Prucalopride in the treatment of chronic constipation in patients from the Asia‐Pacific region: a randomized, double‐blind, placebo‐controlled study

Abstract

BackgroundThe study evaluated efficacy and safety of the 2 mg dose of prucalopride compared to placebo in patients with chronic constipation (CC) from the Asia-Pacific region.MethodsRandomized, placebo-controlled, parallel-group, phase III study with 2-week run-in, 12-week treatment phase, and 1-week follow-up. Adult patients with CC (≤2 spontaneous bowel movements per week) received 2 mg prucalopride or placebo, once-daily, for 12 weeks. Primary efficacy measure was percentage of patients with average of ≥3 spontaneous complete bowel movements (SCBMs) per week (Responders) during the 12-week treatment. A key secondary endpoint was Responders during first 4 weeks of treatment. Other efficacy assessments were based on patient diaries, their assessments of symptoms and quality of life, and investigator’s assessment on efficacy of treatment. Safety assessments included adverse events, laboratory values, and cardiovascular events.Key ResultsEfficacy and safety were evaluated for 501 patients who received study drug. On the primary endpoint, prucalopride was significantly more effective than placebo with 83 (33.3%) vs 26 (10.3%) patients having a weekly average of ≥3 SCBMs during the 12-week treatment (P < 0.001). Respective percentages were 34.5%vs 11.1% over first 4 weeks (P < 0.001). On other secondary endpoints, clinical improvement was generally larger and statistically superior (P < 0.001) in the prucalopride group. Most frequently reported adverse events were diarrhea, nausea, abdominal pain, and headache.Conclusion & InferencesPrucalopride 2 mg given once-daily significantly improved bowel function, associated symptoms, and satisfaction in CC over a 12-week treatment period, and was safe and well tolerated by patients in the Asia-Pacific region.

ThePAC‐SYMquestionnaire for chronic constipation: defining the minimal important difference

“…This analysis used integrated data from six phase 3 and 4, multicentre, double‐blind, randomised, placebo‐controlled, parallel‐group trials of the efficacy and safety of prucalopride in patients with chronic constipation, performed across three continents (Table 1; ClinicalTrials.gov identifiers: SPD555‐302 [NCT01147926], SPD555‐401 [NCT01424228], PRU‐CRC‐3001 [NCT01116206], PRU‐USA‐13 [NCT00485940], PRU‐USA‐11 [NCT00483886] and PRU‐INT‐6 [NCT00488137]) 11, 23, 24, 25, 26, 27. The designs of these trials were similar and have been described in detail previously 11, 23, 24, 25, 26, 27…”

“…The designs of these trials were similar and have been described in detail previously 11, 23, 24, 25, 26, 27…”

Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea, 2015 Revised Edition

“…153 Prucalopride, 2 mg once-daily treatment over 12 weeks, was more efficacious than a placebo in improving stool frequency and stool consistency, decreasing the need for rescue medications, reducing the symptoms of constipation in Asian and non-Asian women, and was found to be safe and well-tolerated. [154][155][156][157][158] In addition, in elderly patients, prucalopride has beneficial effects on bowel movements and constipation-associated symptoms. 159 Satisfaction with bowel function was maintained for up to 18 months of treatment with prucalopride.…”

Use of Prucalopride for Chronic Constipation: A Systematic Review and Meta-analysis of Published Randomized, Controlled Trials

“…Sixteen randomized, controlled trials [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] on 3943 patients were retrieved from the search of standard medical electronic databases. The characteristics, salient features and treatment protocols adopted in the included randomized, controlled trials are given in the Table. All trials were adequately randomized using either computer generated sequential pattern or other reliable random pattern methods.…”