Safety and tolerability of plecanatide in patients with chronic idiopathic constipation: long-term evidence from an open-label study

Abstract

Objective: This multi-center, fixed-dose, open-label study evaluated the long-term safety and tolerability of once-daily oral plecanatide for the treatment of adults with chronic idiopathic constipation (CIC).

Methods: Eligible patients completed a phase 2b or phase 3 double-blind study of plecanatide, or had not previously been treated with plecanatide. Enrolled patients received plecanatide (3 or 6 mg) for up to 72 weeks. Safety and tolerability were assessed by the incidence, nature, and severity of spontaneously reported treatment-emergent adverse events (TEAEs). Patients also completed Patient Global Assessment questionnaires, which included measures of treatment satisfaction and the desire to continue treatment.

Results: There were 2370 patient exposures in this study, with the vast majority (90.5%) receiving treatment with plecanatide 6 mg. At the time of study closure, 1932 (81.5%) had completed or were still receiving study drug. TEAEs were qualitatively and quantitatively similar to those observed in prior double-blind studies. The most common TEAEs were diarrhea (7.1%) and urinary tract infection (2.2%). TEAEs leading to discontinuation occurred in 5.3% of patients, with diarrhea leading to discontinuation in 3.1%. Most TEAEs were mild/moderate in severity and were generally considered not related to plecanatide treatment. At the end of treatment, the median score for treatment satisfaction was 4.0 (quite satisfied), and the median score for treatment continuation was 4.0 (quite likely).

Conclusions: Long-term treatment of adults with CIC demonstrated that plecanatide was safe and well tolerated, with low TEAE and discontinuation rates. Patients indicated satisfaction and a desire to continue with plecanatide treatment.

Keywords:

• Chronic idiopathic constipation
• functional constipation
• plecanatide
• uroguanylin
• long-term
• safety
• tolerability

Transparency

Declaration of funding

Funding for these trials and editorial support were provided by Synergy Pharmaceuticals Inc., who also provided the plecanatide used for the study.

Declaration of financial/other relationships

CFB has participated in studies with plecanatide and was paid by Synergy Pharmaceuticals Inc. as a principal investigator. PG is an employee and stock holder of Synergy Pharmaceuticals Inc. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Writing and editorial support were provided by Ann Sherwood, PhD, Nicole Coolbaugh, and Philip Sjostedt, BPharm, of The Medicine Group, LLC (New Hope, PA). ClinicalTrials.gov Registration Identifier: NCT01919697.