Patient Compliance With Vibrating Capsule Predicts Outcome in Chronic Idiopathic Constipation (CIC)

Introduction: Many patients with chronic idiopathic constipation (CIC) are dissatisfied with available medications, suggesting a need for new therapies. A recent phase III trial showed that an orally ingested vibrating capsule (VC) improved stool frequency, bowel and abdominal symptoms and quality of life in patients with CIC. Our aim was to evaluate the impact of compliance/adherence on efficacy of the VC in a post-hoc analysis of a Phase III trial. Methods: Many patients with chronic idiopathic constipation (CIC) are dissatisfied with available medications, suggesting a need for new therapies. A recent phase III trial showed that an orally ingested vibrating capsule (VC) improved stool frequency, bowel and abdominal symptoms and quality of life in patients with CIC. In this 8-week randomized double-blind placebo-controlled Phase III trial, activation of the vibrating capsule (Vibrant®, Yokne'am Illit, Israel) was automatically and remotely recorded, permitting accurate assessment of compliance. Two outcomes were analyzed: CSBM 1, an increase of ≥ 1 CSBM/week and CSBM2, an increase of ≥ 2 CSBMs/week, averaged over the study period and compared to baseline. Results: Patients whose adherence to the recommended number of capsules was >32 capsules ingested over the 8 weeks of treatment (n=117), (out of the recommended 5 capsules per week X 8 weeks = 40 capsules), had higher response rates for both CSBM 1 and CSBM2, compared to either the entire study population or those who ingested < 32 capsules per week (n=42) (Figure and Table). Conclusion: Patients with CIC with >80% adherence to capsule dosing frequency had a superior response, supporting the appropriateness of the proposed dosing schedule. By virtue of its design, this first in class system enables accurate monitoring of compliance when assessing clinical response.Figure 1.: Primary outcome measures showing proportion of complete spontaneous bowel movement 1 and 2 (CSBM1 and CSBM2) responders according to compliance rate and in comparison to the entire study population (intention-to-treat analysis) Table 1. - Impact of compliance on relative efficacy of vibrating capsule (VC) and placebo VC (Vibrant)Mean change from baseline ITT [95% CI] PlaceboMean change from baseline ITT [95% CI] P-value(χ2 test) Entire StudyPopulation(ITT population fromPhase III study) VC n=163Placebo n=149 CSBM1 39.26%[32.10%;46.93%] 22.15%[16.23%;29.47%] 0.0011 CSBM2 22.70%[16.94%;29.72%] 11.41%[7.25%;17.51%] 0.0085 ITT < 80% compliance VC n=117Placebo n=117 CSBM1 26.09%[15.601%;40.26%] 6.25%[1.73%;20.15%] 0.0247 CSBM2 13.40%[6.12%;25.67%] 3.13% [0.55%;15.74%] 0.229) ITT >=80%compliance VC n=46Placebo n=32 CSBM1 44.44%[35.76%;53.48%] 26.50%[19.34%;35.15%] 0.0041 CSBM2 26.50%[19.34%;35.15%] 13.68% [8.60%;21.06%] 0.0144