Constipation Chronic Idiopathic
Conditions
Keywords
Constipation, Vibrating capsule, Chronic Idiopathic Constipation
Brief summary
The objectives are to assess the efficacy and safety of Vibrant capsule administered twice a week
Detailed description
The study is a prospective, randomized, multicenter, adaptive design, double blinded clinical study, to evaluate the efficacy and safety of Vibrant Capsule vs. placebo in relieving constipation in subjects with Chronic Idiopathic Constipation. Two arms will be assessed (at a ratio of 1:1 of Vibrant Treatment vs. placebo): * Vibrant Capsule administered twice a week (Monday and Thursday) * Placebo Capsule administered twice a week (Monday and Thursday) Subjects will come 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. During the entire study period subjects will be asked to refrain from taking any medications or supplements to relieve their constipation. Subjects will be authorized to use rescue medication after 3 consecutive days without a bowel movement
Interventions
DEVICEVibrant capsule
Vibrant capsule - Administered twice a week (Monday and Thursday).
DEVICEPlacebo capsule
Placebo Capsule administered twice a week (Monday and Thursday)
Sponsors
Vibrant Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study. The subjects and the evaluators will be blinded to the treatment allocated to each subject. Each site will assign an unblinded person that will handle all issues related to capsule administration and accountability. The unblinded person will not be involved in any subject's assessments. Rest of the site staff will remain blind throughout the study.
Intervention model description
The objectives are to assess the efficacy and safety of Vibrant capsule administered twice a week
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects aged 22 years and older 2. Subjects with Chronic Idiopathic Constipation (CIC) according to Rome IV criteria 3. Subjects who have not experienced relief of their symptoms from one or more available therapies (for at least one month at recommended dose) or unable to tolerate these therapies 4. Subjects with an average of ≤2.5 Spontaneous Bowel Movements (SBM) per week and ≥1 SBM per week (as a result of at least 1 SBM and not more than 3 SBMs during each of the run-in weeks) 5. Subjects above 50 years old or \<50 years old and with alarm signs should have colonoscopy performed within 10 years prior to study participation. Colonoscopy results should exclude GI obstruction and/or GI malignancy 6. Subject signed the Informed Consent Form (ICF) 7. 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
1. 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. Clinical evidence of current and significant gastroparesis 5. Use of any of the following medications: * Medications that may affect intestinal motility (including but not limited to prokinetics, anti-Parkinsonian medications, opiates, opioids, Verapamil, Nifedipine, iron, magnesium supplements, Tricyclic antidepressants (TCAs), Heparin, Warfarin and Baclofen. * With the exception of antidepressants (other than TCAs), 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, gastric electrical stimulator or any electrical implanted device. 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 capsule's transit 10. History of Zenker's diverticulum, dysphagia, esophageal stricture, eosinophilic esophagitis 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 interventional 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, beeswax, Calcium Carbonate, Gelatin, Glycerin or Titanium dioxide 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CSBM 1 Success Rate | up to 8 weeks of treatment | CSBM1 Success Rate: defined as the number of Participants 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. 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. |
| CSBM2 Success Rate | up to 8 weeks of treatment | CSBM2 Success Rate: defined as the number of Participants 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Straining Based on the Subject's Assessment Recorded in Daily Diaries | up to 10 weeks | Change from baseline in average straining based on the subject's account in daily diary reports. The straining level reported by the patient on a scale ranged from 0 - No straining to 10 Unbearable straining. |
| CSBM1 Expanded Success Rate, | up to 8 weeks of treatment | CSBM1 expanded success rate, defined as the number of Participants with an increase from the run-in period of at least one weekly Complete Spontaneous Bowel Movement (CSBM) during at least 5 of the 8 weeks of treatment. |
| CSBM2 Expanded Success Rate | up to 8 weeks of treatment | defined as the number of Participants with an increase from the run-in period of at least two weekly Complete Spontaneous Bowel Movement (CSBM) during at least 5 of the 8 weeks of treatment. |
| Change From Baseline in Stool Consistency | up to 10 weeks | Change from baseline in average stool 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 |
Countries
United States
Participant flow
Recruitment details
The study recruitment was conducted in 30 clinical sites in the USA from June 2021- September 2022
Pre-assignment details
Following the consent process, subjects who met the study criteria started a run-in period of 2-4 weeks, during which they completed a daily eDiary with questions regrading their bowel movements and constipation symptoms.
