Su2061 Relationship Between Colonic Transit Time and Symptoms of Constipation: Integrated Results From Clinical Trials of Prucalopride

Abstract

Introduction: In patients with chronic constipation (CC), treatment with the selective, highaffinity 5-HT4 receptor agonist prucalopride is associated with improvements in colonic transit time (CTT) that correlate with bowel movement frequency. The aim of this analysis was to assess the relationship between CTT and gastrointestinal symptoms in relation to prucalopride use. Methods: An integrated analysis was conducted of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with CC. CC was defined as ≤3 spontaneous complete bowel movements per week as well as straining, sensation of incomplete evacuation, or hard stools for ≥25% of stools. Patients with secondary constipation were excluded. CTT was assessed at pre-selected study sites at the start and end of treatment, using radio-opaque markers, when the patients were not taking laxatives. Slow CTT was defined as ≥48 hours and very slow CTT as ≥96 hours. At every visit, patients assessed the presence and severity of their symptoms (absent, very mild, mild, moderate, marked, severe and very severe). Results: Overall, 280 patients had CTT assessments at both baseline and final visit and were included in this analysis. Of these, 112 were treated with placebo, 98 with prucalopride 2mg and 70 with prucalopride 4mg. Average patient age was 43 years; average duration of constipation was 19 years; and 93% of patients were female. Overall, mean baseline CTT was 66 hours (range: 2-144 hours) and 70% of patients (n = 196) had slow CTT. After treatment with prucalopride 2mg and 4mg, CTT was reduced by 12 hours (95% confidence interval [CI]: -18.9, -5.1) and 14 hours (CI: -20.5, -7.4), respectively; CTT increased by 0.5 hours (CI: -4.5, +5.5) with placebo. Of patients with slow CTT at baseline, 16%, 68% and 65% had normal CTT after treatment with placebo, prucalopride 2mg and prucalopride 4mg, respectively. A higher proportion of patients with slow or very slow CTT at the end of the study had severe/very severe abdominal pain/cramps, straining symptoms or unproductive calls to defecate, compared with patients with normal CTT (Figure 1). Severe/very severe urgency was less common in the slow and very slow CTT groups than in patients with normal CTT. For other symptoms such as fatigue, abdominal bloating, flatulence and distension, a relationship with CTT was less clear. Conclusions: This study is the first to show a relationship between idiopathic slow CTT and symptom severity in patients with CC. Slower CTT is associated with a greater need to strain, unproductive calls to defecate and abdominal pain/cramps. Figure 1. Relationship between transit time at the end of treatment and the proportion of patients with severe or very severe symptoms for (A) abdominal pain/cramps and straining and (B) unproductive calls to defecate and urgency. CTT, colonic transit time.