A Prospective, Multicenter, Randomized, Double-blind, Sham-controlled Pilot Study to Assess the Efficacy and Safety of Various Vibrating Capsule Modes
Phase: NA
Conditions: Constipation
Sponsor: Vibrant Ltd.

 
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Vibrant Ltd. 
Study Protocol: V-300 
 
 
 
Study number: NCT03329027 
 
Protocol number: 300CLD 
Protocol Date: 10 January 2018, Rev. 02 
 
A prospective, multicenter, 
randomized, double-blind, Sham-
controlled pilot study to assess the 
efficacy and safety of various 
vibrating capsule modes. 
 
 
 
 
 
Confidentiality statement: 
The following confidential information is the property of Vibrant Ltd.  As long as the 
information contained in this protocol has not been published, it may only be used when 
permission has been obtained from Vibrant Ltd. in writing.  It is not permitted to make 
reproductions of all or sections of this protocol.  Commercial use of the information is 
only possible with the permission of the proprietor and is subject to a license fee. 
 
 

 
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1. Sponsor Statement of compliance 
 
The sponsor of this study, Vibrant Ltd., manufacturer of the investigational device, 
legally represented by Lior Ben-Tsur, Chief Executive Officer, states the following: 
 
a. to assume responsibility related to the clinical investigation; 
b. that the treatments used to perform the clinical study are adequate for the device 
under investigation; 
c. that the clinical study, as for the responsibility of the manufacturer, will be 
conducted in conformance with: 
 
The Federal Food, Drug, and Cosmetic Act, as amended, and regulations promulgated 
thereunder (“the Act”) and the United States Food and Drug Administration (“FDA”) 
regulations governing the protection of human subjects and regulations governing clinical 
investigators, The World Medical Association Declaration of Helsinki, titled “Ethical 
Principles for Medical Research Involving Human Subjects”, ICH/GCP guidelines, 
Applicable relevant national legislation, HIPAA as defined in 45. C.F.R. section 164.501 
or relevant national equivalent and following revisions or other analogous internationally 
recognized standards, to be specified, and only after the approval, by the competent 
Ethics Committee, of the investigational protocol, the informed consent and the 
documentation required by the above mentioned standards; 
 
 
 
Print Name: 
 
Signature:  
 
Date: 
 
 
 
Lior Ben-Tsur                         -----------------------------  
         ------------------------ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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2. Investigator Agreement: 
 
 
Prior to participation in this study, a written approval must be obtained from the 
Institutional Review Board, and copy should be provided to the Sponsor, Vibrant Ltd., or 
their authorized representatives, along with the Institutional Review Board approved 
Informed Consent Form.   
 
The Principal Investigator must also: 
• 
Conduct the study in accordance with the study protocol, the Investigator 
Agreement, Declaration of Helsinki, Good Clinical Practices, international 
harmonized standards for clinical investigation of medical devices (Title 21 of the 
Code of Federal Regulations (21 CFR), part 812 (Investigational Device 
Exemptions), the laws and regulations of the countries where the study will take 
place, indemnity/insurance requirements and any other applicable regulations.   
• 
Agree to participate in an appropriate training program as part of the study 
initiation. 
• 
Assure that informed consent is obtained from each subject prior to enrollment, 
using the Institutional Review Board approved form.   
• 
Assure that the study is not commenced until Institutional Review Board approval 
has been obtained. 
• 
Provide all required data and agree to source document verification of study data 
with subject’s medical records.   
• 
Allow staff of the Sponsor and its authorized representatives, as well as 
representatives from regulatory agencies, to review, inspect and copy any 
documents pertaining to this clinical investigation.  
 
The Principal Investigator (PI) may delegate one or more of the above functions to an 
associate or sub-investigator.  However, the PI retains overall responsibility for proper 
conduct of the study, including obtaining and documenting subject informed consent, 
compliance with the study protocol, and the collection of all required data. 
 
 
Principal Investigator Statement: 
I the undersigned, have reviewed this protocol and agree to conduct this study in 
adherence to the study protocol, GCP (Good Clinical Practice) compliance, Ethical 
principles set forth in the declaration of Helsinki and authority regulations for the 
protection of human subjects participating in clinical trials. 
 
 
 
Print Name: 
 
Signature:  
 
Date: 
 
 
----------------- 
 
 ----------------------- 
 
--------------- 

 
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Table of Contents 
 
1. 
Sponsor Statement of compliance ........................................................... 2 
2. 
Investigator Agreement: .......................................................................... 3 
3. 
List of Abbreviations ................................................................................. 7 
4. 
Protocol Synopsis ..................................................................................... 9 
5. 
INTRODUCTION ...................................................................................... 14 
6. 
BACKGROUND ........................................................................................ 14 
7. 
DEVICE NAME AND INTENDED USE........................................................ 16 
7.1 
Device Name ...................................................................................................... 16 
7.2 
Intended Use ...................................................................................................... 16 
8. 
DEVICE DESCRIPTION ............................................................................. 16 
8.1 
Capsule ............................................................................................................... 17 
8.2 
Accessory: activation base unit .......................................................................... 18 
8.3 
Mode of operation ............................................................................................. 19 
9. 
RISKS & BENEFITS ................................................................................... 19 
9.1 
Risks .................................................................................................................... 20 
9.2 
Benefits............................................................................................................... 22 
10. 
ANIMAL INVESTIGATIONS .................................................................. 22 
11. 
HUMAN CLINICAL INVESTIGATIONS ........................................... 23 
12. 
STUDY OBJECTIVE ................................................................................... 38 
13. 
STUDY ENDPOINTS ................................................................................. 38 
13.1 Primary endpoint ............................................................................................... 38 
13.2 Secondary endpoints .......................................................................................... 38 
14. 
STUDY CONDUCT & POPULATION .......................................................... 39 
14.1 Inclusion Criteria ................................................................................................ 39 
14.2 Exclusion Criteria ................................................................................................ 40 
14.3 Duration of Study ............................................................................................... 41 
15. 
STUDY TREATMENT ................................................................................ 41 
15.1 Study Design ....................................................................................................... 41 
15.2 Medical History .................................................................................................. 43 
15.3 Constipation History ........................................................................................... 43 
15.4 Physical Examination .......................................................................................... 43 
15.5 Assessment of pelvic floor dysfunction (defecatory disorder) .......................... 43 
15.6 Blood and urine tests ......................................................................................... 44 

