Abstract

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

Clin Ther. 2022 Jan 24;S0149-2918(21)00462-8. doi: 10.1016/j.clinthera.2021.11.009.Online ahead of print.

Baharak Moshiree 1, Philip Schoenfeld 2, Howard Franklin 3, Ali Rezaie 4

 
     

Author information

1Division of Gastroenterology, Hepatology, and Nutrition, Atrium Health, Charlotte, North Carolina. Electronic address: Baha.moshiree@atriumhealth.org.

2John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan.

3Salix Pharmaceuticals Inc, Bridgewater, New Jersey.

4Cedars-Sinai Medical Center, Los Angeles, California.

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.

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