Digestive Diseases and Sciences

, Volume 58, Issue 9, pp 2580–2586

Plecanatide, an Oral Guanylate Cyclase C Agonist Acting Locally in the Gastrointestinal Tract, Is Safe and Well-Tolerated in Single Doses


    • Synergy Pharmaceuticals, Inc.
  • Stephen Comiskey
    • Synergy Pharmaceuticals, Inc.
  • John A. Foss
    • Synergy Pharmaceuticals, Inc.
  • Rong Feng
    • Synergy Pharmaceuticals, Inc.
  • Laura Barrow
    • Synergy Pharmaceuticals, Inc.
  • Gail M. Comer
    • Synergy Pharmaceuticals, Inc.
  • Gary S. Jacob
    • Synergy Pharmaceuticals, Inc.
Original Article

DOI: 10.1007/s10620-013-2684-z

Cite this article as:
Shailubhai, K., Comiskey, S., Foss, J.A. et al. Dig Dis Sci (2013) 58: 2580. doi:10.1007/s10620-013-2684-z



Plecanatide, an analogue of uroguanylin, activates the guanylate cyclase C (GC-C) receptor found on the GI mucosal epithelial cells, leading to secretion of fluid, facilitating bowel movements. Plecanatide is being investigated as a potential treatment for constipating GI disorders. The aim of this investigation was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single doses of plecanatide in healthy volunteers.


A total of 72 healthy volunteers at a single site were randomized in 9 cohorts to receive oral plecanatide or placebo from 0.1 to 48.6 mg. Plasma PK samples were collected pre-dose and post-dose. PD assessments included time to first stool, stool frequency, and stool consistency using the Bristol Stool Form Scale. All adverse events were documented.


Plecanatide was safe and well-tolerated at all dose levels. A total of 17 of 71 subjects (23.9 %) reported 25 treatment-emergent adverse events (TEAEs) during the study. The number of TEAEs reported by subjects who received plecanatide or placebo was comparable (24.5 vs. 22.2 %, respectively). There were no dose-related increases in TEAEs or any SAEs reported. No measurable systemic absorption of oral plecanatide was observed at any of the oral doses studied, utilizing an assay sensitive down to 1 ng/mL.


Plecanatide, an oral GC-C agonist, acting locally within the GI tract without measurable systemic exposure, was safe and well-tolerated in single doses up to 48.6 mg. The study was not powered for statistical analyses, but trends in PD parameters supported continued clinical development.


Guanylate cyclase C (GC-C)Cystic fibrosis transmembrane conductance regulator (CFTR)Gastrointestinal (GI)Uroguanylin (UG)Cyclic GMP (cGMP)Chronic functional constipation (CC)Irritable bowel syndrome-constipation predominant (IBS-C)

Copyright information

© Springer Science+Business Media New York 2013