Participants by arm
| Arm | Count |
|---|---|
| Active Capsule The Vibrant non-biodegradable capsule administrated twice a week
Vibrant capsule: Vibrant capsule - Administered twice a week (Monday and Thursday). | 44 |
| Placebo The placebo capsule is a softgel biodegradable capsule which is visually similar to the Vibrant active capsule and administrated twice a week
Placebo capsule: Placebo Capsule administered twice a week (Monday and Thursday) | 56 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Change in eligibility criteria | 0 | 1 |
| Overall Study | Run In non compliance | 1 | 2 |
Baseline characteristics
| Characteristic | Active Capsule | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 12.87 | 41.8 years STANDARD_DEVIATION 11.65 | 43.3 years STANDARD_DEVIATION 12.27 |
| Age of constipation onset (years) | 33.1 years STANDARD_DEVIATION 13.8 | 29.6 years STANDARD_DEVIATION 14.77 | 31.2 years STANDARD_DEVIATION 14.39 |
| Race/Ethnicity, Customized Asian/ Pacific Islander | 7 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Caucasian | 8 Participants | 14 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 22 Participants | 27 Participants | 49 Participants |
| Race/Ethnicity, Customized Native American or American Indian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 32 Participants | 13 Participants | 45 Participants |
| Sex: Female, Male Male | 12 Participants | 43 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 56 |
| other Total, other adverse events | 16 / 44 | 11 / 56 |
| serious Total, serious adverse events | 0 / 44 | 1 / 56 |
Outcome results
Primary
CSBM 1 Success Rate
CSBM1 Success Rate: defined as the number of Participants 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. 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.
Time frame: up to 8 weeks of treatment
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Capsule | CSBM 1 Success Rate | 24 Participants |
| Placebo | CSBM 1 Success Rate | 17 Participants |
Primary
CSBM2 Success Rate
CSBM2 Success Rate: defined as the number of Participants 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. 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.
Time frame: up to 8 weeks of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Capsule | CSBM2 Success Rate | 13 Participants |
| Placebo | CSBM2 Success Rate | 12 Participants |
Secondary
Change From Baseline in Stool Consistency
Change from baseline in average stool 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
Time frame: up to 10 weeks
Population: mITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Capsule | Change From Baseline in Stool Consistency | 1.31 units on a scale |
| Placebo | Change From Baseline in Stool Consistency | 0.81 units on a scale |
Secondary
CSBM1 Expanded Success Rate,
CSBM1 expanded success rate, defined as the number of Participants with an increase from the run-in period of at least one weekly Complete Spontaneous Bowel Movement (CSBM) during at least 5 of the 8 weeks of treatment.
Time frame: up to 8 weeks of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Capsule | CSBM1 Expanded Success Rate, | 28 Participants |
| Placebo | CSBM1 Expanded Success Rate, | 23 Participants |
Secondary
CSBM2 Expanded Success Rate
defined as the number of Participants with an increase from the run-in period of at least two weekly Complete Spontaneous Bowel Movement (CSBM) during at least 5 of the 8 weeks of treatment.
Time frame: up to 8 weeks of treatment
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Capsule | CSBM2 Expanded Success Rate | 14 Participants |
| Placebo | CSBM2 Expanded Success Rate | 14 Participants |
Secondary
Straining Based on the Subject's Assessment Recorded in Daily Diaries
Change from baseline in average straining based on the subject's account in daily diary reports. The straining level reported by the patient on a scale ranged from 0 - No straining to 10 Unbearable straining.
Time frame: up to 10 weeks
Population: mITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Capsule | Straining Based on the Subject's Assessment Recorded in Daily Diaries | -2.4 units on a scale |
| Placebo | Straining Based on the Subject's Assessment Recorded in Daily Diaries | -1.70 units on a scale |