Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis

Anton Emmanuel, Marina Cools, Lieve Vandeplassche, René Kerstens, Anton Emmanuel, Marina Cools, Lieve Vandeplassche, René Kerstens

Abstract

Objectives: Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.

Methods: This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813; and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at the start and end (4 or 12 weeks) of treatment. At these visits, patients assessed the presence and severity of their symptoms.

Results: In total, 280 patients had CTT measurements before and at the end of treatment and were included in the analysis. Their mean age was 43 years, 93% were women, and mean duration of constipation was 19 years. After a once daily treatment with prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95% confidence interval (CI): -18.9, -5.1) and 13.9 h (95% CI: -20.5, -7.4), respectively; CTT increased by 0.5 h (95% CI: -4.5, 5.5) with placebo (n=112). At the end of the trial, symptoms including bloating/flatulence/distension and straining were rated as severe or very severe by a higher proportion of patients with slow or very slow CTT (>48 h) than by those with normal CTT.

Conclusions: There was a clear relationship between increased CTT and increased symptom severity in patients with chronic constipation. Treatment with prucalopride accelerated CTT in these individuals.

Figures

Figure 1
Figure 1
Change in CTT from before treatment to the end of treatment with placebo, prucalopride 2 mg, or prucalopride 4 mg in (a) all patients and (b) patients with slow or very slow CTTs (>48 h) at baseline. **P<0.001 vs. baseline; two-sample t-test. Data are shown as mean±95% confidence intervals. CTT, colonic transit time.
Figure 2
Figure 2
(a) Proportion of responders and (b) mean colonic transit times in responders and nonresponders after treatment with placebo, prucalopride 2 mg, or prucalopride 4 mg. ††P<0.001 vs. placebo; ‡P<0.05 vs. nonresponders calculated using the paired t-tests. Numbers in each bar indicate the number of patients in each group.
Figure 3
Figure 3
Relationship between CTTs at the end of treatment and the proportion of patients with severe or very severe constipation-related symptoms. Normal CTT n=84; slow CTT n=150; very slow CTT n=46. CTT, colonic transit time.
Figure 4
Figure 4
Proportion of bowel movements with (a) hard/very hard consistency or (b) normal consistency in patients with normal and slow CTTs at the end of treatment. Data are shown as mean±95% confidence intervals. CTT, colonic transit time.

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