A Comparison of the Efficacy and Safety of 2 Dosing Regimens, 2 and 5 Times per Week, of an Intraluminal Vibrating Capsule in the Management of Chronic Idiopathic Constipation

Introduction: Chronic constipation is a multifactorial gastrointestinal (GI) disorder. Despite the variety of treatments available, many sufferers remain dissatisfied and close to 90% express an interest in new therapies. The intraluminal vibrating capsule (VC) (Vibrant Ltd., Yokneam, Israel) is the first chemical-free treatment for chronic constipation. Orally administrated, it stimulates bowel movements by mechanically inducing vibrations in the large intestine, which promote mass movements within the colon. We assessed whether VC improves constipation. Methods: Data from 2 studies were aggregated to provide a comparison of two dosing regimens of VC; both enrolled subjects with chronic idiopathic constipation (CIC) who fulfilled Rome III criteria and had comparable inclusion and exclusion criteria. Study 1 was an 8-week double-blind, sham-controlled study (USA & Israel, 2014-2016) that enrolled 163 subjects who ingested 2 capsules per week at the site. The analyses were confined to results of a post-hoc subgroup of 77 subjects who had an average of 1.1 to 2.5 spontaneous bowel movements (SBMs) per week after a 2 week run in period. Bowel function was recorded by daily diary. Study 2 was a 6-week single-arm study (USA, 2016) that enrolled 25 subjects who ingested 5 capsules per week for 6 weeks at home. These subjects had on average at least 1 and less than 3 SBM/week at baseline. The endpoint analyzed was an increase of at least 1 CSBM/week (for at least 6 out of 8 weeks for study 1 and at least 5 out of 6 weeks for study 2). Results: When compared to baseline, the number of complete SBMs (CSBMs) increased in both studies. By week 6, while subjects in study 1 had achieved an average increase of 1.1 CSBM, those in study 2 reported an increase of ˜3.5 CSBMs above baseline. In study 1, the endpoint was met by 35.1% in the active treatment arm and 15% in sham arm (Δ=20.1%, P=0.0307); in study 2, it was met by 66.7%. Using a more conservative endpoint of at least 2 CSBM/week, the responder rate for study 2 was 50%. Significant improvements in various constipation symptoms were also recorded: consistency of stool (study 1: Δ=0.5, P=0.0428; study 2: mean change 2.08), straining (Δ=-1.6, P=0.0072, study 2: mean change -2.69), bloating (Δ=-1.5, P=0.0031, study 2: mean change -0.77). Safety analysis confirmed an excellent safety profile; no serious adverse events (AEs) related to the device were reported in either study. In study 1 (N=163), 13 moderate GI AEs were reported; with the exception of a sensation of vibration, the frequency of all other AEs was similar in active and sham groups. Only one subject in either study discontinued because of an AE Conclusion: In subjects with moderate to severe chronic idiopathic constipation, a vibrating intraluminal capsule provides dose-dependent relief without incurring serious adverse side effects.