible boost to 2 mg.

Patients returned to treatment centers at weeks 2, 4, 8, and 12 for researchers to review daily electronic diary entries and potential progress. Researchers asked the patients at weeks 4 and 12 to complete the Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire. They also administered the Patient Assessment of Constipation-Quality of Life (PAC-QOL) the same weeks.

Among 374 patients enrolled, more patients taking prucalopride had a mean of three or more spontaneous complete bowel movements (SCBMs) weekly (37.9% vs. 17.7%, p<0.0001), over the 12-week treatment period.

At the final visit, 46.7% of prucalopride patients rated their treatment as "quite a bit" or "extremely" effective, compared with 30.4% of placebo patients (p<0.0001).

The proportion of patients who had improvement in the PAC-QOL score came to 52.7% for the prucalopride group and 38.8% for the placebo group (p=0.0035), the researchers report in the American Journal of Gastroenterology, online April 14.

At baseline, 67.6% of patients in the prucalopride group and 56.2% of patients in the placebo group characterized their constipation as severe or very severe. The corresponding percentages at 12 weeks of treatment came to 21.9% for the prucalopride group and 30.4% for the placebo group.

Seventy-eight (42.4%) of patients in the prucalopride group and 64 (34.4%) of patients in the placebo group experienced at least one treatment-emergent adverse event. Most were mild to moderately severe. One patient experienced a severe event, atrial fibrillation, in the prucalopride group, compared with four patients in the placebo group (myocardial ischemia, lower limb fracture, glottis carcinoma, and atelectasis). No deaths occurred.

"On the basis of these findings, it can be concluded that prucalopride once daily, taken for 12 weeks, is effective in the treatment of chronic constipation in men. Both the efficacy and safety results of this study were in line with observations in the overall prucalopride population studied to date, which has included predominantly female patients," the researchers write.

Dr. Yiannakou concluded, "There was no reason to expect the results to be different in male patients so in that sense the findings were not surprising."

Shire plc holds the rights to develop and market prucalopride in the U.S., where it has not been approved. A spokesperson for Shire did not respond to a request for comment by deadline.

Shire has requested a label change from the European Medicines agency based on the results of this trial. The company issued the following statement through a spokesperson:

"Pending a positive final decision from EMA in the near future on this submission, Shire plans to begin marketing Resolor in Europe with an expanded indication for symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief. With respect to the U.S., prucalopride is in phase 3 development, and Shire has agreed with (the Food and Drug Administration) on a regulatory path forward for a (new drug application) submission. Should we submit an NDA for prucalopride, we expect that we will include the data from the phase 3 clinical study in men. We continue to work towards meeting the requirements agreed between Shire and FDA and have not yet disclosed timing for a potential NDA submission."

Shire-Movetis NV funded this study and employed two coauthors at the time of the study. Dr. Yiannakou and two co-authors have reported financial ties to the company.

SOURCE: http://bit.ly/1IW0zSp

Am J Gastroenterol 2015.