 
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15.7 Screening visit (day -21 to -14) ........................................................................... 44 
15.8 Run-in period (day -21 to -14, to -1) .................................................................. 44 
15.9 Treatment ........................................................................................................... 45 
15.10 Rescue Treatment .............................................................................................. 46 
15.11 Termination visit ................................................................................................ 47 
15.12 Concomitant medication .................................................................................... 47 
15.13 Prohibited medication ........................................................................................ 48 
15.14 Recording ........................................................................................................... 48 
15.15 Study Schedule ................................................................................................... 48 
15.16 Deviations from study protocol ......................................................................... 49 
15.17 Investigative Center Selection Criteria ............................................................... 49 
16. 
ADVERSE EVENTS RECORDING ............................................................... 50 
16.1 Reporting Requirements .................................................................................... 50 
16.2 Definitions .......................................................................................................... 50 
16.3 Anticipated Adverse Events ............................................................................... 52 
16.4 Adverse Event Reporting .................................................................................... 52 
16.4.1 Intensity or Severity ........................................................................................... 53 
16.4.2 Relatedness ........................................................................................................ 53 
16.4.3 Outcome ............................................................................................................. 53 
16.4.4 Treatment or Action taken ................................................................................. 54 
16.5 Expedited Reporting of Serious Adverse Events ................................................ 54 
16.6 Follow- Up of Unresolved Events ....................................................................... 54 
17. 
STATISTICAL CONSIDERATIONS .............................................................. 55 
17.1 Study Design and Objectives .............................................................................. 55 
17.2 Study Endpoints ................................................................................................. 55 
17.2.1 Primary Efficacy Endpoint .................................................................................. 55 
17.2.2 Secondary Efficacy Endpoints ............................................................................ 55 
17.3 Sample size ......................................................................................................... 56 
17.4 Randomization ................................................................................................... 56 
17.5 Blinding ............................................................................................................... 56 
17.6 Data Analysis Sets ............................................................................................... 56 
17.8.1 Intent to Treat (ITT) ............................................................................................ 56 
17.8.2 Modified Intent to Treat (mITT) ......................................................................... 56 
17.8.3 Per-Protocol (PP) ................................................................................................ 57 
17.8.4 Statistical Analysis of Analysis Sets .................................................................... 57 
17.9 Statistical Analysis .............................................................................................. 57 
17.9.1 General Considerations ...................................................................................... 57 
17.9.2 Significance levels and handling of type I error ................................................. 57 
17.9.2.1 
Type I Error .................................................................................................. 57 
17.9.3 Demographic and Other Baseline Variables ...................................................... 57 
17.9.4 Disposition of Subjects ....................................................................................... 58 
17.9.5 Efficacy Analysis ................................................................................................. 58 

 
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17.9.6 Treatment by Center Interaction ....................................................................... 58 
17.9.7 Safety Analysis .................................................................................................... 59 
17.9.8 Handling of Missing Data ................................................................................... 59 
17.9.9 Interim Analysis. ................................................................................................. 59 
18. 
DATA MONITORING PLAN ...................................................................... 59 
19. 
DATA CONFIDENTIALITY ......................................................................... 61 
20. 
FUNDING ................................................................................................ 61 
21. 
ETHICS .................................................................................................... 61 
22. 
INFORMED CONSENT ............................................................................. 62 
23. 
REGULATORY AND HEALTH AUTHORITY AUDITS ................................... 63 
24. 
ELECTRONIC REPORTING OF DATA ........................................................ 63 
25. 
RECORD RETENTION ............................................................................... 64 
26. 
PROTOCOL MODIFICATIONS .................................................................. 64 
27. 
PUBLICATION POLICY ............................................................................. 64 
28. 
SUBJECT / STUDY DISCONTINUATION .................................................... 64 
29. 
DEVICE ACCOUNTABILITY ....................................................................... 65 
30. 
APPENDICES ........................................................................................... 66 
31. 
REFERENCES ........................................................................................... 66 
 
 

