A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy, Safety, and Tolerability of Prucalopride in Men With Chronic Constipation

Abstract

OBJECTIVES:Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation.METHODS:This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation—Symptoms (PAC-SYM) and Patient Assessment of Constipation—Quality of Life (PAC-QOL) questionnaires.RESULTS:In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as “quite a bit” to “extremely” effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated.CONCLUSIONS:Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.

The PAC‐SYM questionnaire 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…”

“…As such, the questionnaire is increasingly being used as a patient‐reported outcome measure in clinical trials of constipation. Over 18 clinical studies have used the PAC‐SYM, since its validation in 1999: 14 of these have been reported since 2010 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Moreover, these trials have examined a range of interventions including sacral nerve stimulation,20 lifestyle changes19 and pharmacological agents 6, 11…”

Treatment of gastrointestinal autonomic neuropathy

“…Interestingly, other symptoms associated with constipation, such as bloating, discomfort, a sensation of incomplete bowel movement and excessive straining, have the potential to be improved by treatment [25]. Recent data also support its use in men [26].…”

Prukalopride in the Treatment of Chronic Constipation

“…Одни пациенты (47% принимав-ших прукалоприд против 30,4% -пла-цебо, p < 0,0001) оценивают лечение как эффективное, а другие пациенты (53% принимавших прукалоприд про-тив 39% -плацебо, p = 0,0035) значи-тельно чаще отмечали улучшение по шкалам PAC-QоL [43].…”