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Constipation Drug Plecanatide Succeeds in Phase III Trial
Positive results have been reported from the first of two pivotal phase III studies evaluating the efficacy and safety of two doses of plecanatide (Synergy Pharmaceuticals) –– 3 mg and 6 mg, taken as a once-daily tablet –– in 1,346 adult patients with chronic idiopathic constipation (CIC).
A preliminary analysis of the data indicated that both plecanatide doses met the study’s primary endpoint and demonstrated statistical significance in the proportion of patients in the intention-to-treat population who were durable overall responders compared with placebo during the 12-week treatment period (21.0% in the 3-mg group and 19.5% in the 6-mg compared with 10.2% in the placebo group; P < 0.001 for both doses).
Plecanatide was safe and well tolerated at both doses; the most common adverse event was diarrhea, which occurred in 5.9% of patients in the 3-mg group and in 5.5% of patients in the 6-mg group compared with 1.3% of the placebo group.
Stool consistency was the study’s key secondary endpoint. Both the 3-mg and 6-mg doses of plecanatide showed statistically significant improvements from baseline in Bristol Stool Form Scale (BSFS) scores compared with placebo (mean increases of 1.53 in the 3-mg group and 1.52 in the 6-mg group compared with a mean increase of 0.77 in the placebo group; P < 0.001 for both doses). The observed improvements began at week 1 continued throughout the 12-week treatment period and returned towards baseline, with no indication of an exaggerated or rebound effect, following discontinuation of treatment.
Fifteen patients in the trial (1.1%) experienced serious adverse events (AEs), but there was no imbalance across treatment groups in either incidences or individual serious AEs. Overall, the rates of withdrawal from treatment because of an AE were low (5.1 % in the 3-mg group and 5% in the 6-mg group compared with 1.3% in the placebo group), and discontinuations due to diarrhea were infrequent (2.7% in the 3-mg group and 2.4% in 6-mg group compared with 0.4% in the placebo group).
A new drug application (NDA) for plecanatide in the CIC indication is expected to be filed with the FDA in the fourth quarter of 2015.
Plecanatide is a uroguanylin analogue. Uroguanylin is a naturally occurring gastrointestinal (GI) peptide produced by humans in the small intestine and plays a key role in regulating normal GI activity. Orally administered plecanatide is designed to mimic uroguanylin’s natural activity and to regulate the movement of fluid required for normal digestion.
Source: Synergy Pharmaceuticals; June 17, 2015.