Effects of treatment cessation and re‐treatment in randomized controlled trials of prucalopride in patients with chronic idiopathic constipation

• Published in: Neurogastroenterology and motility 2023-07, Vol.35 (7), p.e14563-n/a
• Main Authors: Hinson, Jimmy, Achenbach, Heinrich, Terreri, Brian, Boules, Mena
• Format: Article
• Language: English
• Subjects: Adult; chronic constipation; Chronic Disease; Clinical trials; Constipation; Constipation - drug therapy; Double-Blind Method; efficacy; Humans; Patients; Placebos; prucalopride; Randomized Controlled Trials as Topic; re‐treatment; safety; Treatment Outcome; Withholding Treatment
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.14563

Background Prucalopride is a selective, high‐affinity serotonin type 4 receptor agonist approved for the treatment of chronic idiopathic constipation (CIC) in adults. We investigated the impact of prucalopride cessation and re‐treatment on efficacy and safety. Methods Data were from two randomized controlled trials in adults with CIC. In a dose‐finding trial, complete spontaneous bowel movements (CSBMs) and treatment‐emergent adverse events (TEAEs) were assessed during a 4‐week run‐out period after a 4‐week treatment period (TP; prucalopride 0.5–4 mg once daily or placebo). In a re‐treatment trial, CSBMs and TEAEs were assessed during two 4‐week TPs (prucalopride 4 mg once daily or placebo) separated by a 2‐ or 4‐week washout period. Key Results In the dose‐finding trial (N = 234; 43–48 patients/group), mean CSBMs/week and the proportion of responders (≥3 CSBMs/week) were higher with prucalopride than placebo during the TP, but similar in all groups 1–4 weeks after treatment cessation. TEAEs were less frequent following treatment cessation. In the re‐treatment trial (efficacy analyses: prucalopride, n = 189; placebo, n = 205), the proportion of responders was similar in both TPs and significantly higher (p ≤ 0.001) with prucalopride (TP1, 38.6%; TP2, 36.0%) than placebo (TP1, 10.7%; TP2, 11.2%). Most patients who responded to prucalopride in TP1 responded again in TP2 (71.2%). TEAEs were less frequent in TP2 than TP1. Conclusions and Inferences Prucalopride cessation resulted in a loss of clinical effect to baseline levels within 7 days. Similar efficacy and safety were observed between TP1 and TP2 after prucalopride was re‐initiated following a washout period. Cessation of prucalopride therapy resulted in a loss of initial clinical effect in a large proportion of patients with chronic idiopathic constipation. However, re‐treatment with prucalopride after a period of treatment interruption provided a clinical response similar to that of the initial course of therapy.