Clinical Trials

Date: 2017-05-09

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the Digestive Disease Week (DDW) 2017

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: irritable bowel syndrome with constipation (IBS-C)

Therapeutic area: Digestive diseases - Gastrointestinal diseases - Inflammatory diseases

Country: USA

Trial details:

• The plecanatide phase 3 IBS-C program includes two randomized, 12-week, double-blind, placebo-controlled trials evaluating the efficacy and safety of plecanatide treatment (3 mg and 6 mg doses), taken as a tablet once-a-day in patients with irritable bowel syndrome with constipation. Both trials included a two-week pre-treatment baseline period, a 12-week treatment period, and a two-week post-treatment follow-up period. The phase 3 IBS-C program was conducted in North America and designed to support regulatory submission in the U.S. Patients who were enrolled in these trials fulfilled Rome III IBS-C criteria related to abdominal pain and stool changes.
• The first phase 3 IBS-C trial assessed 1,135 patients (28.2% males and 71.8% females) that were randomly assigned to take 3 mg or 6 mg plecanatide or placebo once-a-day during the 12-week treatment period (377 patients in the 3 mg dose group, 379 patients in the 6 mg dose group and 379 patients in the placebo group).
• The second phase 3 IBS-C trial assessed 1,054 patients (23.6% males and 76.4% females) that were randomly assigned to take 3 mg or 6 mg plecanatide or placebo once-a-day during the 12-week treatment period (351 patients in the 3 mg dose group, 349 patients in the 6 mg dose group and 354 patients in the placebo group).
• The primary endpoint for both trials is the percentage of patients who are Overall Responders (%) during the 12-week treatment period. An Overall Responder, as defined by the FDA, is a patient who fulfills both ? 30% reduction in worst abdominal pain and an increase of ? 1 complete spontaneous bowel movement (CSBM) from baseline, in the same week, for at least 50% of the 12 treatment weeks. The Overall Responder endpoint is the current regulatory endpoint required for U.S. approval in IBS-C.

Latest news:

• • On May 9, 2017, Synergy Pharmaceuticals announced that the company will present late-breaking data from Phase 3 studies evaluating Trulance™ (plecanatide) for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) at Digestive Disease Week (DDW), in Chicago.
• In two large Phase 3 studies of more than 2,100 total patients with IBS-C, Trulance™ 3 mg and 6 mg doses met the primary endpoint showing statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period (Study 1: 30.2% in 3 mg and 29.5% in 6 mg dose groups compared to 17.8% in placebo; p<0.001 for 3 mg and p<0.001 for 6 mg; Study 2: 21.5% in 3 mg and 24.0% in 6 mg dose groups compared to 14.2% in placebo; p=0.009 for 3 mg and p<0.001 for 6 mg).
• In a pooled analysis of both studies, a statistically significant percentage of patients treated with Trulance™ achieved at least a 30 percent reduction in abdominal intensity pain compared to placebo for at least six weeks of the 12-week treatment period (36.8% in 3 mg and 39.1% in 6 mg dose groups compared to 27.3% in placebo; p<0.001). A statistically significant percentage of patients treated with Trulance™ also saw improvement in stool frequency compared to placebo for at least six weeks of the 12-week treatment period, as measured by an increase in at least one CSBM per week from baseline (40.9% in 3 mg and 41.9% in 6 mg dose groups compared to 31.4% in placebo; p<0.001).
• In both studies, treatment with Trulance™ also resulted in a significantly greater percentage of sustained efficacy responders, as measured by patients who were Overall Responders in the last two of four weeks of treatment (24.3% in 3 mg and 25.5% in 6 mg dose groups compared to 15.6% in placebo; p<0.001).
• In both studies, the most common adverse event was diarrhea (4.3% at 3 mg and 4.0% at 6 mg compared to 1.0% for placebo), with severe diarrhea rates that were low across both groups in both studies (1.0% at 3 mg and 0.4% at 6 mg, compared to 0.1% for placebo). Discontinuation rates were low across both groups and discontinuations due to diarrhea were infrequent (1.2% at 3 mg and 1.4% at 6 mg compared to no patients for placebo).
• • On December 22, 2016, Synergy Pharmaceuticals announced results from the second of two pivotal phase 3 clinical trials evaluating the efficacy and safety of plecanatide in 1,054 adult patients with irritable bowel syndrome with constipation. Preliminary analysis of the data indicates that both plecanatide 3 mg and 6 mg doses met the study’s primary endpoint and showed statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period (30.2% in 3 mg and 29.5% in 6 mg dose groups compared to 17.8% in placebo; p<0.001 for 3 mg and p<0.001 for 6 mg).
• The most common adverse event was diarrhea which occurred in 5.4% of patients in 3 mg and 4.3% of patients in 6 mg dose groups compared to 0.6% of placebo-treated patients. Ten patients in the trial (<1.0%) experienced serious adverse events but there was no imbalance across treatment groups in either incidences or individual serious adverse events. Overall, the rates of withdrawal from treatment because of an adverse event were low (2.6% in 3 mg and 2.3% in 6 mg dose groups compared to 0.8% in placebo) and discontinuations due to diarrhea were infrequent (1.7% in 3 mg and 1.2% in 6 mg dose groups compared to 0 in placebo).
• • On December 9, 2016, Synergy Pharmaceuticals announced positive top-line results from the first of two pivotal phase 3 clinical trials evaluating the efficacy and safety of plecanatide in 1,135 adult patients with irritable bowel syndrome with constipation. Preliminary analysis of the data indicates that both plecanatide 3 mg and 6 mg doses met the study’s primary endpoint and showed statistical significance in the percentage of patients who were Overall Responders compared to placebo during the 12-week treatment period (21.5% in 3 mg and 24.0% in 6 mg dose groups compared to 14.2% in placebo; p=0.009 for 3 mg and p<0.001 for 6 mg).
• The most common adverse event was diarrhea which occurred in 3.2% of patients in 3 mg and 3.7% of patients in 6 mg dose groups compared to 1.3% of placebo-treated patients. Four patients in the trial (0.4%) experienced serious adverse events but there was no imbalance across treatment groups in either incidences or individual serious adverse events. Overall, the rates of withdrawal from treatment because of an adverse event were low (1.9% in 3 mg and 1.8% in 6 mg dose groups compared to 0 in placebo) and discontinuations due to diarrhea were infrequent (0.8% in 3 mg and 1.6% in 6 mg dose groups compared to 0 in placebo).

Is general: Yes