Trulance improves symptoms in patients with IBS-C

CHICAGO — Trulance safely and effectively improved symptoms in patients with constipation-predominant irritable bowel syndrome, according to the results of two phase 3 clinical trials presented at Digestive Disease Week.

IBS-C “represents a significant medical burden. It’s estimated that 5% of adults in the U.S. population are affected,” Ronald Fogel, MD, of the Clinical Research Institute of Michigan, said during his presentation. “Many patients report being little or not at all satisfied with the effect of current therapies, and in addition to an inadequate treatment response, some patients experience adverse events,” as well as a significant socioeconomic burden, including increased health care costs and missed days of work or school.

Trulance (plecanatide, Synergy Pharmaceuticals) is an orally-active peptide that replicates the function of uroguanylin, a guanylate cyclase-C receptor agonist, which stimulates fluid secretion and promotes stool consistency. It was recently approved by the FDA for the treatment of chronic idiopathic constipation and the company has submitted an sNDA for the treatment of IBS-C.

Fogel presented data on two identically designed double blind trials involving a 2-week pre-treatment period, a 12-week treatment period and a 2-week follow-up period. The investigators enrolled 1,055 patients (76.4% women) into the first trial and 1,135 (71.8%) patients into the second trial. All patients had IBS-C.

They then randomly assigned patients to receive either 3 mg or 6 mg plecanatide or placebo once daily with or without food.

Fogel noted that “25% of the study participants were male, a larger number than has been reported in other studies.”

Both doses of plecanatide met the primary endpoint in both studies. There were significantly more overall responders — defined by the FDA as patients with at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement from baseline — in the same week, for at least half of the 12 treatment weeks.

In the first study, 30.2% of the 3-mg group and 29.5% of the 6-mg group were overall responders compared with 17.8% of the placebo group (P < .001 for both). In the second study the proportions were 21.5% and 24% vs. 14.2% (P = .009 and P < .001, respectively).

Both doses of plecanatide were also significantly more effective than placebo in improving stool frequency and abdominal pain endpoints individually.

Regarding the timing of treatment effect, there was “a response in the first week of treatment that appeared to increase and reached the maximum around week 6, and then persisted until the drug was discontinued at week 12, and then the effect of plecanatide gradually dissipated,” Fogel said.

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There were significantly more overall responders for 2 of the last 4 weeks of treatment in the plecanatide groups, so “plecanatide was better than placebo at producing a sustained efficacy response,” he added.

The studies confirmed the drug’s established safety and tolerability profile, as the only treatment-emergent adverse event occurring in more than 2% of patients and at an incidence greater than placebo was diarrhea (4% of the two plecanatide groups vs. 1% of the placebo group), Fogel said.

Severe diarrhea was reported in 1% and 0.4% of patients in the 3 mg and 6 mg plecanatide groups, respectively, and in 0.1% of the placebo group.

Few patients discontinued treatment due to adverse events, with 3.1% of the 3-mg, 2.3% of the 6-mg group and 0.8% of the placebo group withdrawing in the first study, and 1.9%, 2.1% and 0%, respectively, withdrawing in the second study. Further, few patients stopped treatment due to diarrhea (1.7%, 1.2% and 0% in the first study and 0.8%, 1.6% and 0% in the second, respectively).

Non–GI-related serious treatment-emergent adverse events occurred in 1% of the first study and in 0.5% of the second study, and there was little difference between treatment groups. There was no incidence of dehydration.

“Plecanatide was efficacious, safe and had a low rate of diarrhea in adult patients with IBS-C,” Fogel concluded. “Plecanatide treatment had a low rate of adverse events including diarrhea, which led to a low rate of discontinuation due to diarrhea.”

The drug is currently under review by the FDA for the treatment of IBS-C in adults, he said. – by Adam Leitenberger

Reference:

Fogel R, et al. Abstract #874k. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.

Disclosures: Fogel reports no relevant financial disclosures.