 
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3. List of Abbreviations 
 
% 
Percent 
AE 
ADE 
AGA 
AR 
Adverse Event 
Adverse Device Effect 
American Gastroenterological Association 
Authorized Representative 
BMI 
BUN 
CSBM 
Body Mass Index 
Blood Urea Nitrogen 
Complete Spontaneous Bowel Movement 
eCRF 
CI 
Electronic Case Report Form 
Confidence Interval 
CIC 
Chronic Idiopathic Constipation 
DSMB 
Data and Safety Monitoring Committee 
EC 
Ethics Committee 
ECG 
EDC 
FA 
FC 
Electrocardiogram 
Electronic Data Capture 
Full Analysis Set 
Functional Constipation 
GCP 
Good Clinical Practice 
FDA 
Food and Drug Administration 
IBS-C 
ICF 
Irritable Bowel Syndrome with Constipation 
Informed Consent Form  
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IFU 
Instruction for Use 
IRB 
ISF 
Institutional Review Board 
Investigator Site Files 
ITT 
Intent To Treat 
Mg 
Milligram 
µg 
Microgram 
Min 
MFR 
NCAs 
NSAIDs 
minute(s) 
Manufacturer 
National Competent Authorities 
Non-Steroidal Anti-Inflammatory Drugs 
mITT 
Modified Intent to Treat 
OTC 
PAC-QOL 
PEG 
PI 
PP 
QOL 
Over The Counter 
Patient Assessment of Constipation Quality of Life questionnaire 
Polyethylene glycol 
Principal Investigator 
Per Protocol 
Quality of life 
SAE 
SADE 
SBM 
Serious Adverse Event 
Serious Adverse Device Effect 
Spontaneous Bowel Movement 

 
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TSQM 
US 
USADE 
Treatment Satisfaction Questionnaire for Medication 
United States 
Unanticipated Serious Adverse Device Effect 

 
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4. Protocol Synopsis 
 
Name 
A prospective, multicenter, randomized, double-blind, Sham-controlled 
pilot study to assess the efficacy and safety of various vibrating capsule 
modes. 
Indication 
The Vibrant Capsule is intended for the treatment of subjects with 
Functional Constipation. 
Objectives 
The objectives are to assess the efficacy and safety of the Vibrant capsule 
administered 2 times per week  
Design 
The study is a prospective, adaptive, multicenter, randomized, double-
blind, Sham-controlled pilot study, to evaluate the efficacy and safety of 
the Vibrant Capsule in relieving constipation in subjects with functional 
constipation. 
 
Three arms will be assessed:  
- 
Vibrant Capsule with vibrating mode 1 administered 2 times per 
week 
- 
Vibrant Capsule with vibrating mode 2 administered 2 times per 
week 
- 
Sham Capsule administered 2 times per week 
 
The study will be performed in up to 15 centers in the USA. 
 
Subjects will be followed continuously for at least a 2 weeks run-in  period 
and then be randomized to either Vibrant or Sham capsules for a treatment 
period of 8 weeks. The first 2 weeks of treatment will be considered as a 
subjects’ training period.  
Data reporting will be done on an electronic Case Report Form (eCRF) and 
an eDiary. 
Subjects will be asked to refrain from taking any medication or supplement 
to relieve their constipation, during the entire study period.  
After the run-in period, the subjects will return and eligibility will be re-
assessed. Subjects will be trained on how to use the base unit and will 
swallow the first capsule on site the day of baseline visit. They will activate 
and ingest the rest of the capsules at home by themselves, using the base 
unit.  
Subjects will be instructed to complete a simple subject eDiary each day 
throughout the duration of the study. A final visit will take place at the end 
of the 8 week treatment period.  
Subjects will receive phone calls at least once a week and subject 
compliance will be monitored during the 8 weeks of the study. 
 

 
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Subjects will be authorized to use rescue medication after 3 consecutive 
days without a bowel movement. Subjects will report their daily bowel 
movements and use of medication using the eDiary.  
Data about time of activation of the capsules will be automatically 
registered and transmitted by the base unit. 
Subjects will be requested to ingest the capsules at a specific time of the 
day. 
  
Study duration 
Study duration is 10 to 11 weeks 
- 
2 to 3 weeks of run-in 
- 
8 weeks of treatment 
Endpoints 
The two primary efficacy endpoints are the CSBM1 success rate, defined 
as 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 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. 
 
Secondary efficacy endpoints include:  
- 
Change from baseline in average straining. 
- 
Change from baseline in average stool consistency, using the 
Bristol Stool Scale 
- 
Change from baseline in average bloating. 
- 
SBM success rate, defined as as an increase from the run-in period 
of at least one weekly Spontaneous Bowel Movement (SBM) 
during at least 6 of the 8 weeks of treatment. Subjects with less than 
2 weeks (with at least 5 days per week) of valid diary during the 
treatment period will be considered as non-evaluable. 
 
Additional efficacy endpoints  
- 
Change from baseline in weekly number of Spontaneous Bowel 
Movement (SBM). 
- 
Change from baseline in weekly number of Complete Spontaneous 
Bowel Movement (CSBM). 
- 
Change from baseline in average abdominal gas. 
- 
Change from baseline in average abdominal pain. 
- 
Change from baseline in abdominal discomfort. 
- 
Time to occurrence of spontaneous bowel movement after first 
capsule activation. 
- 
Treatment satisfaction score using the TSQM (Treatment 
Satisfaction Questionnaire for Medication) 
Ease of use of the device.  
- 
Safety endpoints include all adverse events related and unrelated to 
the study treatment. 

 
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Subject 
Population 
Subjects with Functional Constipation refractory to existing treatments.  
No. of Subjects The study is planned to enroll approximately 66 subjects (20 subject per 
arm and an expected 10% drop out rate). 
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 <3 Spontaneous Bowel Movements 
(SBM) per week and ≥1 SBM per week 
4. Normal colonoscopy performed within 10 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 
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. History of gastroparesis 
5. Use of any of the following medications:  
o Medications that may affect intestinal motility, prokinetics, 
anti-Parkinsonian medications, opiates, opioids, calcium-
channel blockers, aluminum/magnesium hydroxide 
o 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. 

