Efficacy and Safety of Vibrant Capsule vs. Placebo for the Treatment of Chronic Idiopathic Constipation

Study Overview
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Brief Summary
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The study is a prospective, randomized, multicenter, adaptive design, double blinded, placebo-controlled study, to evaluate the efficacy and safety of Vibrant Capsule vs. placebo in relieving constipation in subjects with Chronic Idiopathic Constipation.

Detailed Description
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Subjects came for 4 visits: Screening (visit 1), baseline (visit 2), after 4 treatment weeks from baseline (visit 3) and after 8 treatment weeks from baseline (Final visit , visit 4). A total of 8 treatment weeks Three arms were assessed: Vibrant Capsule mode A administered 5 times per week Vibrant Capsule mode B administered 5 times per week Placebo Capsule administered 5 times per week The difference between the 2 operating modes is in the vibrating sequence during the capsule's operating time. Following Interim Analysis one active arm was dropped and the study continued with 2 arms, placebo and an active arm.

Official Title
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A Prospective, Randomized, Multi-center, Double-Blinded, Placebo-Controlled, 3-Arm Clinical Study to Assess the Efficacy and Safety of Vibrant Capsule, for the Treatment of Chronic Idiopathic Constipation

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Device: Vibrating capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 22 years and older Subjects with Chronic Idiopathic Constipation (CIC) according to Rome III criteria and who have not experienced relief of their symptoms from available therapies (osmotic and stimulant laxatives used for at least one month at recommended dose) Subjects with an average of ≤2.5 Spontaneous Bowel Movements (SBM) per week and ≥1 SBM per week Normal colonoscopy performed within 5 years prior to study participation, unless the subjects are <50 years old and without alarm signs and/or symptoms Subject signed the Informed Consent Form (ICF) Female subjects must have a negative blood pregnancy test during screening, confirmed by a negative urine pregnancy test during baseline and must not be lactating prior to receiving study medication. For females of child-bearing potential, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. All other female subjects must have the reason for their inability to bear children documented in the medical record [i.e., tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)]; in these circumstances, a pregnancy test will not be necessary Exclusion Criteria: History of complicated/obstructive diverticular disease 2. History of intestinal or colonic obstruction, or suspected intestinal obstruction. 3. History of significant gastrointestinal disorder, including any form of inflammatory bowel disease or gastrointestinal malignancy (celiac disease is accepted if the subject has been treated and is in remission) 4. History of gastroparesis 5. Use of any of the following medications: Medications that may affect intestinal motility, prokinetics, anti-Parkinsonian medications, opiates, opioids, calcium-channel blockers, aluminum/magnesium hydroxide With the exception of antidepressants, thyroid or hormonal replacement therapy, when the subject has been on a stable dose for at least 3 months prior to enrollment. 6. Clinical evidence of significant respiratory, cardiovascular, renal, hepatic, biliary, endocrine, psychiatric or neurologic disease 7. Presence of cardiac pacemaker or gastric electrical stimulator. 8. History of, or current eating disorders, such as anorexia, bulimia, or compulsory overeating. 9. Diagnosis of mega-rectum or colon, congenital anorectal malformation, clinically significant rectocele, history of intestinal resection (with an exception for appendectomy, cholecystectomy and inguinal hernia repair), history of bariatric surgery or evidence of any structural abnormality of the gastrointestinal tract that might affect transit 10. History of Zenker's diverticulum, dysphagia, Barrett's esophagus, esophageal stricture or achalasia 11. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs): chronic use is defined as taking full dose NSAIDs more than three times a week for at least six months. Subjects on cardiac doses of aspirin may be enrolled in the study 12. Subjects with pelvic floor dysfunction/defecatory disorder, based on subject history 13. Participation in another clinical study within one month prior to screening. 14. Women who are pregnant or lactating 15. Use of any medication for constipation relief during the study, except as rescue medication, as indicated by study rules 16. Inability to use an electronic daily Diary (on a computer, phone application, tablet or other electronic device) to report bowel movements, symptoms and medication usage 17. Subject participated in a previous Vibrant study 18. Subjects planning to undergo MRI during the study 19. Any known allergy to soybean or beeswax or Calcium Carbonate 20. Any other condition which in the opinion of the investigator may adversely affect the safety of the subject or would limit the subject's ability to complete the study

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Following Interim Analysis one active arm was dropped and the study continued with 2 arms: active arm and Placebo arm
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vibrant Capsule mode A<br>Vibrant Capsule mode A administered 5 times per week | Device: Vibrating capsule<br>* Vibrating Capsule administered 5 times per week<br>|
| Active Comparator: Vibrant Capsule mode B<br>Vibrant Capsule mode B administered 5 times per week | Device: Vibrating capsule<br>* Vibrating Capsule administered 5 times per week<br>|
| Placebo Comparator: Placebo Capsule<br>Placebo Capsule administered 5 times per week | Device: Vibrating capsule<br>* Vibrating Capsule administered 5 times per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSBM1 & CSBM2 Success Rate | defined as number of subjects with an increase from the run-in period of at least one weekly Complete Spontaneous Bowel Movement (CSBM) during at least 6 of the 8 weeks of treatment, and CSBM2 success rate, defined as number of subject with an increase from the run-in period of at least two weekly Complete Spontaneous Bowel Movement (CSBM) during at least 6 of the 8 weeks of treatment. The study will be deemed successful if either the CSBM1 or the CSBM2 success rate is statistically significantly higher in the active arm that was continued after the interim analysis, than in the placebo arm NOTE: A spontaneous bowel movement (SBM) is defined as a bowel movement that occurs at least 48h after laxative/rescue intake and without digital maneuver. A complete spontaneous bowel movement (CSBM) is defined as a spontaneous bowel movement associated with a feeling of complete evacuation by the subject. | 8 weeks of treatment | 
| Adverse event | Safety endpoints include all adverse events related and unrelated to the study treatment in all 3 arms | up to 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| straining using VAS scale (0-10) for straining where 0 is no straining and 10 is unbearable straining | Change from baseline in average straining in all 3 arms | 8 weeks of treatment | 
| consistency using the bristol stool scale (1-7) where 1 = Separate hard lumps, like nuts (hard to pass) and 7 =watery, no solid pieces, entirely liquid | Change from baseline in average stool consistency, using the Bristol Stool Scale in all 3 arms | 8 weeks of treatment | 
| bloating sing VAS scale (0-10) for bloating where 0=No bloating and 10=Unbearable bloating | Change from baseline in average bloating in all 3 arms | 8 weeks of treatment |