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.

The data suggest that chronic airways exposure to IL-25 alone is sufficient to induce allergen- and IgE-independent, asthma-like airways inflammation, remodelling and hyperresponsiveness in mice. Thus, IL-25 is a key molecular target in asthma, irrespective of the coexistence of IgE-dependent mechanisms.

BDNF plays an important regulatory role in gut motility in STC. It was mediated by altering the intestinal innervation structure, as well as smooth muscle secondary degeneration through a mechanism involving TrkB-PLC/IP3 pathway activation.