 
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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. 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 
Statistical 
analysis 
No sample size assessment was performed.  
A sample size of 15 subjects in each study arm is deemed sufficient to 
achieve the trial goals.  
The sample size will be increased to at least 66 subjects (22 in each arm) 
to account for a potential 10% of drop-outs. 
 
Statistical analyses will be performed using SAS® v9.4 or higher (SAS 
Institute, Cary NC, USA). 
Baseline demographic and other baseline characteristics, together with 
safety analyses will be performed on all enrolled subjects. Baseline 
values are defined as the last valid value prior to treatment. 
The efficacy endpoints are mainly descriptive in nature. 
Nevertheless, if statistical tests will be performed, they will be two-sided 
and nominal p-values will be presented. Where confidence limits are 
appropriate, non-adjusted two-sided 95% confidence interval will be 
constructed. 
 

 
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The subject’s CSBM1 success status (i.e. if the subjects achieve an 
increase from baseline of at least 1 weekly CSBM during at least 6 out of 
the 8 treatment weeks) will be modeled by study arm with a logistic 
regression model, with the baseline weekly number of CSBM and site as 
covariates. The adjusted success rate per study arm, and their difference 
between the groups will be presented along with their respective 95% 
Confidence Intervals (CI).  
 
The CSBM2 success rate will be analyzed in the same manner 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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5. 
INTRODUCTION 
 
This document is a clinical research protocol and the described study will be conducted in 
compliance with the protocol, standards of Good Clinical Practices and associated 
regulations, and all applicable research requirements. 
6. 
BACKGROUND 
 
Chronic constipation is a common gastrointestinal disorder in the general population. It is 
estimated that chronic constipation affects between 2 and 27% of the population. A 
majority of chronic constipation sufferers are women, who represent three-fourths of 
those affected1. 
Constipation may be primary (Chronic Idiopathic Constipation (CIC), Irritable Bowel 
Syndrome with Constipation (IBS-C)) or secondary to other factors (such as drugs like 
opioids, colorectal cancer, diabetes, Parkinson’s disease or spinal cord injury). It is 
estimated that 100 million adults in the United States (US) have chronic pain2.  
There is no widely accepted definition of chronic constipation. Although physicians often 
define constipation based on stool frequency, subjects experience constipation as a multi-
symptom disorder that includes infrequent bowel movements, hard or lumpy stools, 
straining, bloating, a feeling of incomplete evacuation after a bowel movement and 
abdominal discomfort3. The Rome Foundation has created symptom-based diagnostic 
criteria for chronic constipation. To meet the definition of chronic constipation, the 
criteria must be fulfilled for the prior 3 months with symptom onset at least 6 months 
prior to diagnosis4.  
Chronic constipation impacts quality of life and is perceived by subjects as a severe 
disease3.  Adding to the burden of disease, constipation is among the ten most expensive 
gastrointestinal diseases in terms of direct and indirect healthcare costs5. A recent 
systematic review of the disease burden of IBS and CIC found the attributable direct 
costs of IBS to range from approximately $1,600 to $7,500 per subject-year, whereas the 
attributable direct costs of CIC range from approximately $1,900 to $7,500 per subject-
year6. 
Although a variety of treatment options are available for chronic constipation, subjects 
have reported low satisfaction with current treatment alternatives in multiple published 
studies.  Thus, there is a need for additional therapeutic options that address subject 
symptoms and preferences. 
Constipation Management  
The American Gastroenterological Association (AGA) has established a treatment 
algorithm for constipation that provides multiple therapeutic steps depending on severity 
of symptoms.  See http://www.gastrojournal.org/article/S0016-5085(12)01545-4/pdf. The 

 
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first step in the treatment of constipation focuses on lifestyle modification with three 
main parameters: adequate fluid intake, a high fiber diet and regular physical activity. 
Fiber absorbs water, increases stool bulk, and in doing so stimulates the bowel to 
decrease stool transit time and ease evacuation.  Medicinal and dietary fiber supplements, 
such as psyllium, can be added to the high fiber diet or used as primary therapy. 
If lifestyle modification does not produce satisfactory results, subjects have access to a 
number of FDA-approved products (Food and Drug Administration), available both over 
the counter (OTC) and by prescription. Stool softeners (docusate sodium, docusate 
calcium) act by decreasing surface tension to allow water to enter the bowel more readily, 
making the stool softer, which makes it easier and less painful to pass. However, there is 
currently limited data on the efficacy of stool softeners in subjects with constipation1.  
Osmotic laxatives are also available, including polyethylene glycol (PEG), lactulose, 
magnesium hydroxide, magnesium citrate, magnesium sulfate, and sodium phosphate. 
PEG and lactulose have been shown to improve stool frequency and stool consistency1,6,7.   
Osmotic laxatives contain poorly absorbed ions or molecules that retain water in the 
intestinal lumen. Although effective, they can cause bloating and cramping.  In addition, 
due to their mechanism of action, they should be used with caution in older adults and in 
subjects with renal impairment because of the risk of dehydration and electrolyte 
disturbances. 
Stimulant laxatives include senna, bisacodyl or sodium picosulphate. They induce fluid 
and electrolyte secretion by the colon or induce peristalsis in the colon, thereby producing 
a bowel movement.  
Recent advances in research have resulted in new classes of medication for the treatment 
of constipation, available on prescription. For example, linaclotide is an agonist of 
guanylate cyclase-C receptors, and increases chloride, bicarbonate and fluid secretion 
into the intestinal lumen, lubricating the stool and accelerating gastrointestinal transit. 
Linaclotide was FDA-approved in 2012 for CIC and IBS-C. Adverse events include 
diarrhea, which leads to discontinuation of the medication in approximately 5% of 
subjects8.  In total, 8% of subjects in linaclotide clinical trials discontinued due to adverse 
events, and 27% had their dose reduced or suspended secondary to adverse reactions, the 
majority of which were diarrhea or other gastrointestinal adverse reactions.  See 
http://www.accessdata.fda.gov/drugsatfda_docs/label/ 2014/202811s004lbl.pdf 
 
