The Effect of Acid Suppression Therapy on the Safety and Efficacy of Plecanatide: Analysis of Randomized Phase III Trials

Abstract

Purpose: Plecanatide, an approved therapy for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation, is an analogue of uroguanylin that replicates its pH-sensitive activity and binds to guanylate cyclase-C receptors expressed on intestinal epithelium, stimulating fluid secretion. This analysis explores concomitant acid suppression therapy's effect on the efficacy and safety of plecanatide in adults with CIC.

Methods: Data from 2 placebo-controlled, 12-week Phase III trials of plecanatide in CIC were pooled. Patients were randomized to receive placebo, plecanatide 3 mg, or plecanatide 6 mg. The primary endpoint was the durable, overall complete spontaneous bowel movement (CSBM) response rate (defined as ≥3 CSBMs in a given week and ≥1 CSBM increase from baseline within a week for ≥9 of 12 weeks, including ≥3 of the last 4 treatment weeks). Safety was also evaluated. Results were stratified by concomitant use or nonuse of acid suppression therapy.

Findings: Of the pooled intent-to-treat population, 338 of 2639 patients (12.8%) received concomitant acid suppression medication. Efficacy response rates in patients using acid suppressors were 23.6% with plecanatide 3 mg (P = 0.001 vs placebo), 22.1% with plecanatide 6 mg (P = 0.002), and 7.6% with placebo. Responses were similar in patients not using acid suppressors: 20.4% (plecanatide 3 mg, P < 0.001), 19.6% (plecanatide 6 mg, P < 0.001), and 12.1% (placebo). Serious adverse events were experienced by 3.3% of patients who used concomitant acid suppression and 1.0% of those who did not.

Implications: Plecanatide treatment is safe and efficacious for patients with CIC when administered with concomitant acid suppression medication.

Clinicaltrials: gov identifiers: NCT02122471 and NCT01982240.

Keywords: constipation; functional gastrointestinal diseases; irritable bowel syndrome; plecanatide.

Conflict of interest statement

Disclosure B. Moshiree has been a consultant for or participated in advisory boards for Allergan/Ironwood Pharmaceuticals, Takeda, Progenity, Medtronic, Alfasigma, Alnylam, Nestle Science Institute, QOL Medical, and Salix Pharmaceuticals, and has received grant support from Medtronic and Prometheus Lab. P. Schoenfeld has been a consultant and advisory board member for Salix Pharmaceuticals, Allergan/Ironwood Pharmaceuticals, Phathom Pharmaceuticals, and Takeda Pharmaceuticals, and has received honoraria from Salix Pharmaceuticals, Allergan/Ironwood Pharmaceuticals, and Alnylam Pharmaceuticals. H. Franklin is an employee of Salix Pharmaceuticals. A. Rezaie reports support for research and consultation from Salix Pharmaceuticals, Bayer, and Synergy Pharmaceuticals. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

Published by Elsevier Inc.