The 3.0-mg plecanatide arm also showed significant improvements in secondary endpoints, including stool consistency and straining, compared with placebo (P less than .001). In addition, that arm had significant improvements in constipation-associated symptoms and quality of life relative to baseline (P less than .001), the results showed.
The cumulative days that rescue medication was used per month also significantly decreased among patients on 3.0 mg of plecanatide, compared with placebo (P less than .001).
Patients on 3.0 mg of plecanatide had the highest percentage of treatment-emergent adverse events (106 patients or 44.7%), compared with 1.0 mg of plecanatide (103 patients or 43.3%), 0.3 mg (99 or 31.8%), and placebo (96 or 40.7%).
The most common adverse event on the drug was diarrhea (9.7% on 3.0 mg of plecanatide vs. 1.3% on placebo). Seven patients (3%) on 3.0 mg of plecanatide withdrew due to diarrhea, compared with eight patients (3.4%) on 1.0 mg of plecanatide, two patients (0.8%) on 0.3 mg, and 1 patient (0.4%) in the placebo group.
Other adverse events included flatulence, abdominal pain, abdominal distention, nausea, nasopharyngitis, urinary tract infection, and headache. Serious adverse events, which were considered unrelated to the treatment, included noncardiac chest pain (1 patient on 0.3 mg of plecanatide), endometriosis (1 patient on 1.0 mg), and acute cholecystitis and hypoaesthesia with weakness (2 patients on 3.0 mg). Five patients in the placebo group experienced hypertension exacerbation, gastroenteritis, spontaneous abortion, atypical chest pain, and asthma exacerbation. Dr. Miner said he could not share the bloating data at the time of his presentation.
Dr. Gerson said that the ideal drug would "relieve constipation and other symptoms, but doesn’t have a lot of side effects. It’ll be nice to have a drug that is better tolerated than what’s available out there."
Synergy is preparing a clinical study report for submission to the Food and Drug Administration. It is presenting additional data in upcoming scientific meetings in 2013, according to a company news release.
The FDA approved linaclotide (Linzess) in August 2012 for treatment of CIC and IBS-C. Linaclotide, also a guanylate cyclase C agonist, is comarketed by Ironwood Pharmaceuticals and Forest Pharmaceuticals.
Dr. Miner is a consultant and has done research for Ventrus Biosciences and Synergy Pharmaceuticals. Dr. Gerson had no disclosures.
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