Lubiprostone is approved for use in women with IBS-C and in men and women with 
CIC, as well as opioid-induced constipation in subjects with non-cancer pain. It is a 
selective chloride channel activator, increasing ion and fluid secretion. The main adverse 
events associated with lubiprostone are mild to moderate nausea and diarrhea2,9.  
Approximately 29% of subjects who received lubiprostone 24 mcg twice daily in clinical 
trials experienced nausea; 4% of subjects had severe nausea while 9% of subjects 
discontinued treatment due to nausea. Approximately 12% of subjects who received 

 
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lubiprostone 24 mcg twice daily experienced diarrhea; 2% had severe diarrhea while 2% 
discontinued treatment due to diarrhea.  In addition, it has been reported to cause 
dyspnea, which was reported in 2.5% of the treated chronic idiopathic constipation 
population and 0.4% in the treated IBS-C population. Although not classified as serious 
adverse events, some subjects discontinued treatment because of this event. These events 
have usually been described as a sensation of chest tightness and difficulty taking in a 
breath, and generally have an acute onset within 30-60 minutes after taking the first dose. 
They generally resolve within a few hours after taking the dose, but recurrence has been 
frequently reported with subsequent doses.  See 
http://www.accessdata.fda.gov/drugsatfda_docs/label/ 2008/021908s005lbl.pdf.   
In subjects with severe chronic constipation, surgery may be considered; however, it is 
generally limited to use in the most severe cases after medical management has failed to 
provide adequate relief.  In subjects with severe incapacitating slow transit constipation, 
colectomy with ileorectal anastomosis can improve constipation and related 
symptoms10,11. 
In summary, while there are a variety of treatments available for constipation, there is 
currently no satisfactory treatment for many constipated subjects:  a US study showed 
that 47% of constipated subjects are not completely satisfied with their current 
constipation treatment3, while a European study showed that only 27% of European 
subjects are satisfied with current treatment options5. Furthermore, many subjects become 
refractory to one or more OTC laxatives with chronic use, which may cause frustration 
for both the clinician and the subject, and ultimately leads many subjects to abandon 
therapy and remain dissatisfied with their condition2. Nearly 90% of subjects express 
interest in new therapies12.  
 
7. 
DEVICE NAME AND INTENDED USE 
7.1 
Device Name 
 
 
Vibrant Capsule 
 
7.2 
Intended Use 
 
 
The Vibrant Capsule is an orally administrated capsule intended for the treatment of 
Functional Constipation (FC) in subjects aged 22 years or older. 
 
8. 
DEVICE DESCRIPTION 
 

 
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The Vibrant Capsule is designed to mechanically induce a peristaltic wave in the large 
intestine, thus aiding in relieving constipated subjects. Constipation relief is achieved by 
the capsule’s vibrations impinging on the gastrointestinal wall, consequently inducing 
peristaltic activity which promotes transit and facilitates defecation. 
 
The Vibrant Capsule has several important features: 
• Small Dimensions. 
• Easy to swallow (smooth shell). 
• Delay Mechanism - A delay mechanism was incorporated in this device to allow 
sufficient time for the capsule to arrive at the large intestine before it starts 
vibrating. The delay mechanism is the time between swallowing the capsule and 
activation and inducing vibrations within the large intestine. This is obtained by a 
simple software programing mechanism. 
• Sequence Mechanism – sequence of vibration, specifically adapted for subjects 
with constipation. 
The capsule is activated by an electromagnetic signal which carries an Activation Code 
using the activation base unit prior to swallowing the capsule. 
 
8.1 
Capsule 
 
The Vibrant Capsule is comprised of a flat motor, electronic card and batteries, all 
encapsulated in a 2-piece shell (please refer to Figure 1 below). The capsule is activated 
by an electromagnetic signal which carries the Activation Code using the activation base 
unit, prior to swallowing the capsule. 
 
 
 
 
 
 
The capsule dimensions are: 
 
Length: 24.2 ± 0.1 mm 
 
Diameter: 11.3± 0.1 mm 
 
The capsule shell is made of a well-known biocompatible material: PC MAKROLON 
2458. 
Before starting the vibrating action and to ensure the capsule has arrived at the large 
intestine, the company has integrated a tightly controlled vibrating algorithm that will 
define number of hours from the activation to the vibrating phase (delay time). 
This delay will allow the capsule to reach the large intestine before starting the 
vibrations. 
  
The difference between the 3 active operating modes is in the vibrating sequence during 
the capsule's operating time. 
 
The vibration rate is the following: 

 
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Activation Delay is set to 8 ± 1 hours while the vibration rate is 190 vibration cycles in an 
hour; each cycle consists of 3 seconds of vibration and 16 seconds of repose (rest). Total 
vibrating time per 1 operating hour is 9.5 min. 
 
