Chronic Idiopathic Constipation
Conditions
Brief summary
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
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.
Interventions
DEVICEVibrating capsule
Vibrating Capsule administered 5 times per week
Sponsors
Vibrant Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This was a double blind, placebo controlled study and both the participant and the investigator were masked. The study investigators, sponsors and participants were all blinded throughout the study. A research pharmacist/investigator who was not involved with evaluating patients or conducting the study, provided training to the participants and dispensed the correct study arm allocation. This individual had no other role in the study.
Intervention model description
The study design initially comprised 3 arms: 2 active vibrating capsule arms (Modes A and B) and 1 placebo arm. Based on the analysis of the first pre-define phase of the study, active mode B was discontinued and the trial was completed using mode A. Therefore, study results are available only for active A and Placebo arms.
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 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) 3. Subjects with an average of ≤2.5 Spontaneous Bowel Movements (SBM) per week and ≥1 SBM per week 4. Normal colonoscopy performed within 5 years prior to study participation, unless the subjects are \<50 years old and without alarm signs and/or symptoms 5. Subject signed the Informed Consent Form (ICF) 6. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CSBM1 & CSBM2 Success Rate | 8 weeks of treatment | CSBM1Success Rate: defined as the 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. CSBM2 success rate: defined as the 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 (Vibrant Capsule Mode A), 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Straining | 8 weeks of treatment | Change from baseline in average straining using (0-10) scale where 0 is no straining and 10 is unbearable straining |
| Change From Baseline in Average Stool Consistency | 8 weeks of treatment | 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 |
| Change From Baseline in Average Bloating | 8 weeks of treatment | Change from baseline in average bloating using scale (0-10) for bloating where 0=No bloating and 10=Unbearable bloating |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in SBM | 8 weeks of treatment | Change from baseline in weekly number of Spontaneous Bowel Movement (SBM) |
| Change From Baseline in Quality of Life | 8 weeks of treatment | Change from baseline in average PAC-QOL (=Patient Assessment of Constipation Quality of Life) score. The results below present the number of participants who completed PAC-QOL questionnaire and reported an improvement in quality of life from baseline. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 95 centers in the USA. Recruitment began on 8 Apr 2019 and concluded on 16 July 2021.
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 |
|---|---|
| Vibrant Capsule Mode A Vibrant Capsule mode A administered 5 times per week. | 163 |
| Vibrant Capsule Mode B Vibrant Capsule mode B administered 5 times per week. Based on the analysis of the first pre-define phase of the study Arm B was discontinued. | 37 |
| Placebo Capsule Placebo Capsule administered 5 times per week. | 149 |
| Total | 349 |
Baseline characteristics
| Characteristic | Vibrant Capsule Mode A | Vibrant Capsule Mode B | Placebo Capsule | Total |
|---|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.33 | 45 years STANDARD_DEVIATION 12.25 | 45.9 years STANDARD_DEVIATION 13.47 | 46.4 years STANDARD_DEVIATION 13.26 |
| Duration of constipation (years) | 17.90 years STANDARD_DEVIATION 14.15 | 11.20 years STANDARD_DEVIATION 10 | 14.50 years STANDARD_DEVIATION 12.35 | 15.80 years STANDARD_DEVIATION 13.17 |
| Race/Ethnicity, Customized Asian/ Pacific Islander | 10 Participants | 1 Participants | 12 Participants | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 41 Participants | 11 Participants | 39 Participants | 91 Participants |
| Race/Ethnicity, Customized Caucasian | 77 Participants | 22 Participants | 60 Participants | 159 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 31 Participants | 3 Participants | 34 Participants | 68 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 0 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 143 Participants | 28 Participants | 126 Participants | 297 Participants |
| Sex: Female, Male Male | 20 Participants | 9 Participants | 23 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 37 | 0 / 149 |
| other Total, other adverse events | 43 / 163 | 9 / 37 | 26 / 149 |
| serious Total, serious adverse events | 0 / 163 | 0 / 37 | 2 / 149 |
Outcome results
Primary
CSBM1 & CSBM2 Success Rate
CSBM1Success Rate: defined as the 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. CSBM2 success rate: defined as the 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 (Vibrant Capsule Mode A), 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.
Time frame: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vibrant Capsule Mode A | CSBM1 & CSBM2 Success Rate | CSBM1 Success Rate | 64 Participants |
| Vibrant Capsule Mode A | CSBM1 & CSBM2 Success Rate | CSBM2 Success Rate | 37 Participants |
| Placebo Capsule | CSBM1 & CSBM2 Success Rate | CSBM1 Success Rate | 33 Participants |
| Placebo Capsule | CSBM1 & CSBM2 Success Rate | CSBM2 Success Rate | 17 Participants |
p-value: 0.0011Chi-squared
p-value: 0.0085Chi-squared
Secondary
Change From Baseline in Average Bloating
Change from baseline in average bloating using scale (0-10) for bloating where 0=No bloating and 10=Unbearable bloating
Time frame: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vibrant Capsule Mode A | Change From Baseline in Average Bloating | -0.33 units on a scale |
| Placebo Capsule | Change From Baseline in Average Bloating | -0.23 units on a scale |
Secondary
Change From Baseline in Average 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: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vibrant Capsule Mode A | Change From Baseline in Average Stool Consistency | 0.92 units on a scale |
| Placebo Capsule | Change From Baseline in Average Stool Consistency | 0.44 units on a scale |
Secondary
Change From Baseline in Average Straining
Change from baseline in average straining using (0-10) scale where 0 is no straining and 10 is unbearable straining
Time frame: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vibrant Capsule Mode A | Change From Baseline in Average Straining | -1.56 units on a scale |
| Placebo Capsule | Change From Baseline in Average Straining | -1.0 units on a scale |
Other Pre-specified
Change From Baseline in Quality of Life
Change from baseline in average PAC-QOL (=Patient Assessment of Constipation Quality of Life) score. The results below present the number of participants who completed PAC-QOL questionnaire and reported an improvement in quality of life from baseline.
Time frame: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vibrant Capsule Mode A | Change From Baseline in Quality of Life | 113 Participants |
| Placebo Capsule | Change From Baseline in Quality of Life | 90 Participants |
Other Pre-specified
Change in SBM
Change from baseline in weekly number of Spontaneous Bowel Movement (SBM)
Time frame: 8 weeks of treatment
Population: A predefined first-phase analysis was included in the protocol and approved by the FDA. The objective of this first phase analysis was to identify which of the 2 activation modes was superior, and to recommend that mode for the remainder of the study.~Based on the analysis of the study's first phase, mode B was discontinued, and the trial was completed using mode A.~Hence, per the pre-specified outcomes definition, the results are available for mode A \&Placebo arms without the dropped Arm B.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vibrant Capsule Mode A | Change in SBM | 1.4 bowel movements/week |
| Placebo Capsule | Change in SBM | 1.24 bowel movements/week |