Gastroenterology

Gastroenterology

Volume 164, Issue 7, June 2023, Pages 1202-1210.e6
Gastroenterology

Original Research
Full Report: Functional GI Disease
Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation

https://doi.org/10.1053/j.gastro.2023.02.013Get rights and content

Background & Aims

Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation.

Methods

We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed.

Results

Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P = .001 for CSBM1; 22.7% vs 11.4% P = .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial.

Conclusions

In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239)

Section snippets

Trial Design and Oversight

We conducted a multicenter, double-blind, placebo-controlled, 3-arm clinical trial (V270) at 95 centers in the United States between April 2019 and July 2021 to assess the efficacy and safety of the vibrating capsule in the treatment of chronic constipation (Figure 1). All participants signed an informed consent document that was approved by a central or local institutional review board. All patients, study evaluators, treating clinicians, and sponsors were blinded to the treatment allocations.

Characteristics of the Patients

A total of 904 patients with chronic constipation were screened, of whom 312 patients (269 women, 43 men) were randomized to the vibrating capsule activation mode 1 (n = 163) or the placebo (n = 149) arms and were included in the final analysis (Figure 2). An additional 37 patients were randomized to receive the vibrating capsule activation mode 2 arm, but this arm was discontinued after the first phase (Supplementary Table 1, Supplementary Figure 1). Baseline demographic characteristics were

Discussion

In this phase 3 clinical trial, the vibrating capsule significantly increased the percentage of CSBM1 responders as well as CSBM2 responders in patients with chronic constipation when compared with the placebo capsule. Thus, both primary end points were achieved. Furthermore, unlike previous trials of medical therapies for chronic constipation,18, 19, 20 here a CSBM was defined using a 48-hour window for the preceding use of rescue laxative as opposed to the usual 24-hour window to ensure that

Acknowledgments

We thank the following site investigators for their participation in the study: Dinh D., Dunn L., Fogel R., Romero S., Teltser M., Morin P., Torres L., Surowitz R., Reddy V., Wayne J., Beaulieu E., Snook M., Goldstein G., Rubino J., Freeman G., Lumicao B., Greenwald J., Shah S., Zopo A., Wild J., Hellstern P., Murray A., Usdan L., Goldstein G., Whitmer D., Oza A., Friedenberg K.

CRediT Authorship Contributions

Satish S.C. Rao, MD, PhD, FRCP (Corresponding Author: Lead).

Eamonn M.M. Quigley, MD (Co-Investigator: Equal).

William

References (27)

  • G. Basilisco et al.

    Patient dissatisfaction with medical therapy for chronic constipation or irritable bowel syndrome with constipation: analysis of N-of-1 prospective trials in 81 patients

    Aliment Pharmacol Ther

    (2020)
  • M. Camilleri et al.

    Chronic constipation

    Nat Rev Dis Primers

    (2017)
  • J. Tack et al.

    Diagnosis and treatment of chronic constipation—a European perspective

    Neurogastroenterol Motil

    (2011)

    • Cited by (14)

    View all citing articles on Scopus

    Conflicts of interest Satish S.C. Rao serves on the scientific advisory board of Vibrant Ltd and received research grant support for conducting this trial. He also served as a consultant for Sanofi Pharmaceuticals, Salix Pharmaceuticals, Laborie Ltd, Ardelyx pharmaceuticals, Restalsis, and Abbvie pharmaceuticals. Eamonn M.M. Quigley has served on the scientific advisory board of Vibrant Ltd and as an advisor and consultant to 4D Pharma, Axon Pharma, Biocodex, Novozymes, Precisionbiotics, Salix pharmaceuticals, and Vibrant Ltd and has received research support from 4D Pharma, Biomerica, Takeda, and Vibrant Ltd. William Chey has served as a scientific consultant to Vibrant Ltd, Abbvie, Allakos, Alnylam, Ardelyx, Arena, Bayer, Biomerica, Ironwood, Nestle, QOL Medical, Salix/Valeant, Takeda Pharmaceuticals, and Urovant Sciences. Amol Sharma received grant support from Vibrant Ltd, and served on the advisory board for Ironwood Pharmaceuticals, Salix Pharmaceuticals, Takeda Pharmaceuticals, and Phanthom Pharmaceuticals. Anthony J. Lembo has served as scientific consultant for Vibrant Ltd., Allakos, Ardelyx, Arena, Bayer, BioAmerica, Ironwood, QOL Medical, Salix/Valeant, Takeda pharmaceuticals, Mauea Kae Technology, and Gemelli.

    Funding Supported by Vibrant Ltd.

    Data Availability The data will not be available for other researchers.

    View full text
    © 2023 by the AGA Institute.