The capsules are packaged in a blister of 5 or 10 units (cf. Fig. 2 below).  
 
 
 
Figure 1.  The blister of 5 or 10 capsules 
 
 
 
8.2 
Accessory: activation base unit 
 
A user friendly activation base was developed by the company for subject use 
(please refer to Fig 3 below). The activation base (or base unit) is meant to be used at 
home by subjects. The base unit is easy to use and requires a simple training before 
taking it home. Subjects will activate the capsule themselves at home.  
 
 
 
 
The activation base is composed of: 
 
• An electronic circuit board  
 
• Electromagnetic antenna bedding the capsule.  
 
 
1. Base Unit 
2. USB cable  
3. AC/DC USB adapter  
 
 
 
1. Base Unit Cover 
2. The "Ready" Green Light Indicator 
3. The Designated Groove for Capsule 
4. The "X" Red Light Indicator 
5. The "ON" Green Light Indicator 
 
 
 
 
 
Figure 2. Activation base: description of components and image 

 
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Setting up the base unit 
First, the user connects the base unit to an electricity outlet, with the USB cable and 
AC/DC adapter. The green “ON” light on the base unit turns on and a short “buzz” is 
heard, indicating that the base unit is ready for use.  
 
Activation of the Vibrant Capsule using the base unit 
 
8.3 
Mode of operation 
The Activation base is shipped in a protective package containing the following: 
- 
Base Unit 
- 
USB cable  
- 
AC/DC USB adapter  
- 
Instructions for use 
The Vibrant Capsules are shipped in a blister containing 5 or 10 capsules. 
 
Capsule activation: 
1. The capsule will be placed in the designated groove in the center 
2. The green "Ready" indicator light turns on and a short "buzz" is heard 
3. The capsule is ready to be administered by the subject. 
4. Capsule will reach the large intestine (within approximately 6-8 hours) and start 
vibrating, consequently inducing peristaltic activity.  
5. Capsule will be extracted from the body during normal bowel movement. 
 
Additional details can be found within the Investigator's Brochure (Document # 
114CLD,) and the Instruction For Use (IFU) for the vibrating capsule (Document # 
117LAB). 
 
9. 
RISKS & BENEFITS 
 
The Vibrant Capsule is designed according to international standards for medical devices. 
Compliance with these standards ensures that the device can be used safely in human 
beings.  
Biocompatible materials are used for the vibrating capsule components. The use of 
biocompatible materials should protect the subject of any hazardous from possible 
adverse events.  
 
The device classification according to ISO10993-1 and FDA’s guidance Use of 
International Standard ISO-10993-1:2009, "Biological Evaluation of Medical Devices 
Part 1: Evaluation and Testing" :  Draft Guidance for Industry and Food and Drug 
Administration Staff (“FDA Biocompatibility Guidance”) is as follows: 
Category:  Surface device. 

 
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Contact duration: permanent contact (>30 days) 
Contact:  breached or compromised surfaces. 
 
According to this classification, the following tests were performed, all of which had 
passing results: Cytotoxicity Study Using the ISO Elution Method, Bacterial Reverse 
Mutation Study, ISO Intracutaneous Study in Rabbits, ISO Systemic Toxicity Study in 
Mice, ISO Guinea Pig Maximization Sensitization Test, Mouse Peripheral Blood 
Micronucleus Study, Genotoxicity: Mouse Lymphoma Assay, ISO 10993-18 - Chemical 
Characterization 
 
A biological risk assessment of the Vibrant Capsule has also been performed by 
NAMSA in accordance with ISO 10993-1:2009 requirements. The purpose of this study 
is to use information from biological safety studies of the materials used to manufacture 
the Vibrant Capsule, chemical characterization data, and biological safety test results on 
the device to support and demonstrate the overall biological safety of the Vibrant 
Capsule. This assessment focuses on the requirements of ISO 10993-1:2009, EN ISO 
14971:2012, FDA General Program Memorandum #G95-1 and the 2013 Draft 
Biocompatibility Guidance, and the European Union Medical Device Directive 
93/42/EEC. 
 
The company also evaluated the mechanical, structural integrity, electrical safety, shelf 
life and other characteristics of the Vibrant Capsule when subjected to clinical use 
conditions.  
 
Testing performed included the following:  
a. Visual inspection 
b. Dimensional verification of the capsule 
c. System delay mechanism verification test 
d. pH Resistance test 
e. Mechanical integrity test  
f. Evaluation of capsules Vibrations sequence 
g. Electrical safety and EMC  
h. Environmental and transportation test. 
 
Vibrant has completed two animal studies and three human clinical investigations with 
the Vibrant Capsule: an initial phase 1 study in healthy volunteers, a phase 2a, single-arm 
study with both chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS-
C) subjects, and a phase 3, double-blind sham-controlled study with CIC subjects.   
 
9.1 
Risks 
 
The Vibrant capsule has been designed to mechanically induce a normal peristaltic wave 
in the large intestine, thus aiding in relieving constipated subjects.  
 

 
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The capsule moves through the gastrointestinal system, without interacting with any other 
body system and does not deliver medication of any kind. The Vibrant capsule targets 
basic pathophysiological factors contributing to chronic constipation by inducing intrinsic 
contractile activity without using chemical supplements. The capsule operates without 
any biological interference. 
 
