Clinical Trials

Date: 2017-02-27

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in the American Journal of Gastroenterology

Company: Synergy Pharmaceuticals (USA - NY)

Product: Trulance™ (plecanatide)

Action mechanism: peptide/oral guanylate cyclase C agonist.  Plecanatide is an analogue of uroguanylin, with the exception of a single amino acid. Uroguanylin is a naturally occurring and endogenous human GI peptide. Uroguanylin is thought to act in a pH-sensitive manner, targeting GC-C receptors primarily in the small intestine coinciding with areas of fluid secretion. Plecanatide activates these receptors found on the GI mucosal epithelial cells, leading to secretion of fluid, facilitating bowel movements.

Disease: chronic idiopathic constipation (CIC)

Therapeutic area: Digestive diseases - Gastrointestinal diseases - Inflammatory diseases

Country:

Trial details:

Latest news:

• • On February 27, 2017, Synergy Pharmaceuticals announced that the American Journal of Gastroenterology has published detailed results from a pivotal Phase 3 trial that demonstrated the efficacy and safety of Trulance™ (plecanatide) for the treatment of adults with chronic idiopathic constipation (CIC).
• • On October 17, 2016, Synergy Pharmaceuticals presented new long-term safety data of plecanatide, currently being evaluated by the FDA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. These data, which were presented at the American College of Gastroenterology (ACG) annual scientific meeting, showed that plecanatide was associated with low adverse events and low discontinuation rates in patients with CIC who received plecanatide (3 mg or 6 mg) once-daily for up to 72 weeks.
• In this long-term study, which evaluated 2,370 patients, the most common adverse events in both dose groups were diarrhea (7.1%) and urinary tract infection (2.2%). The remainder of adverse events occurred in less than 2% of patients treated with plecanatide. Adverse events leading to discontinuation occurred in 5.3% of patients treated with plecanatide, with discontinuation due to diarrhea occurring in 3.1% of patients. In addition, this study asked patients about level of treatment satisfaction and desire to continue treatment. The median score for treatment satisfaction was 4.0 (4=quite satisfied) and for continuation of treatment was 4.0 (4=quite likely).
• Synergy also presented plecanatide data from an integrated efficacy and safety analysis which are consistent with findings of two previously presented double-blind, placebo-controlled Phase 3 trials that evaluated more than 2,600 patients with CIC over a 12-week treatment period. These additional analyses confirmed a significantly greater response rate of durable overall complete spontaneous bowel movements (CSBM) in each of the two plecanatide dose groups (3 mg, 20.5%; 6 mg, 19.8%) when compared to the placebo group (11.5%, p<0.001 for both doses). These significant increases in CSBMs with both plecanatide dose groups were seen as early as the first week and maintained through the treatment period compared with placebo. Results at 12 weeks also found:
• Secondary endpoints (stool consistency, straining and bloating) were significantly improved compared to placebo. Adverse event rates were similar across plecanatide-treatment groups and placebo (30.6% in 3 mg and 31.1% in 6 mg dose groups compared to 28.7% in placebo), Diarrhea was the most common adverse event (4.6% in 3 mg and 5.1% in 6 mg compared to 1.3% in placebo). Discontinuation rates were low across all treatment groups (3 mg, 4.1%; 6 mg, 4.5%; and placebo, 2.2%).
• In addition, Synergy has already completed patient recruitment for the two double-blind, placebo-controlled Phase 3 clinical trials with plecanatide in IBS-C and remains on-track to report top-line data from both trials in the fourth quarter of this year.
• • On May 21, 2016, Synergy Pharmaceuticals announced  additional data from two pivotal phase 3 clinical trials (Study-00 and Study-03) evaluating the efficacy and safety of plecanatid in treating patients with chronic idiopathic constipation (CIC). Data were presented at Digestive Disease Week (DDW) in San Diego.
• The primary endpoint for both pivotal trials was the durable overall complete spontaneous bowel movement (CSBM) responder endpoint, as defined by the FDA. As previously disclosed, both plecanatide 3 mg and 6 mg doses met the primary endpoint and demonstrated statistical significance in the proportion of patients in the intention-to-treat population who were durable overall CSBM responders compared to placebo during the 12-week treatment period (21.0% in 3 mg and 19.5% in 6 mg dose groups compared to 10.2% in the placebo group; p<0.001 for both doses in Study-00 and 20.1% in 3 mg and 20.0% in 6 mg dose groups compared to 12.8% in the placebo group; p=0.004 for both doses in Study-03). The most common adverse event (AE) was diarrhea (5.9% in 3 mg and 5.7% in 6 mg dose groups compared to 1.3% in the placebo group for Study-00 and 3.2% in 3 mg and 4.5% in 6 mg dose groups compared to 1.3% in the placebo group in Study-03).

Is general: Yes