The capsule has been sealed up by using a biocompatible shell and will remain sealed up 
until it has been excreted out of the human body, thus ensuring that, as it transits the 
gastrointestinal tract, there will be no unwanted outputs of energy or substance. This has 
been evaluated and confirmed in preclinical testing (please refer to the study 
investigational brochure). 
 
The capsule coating (a biocompatible and widely used shell) protects the subject from 
any potential hazards that might be associated with its contents. The energy of the 
batteries is harmless and cannot leak while the capsule remains intact (break force was 
tested up to 60 Kgf/cm²). The capsule was tested for Safety and EMC 60601 trials. No 
ionizing radiation is emitted and no thermal energy generated. 
 
Device manufacturing and assembly is done in an ISO 13485:2003 facility. 
 
Safety in Animal and Human Clinical Investigations 
 
No safety concern was raised during animal and human clinical investigations. 
 
The animal studies and phase 1 human investigation demonstrated safety of the capsule 
to support subsequent studies in the target population. All capsules were extracted safely 
with no adverse events and all clinical and laboratory results were within normal values. 
 
During the phase 2a clinical investigation, there were no problems with the evacuation of 
the capsule in any subject. Of the 26 subjects who completed the study, 12 reported 
Adverse Events (AEs). In all, 27 AEs were observed in these 12 subjects, none serious. 
Nine of the 27 AEs may potentially have been related to the study. They were: 
- 
Abdominal pain: 3 subjects (11.1%), 5 events 
- 
Diarrhea: 2 subjects (7.7%), 2 events 
- 
Flatulence: 2 subjects (7.7%), 2 events. 
 
All adverse events were mild, and all resolved without any action taken. Flatulence lasted 
for 7 and 15 days.  One event of abdominal pain (stomach ache) lasted one day. All other 
events were resolved within one day. 
 
Vital Signs and ECG results did not demonstrate any safety concerns.  
 
During the double-blind, sham-controlled, phase 3 clinical investigation involving 154 
subjects the overall rates of adverse events was not statistically different between sham 
and active groups with the exception of a sensation of vibration (not resulting in  

 
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discomfort or pain) which was more common in the active group. The rate of occurrence 
of bloating/flatulence was numerically but not statistically significantly higher in the 
sham group, and the rate of diarrhea was numerically but not statistically significantly 
higher in the active group.  
No subject discontinued treatment because of an adverse event and no serious adverse 
events related to the device were reported. There was no problem with evacuation of the 
capsule in any subject. 
 
9.2 
Benefits 
 
 
Human Clinical Investigations 
 
Phase 1, 2a and 3 studies showed clinical benefits with the Vibrant Capsule: the capsule 
increased the number of weekly SBM among subjects with constipation and improved 
constipation symptoms, such as straining, bloating and stool consistency. 
 
During the phase 2a, single-arm, investigation, there was a significant increase in the 
mean number of SBMs/week for the entire study population. The increase in the mean 
number of SBMs/week for the entire study population was 1.60 ± 1.09; from 2.19 ±0.67 
to 3.79 ± 1.31 (p < 0.001). The mean number of weekly SBMs increased from baseline in 
23 of the 26 subjects (88.5%).   
In sub-group analyses by etiology of constipation, the mean increase in SBM was 1.46 ± 
1.08 (p = 0.001) for subjects having IBS-C and 1.75 ± 1.14 (p = 0.001) for subjects with 
functional constipation. For the entire study population and for the two sub-groups, each 
weekly mean SBM was higher than the mean at baseline. 
 
In the phase 3 investigation, a post hoc subgroup analysis was performed based on 
subject severity of constipation during the baseline period (average weekly number of 
SBM).   
Subjects with ≥1.1 and <2.5 SBMs at baseline were selected. They represented half of the 
population (N=77).  This subgroup demonstrated a 12% increase in the responder rate 
(increase of at least 1 SBM/week) for the Vibrant Capsule (59.5%) compared to the 
control (47.5%).   
In addition, clinical benefit was observed in the Bristol Stool Score, straining and 
bloating: they were significantly improved in the Vibrant arm, compared to sham 
(respectively p=0.0237, p=0.0072 and p=0.0031).  
 
 
10. 
ANIMAL INVESTIGATIONS 
 
Two animal studies were conducted using the Vibrant Capsule: 

 
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The initial study was approved by Helsinki committee for animal studies (approval no. 
IL-089-09-2008), and performed at the Technion – Israel Institute of Technology. The 
study was overseen by the committee for the supervision of animal experiments. Study 
objectives were to evaluate the safety and physiological effect of the vibrating capsule in 
3 dogs. On study initiation the dogs were given sham capsules to evaluate defecation 
time, clear passage of the capsule and safety. After approximately 1 week each animal 
swallowed a vibrating capsule in different intervals starting from 3 days to two week 
intervals during a 6-month period. 
 
Final analysis showed that the capsules were safe for use – they were not damaged even 
when bitten by the dogs. There was no evidence of any discomfort or adverse effects on 
the dog’s health. Evidence of effectiveness of the capsule was indicated by reduced 
defecation time with the vibrating capsule compared to the Sham, without creating 
artificial constipation conditions in the dog's gastrointestinal tract.  
 
The second study was conducted at the Rambam Hospital in Haifa, Israel.  The study was 
approved by the Helsinki committee for animal trials (approval no. IL-130-11-2009).  
Study objectives were to evaluate the safety and physiological effect of vibrating capsule 
in 2 dogs. On study initiation the dogs were given sham capsules to evaluate defection 
time, clear passage of the capsule and safety. After approximately 2 days each animal 
ingested a vibrating capsule every second day for two weeks' time and was followed for 
an additional month. Capsule delay time was adjusted for the animal model (8 hours for a 
smaller dog and 16 hours for a bigger dog). Clinical observations were recorded by lab 
personnel to ensure no signs of distress, pain, vomiting or irregular behavior. In addition 
X-ray was used to verify capsule location and vibrating movement. The time of 
defecation and stool consistency were recorded. The capsules were retrieved from the 
dog stools. Capsule integrity was confirmed; capsules were whole with no defects in seal, 
no ruptures, no shell cracks or any other damage.   
 
In all the animals the capsule were passed by the dogs without any adverse effects to the 
dog and/or any damage to the capsules. There was no evidence that the capsule's colon 
transit or its vibration caused any adverse effect to the dog's physical health and behavior.  
Evidence of effectiveness of the capsule was indicated by reduced defecation time with 
the vibrating capsule compared to the Sham. Moreover, one dog suffered from 
constipation for 4 days (not induced by the study), which was relieved by the vibrating 
capsule.  
 
11. 
HUMAN CLINICAL INVESTIGATIONS 
 
Vibrant Ltd. has completed three human clinical investigations. 
 
Total Exposure – Human Clinical Investigations 
The human clinical investigations performed by Vibrant exposed a total of 186 
participants, healthy or constipated, to either the Vibrant Capsule or the Sham Capsule. 

 
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In total, 109 subjects received the Vibrant Capsule.  The number of subjects who received 
the Vibrant Capsule were as follows:  
- 
6 healthy volunteers 
- 
89 subjects with CIC 
- 
14 subjects with IBS-C. 
 
The remaining 77 subjects who participated in clinical investigations received the Sham 
Capsule. 
 
Phase 1 clinical investigation – healthy volunteers 
 
An initial clinical study was approved and initiated in 2 sites in Israel (Tel-Aviv Sourasky 
Medical Center and The Holy Family Hospital, Nazareth), from March 8 to 24th, 2011. 
The study was initially approved for use in 6 healthy volunteers in order to evaluate the 
safety of the Vibrant Capsule in a prospective, open-label, single group study. 
Six consecutive healthy volunteers (3 men and 3 women) ages 21 to 41 years, all 
fulfilling the exclusion/exclusion criteria, were enrolled in the study. During the Baseline 
study visit, subjects were evaluated for eligibility and went through physical examination, 
vital sign measurements, ECG measurements and blood tests, which were all within the 
normal values. Eligible subjects were asked to take 1 vibrating capsule by the study 
personnel.  Subjects were followed for 7 days on their normal bowel movements and 
excretion of the capsule.  One week following the baseline visit, subjects returned for a 
visit and repeated the physical examination, vital sign measurements, ECG measurements 
and blood tests.  
All capsules were evacuated from the body, along with stool, safely with no adverse 
events. Average time for capsule excretion was 2.2 days (2 days for 4 subjects, 1 day for 
1 subject, and 6 days for 1 subject). All clinical and laboratory results were within normal 
values.  Thus, this preliminary study demonstrated safety of the capsule to support 
subsequent studies in the target population. 
 
Phase 2a clinical investigation 
 
The Phase 2a clinical trial was conducted in the Departments of Gastroenterology and 
Hepatology at the Tel-Aviv Sourasky Medical Center and at The Nazareth Holy Family 
Hospital, beginning in July 2011. The study was an open-label, pilot trial.  
The primary endpoint was safety, assessed descriptively by summarizing adverse events 
(AEs), clinical laboratory test results, vital sign measurements, and ECG measurements.  
The secondary endpoint was efficacy, determined as an increase of more than one 
spontaneous bowel movement (SBM)/week during the 7.5 weeks of treatment compared 
to the 2-week run-in period.  The number of spontaneous bowel movements was 
calculated as a weekly average. 
 
Inclusion and exclusion criteria 
Inclusion criteria were: 
1. Subjects age 18-70 years 

 
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2. Subjects with IBS-C according to the Rome III criteria, OR Subjects with Chronic 
Idiopathic Constipation according to the Rome III criteria. 
3. Subjects with 1-3 bowel movements per week. 
4. Subjects who did not have satisfactory symptom improvement of their symptoms 
with other available treatment(s). 
5. Colonoscopy performed in the past 5 years prior to study participation, unless the 
subjects are <50 years old and without alarming signs 
6. Ability of subject to understand character and individual consequences of clinical 
trial 
7. Written informed consent must be available before enrollment in the trial 
8. For women with childbearing potential, adequate contraception 
 
Exclusion criteria were: 
1. Subjects with diverticulosis 
2. Subject must not use protocol-defined prohibited medicines 
3. History of or current diagnosis of cardiovascular ischemic disease (e.g., angina 
pectoris, myocardial infarction, transient ischemic attack or stroke and including 
findings suggestive of ischemia on an ECG such as changes in ST segment and T 
waves, and / or Q wave) 
4. Clinical evidence of significant (as judged by the investigator) respiratory, 
cardiovascular, renal, hepatic-biliary, endocrine, psychiatric or neurologic 
diseases or presence of abdominal adhesions 
5. Presence of pacemakers 
6. History of or current eating disorder such as anorexia or bulimia or compulsory 
overeating. 
7. Diagnosis of mega-rectum or colon, a history of intestinal obstruction, congenital 
anorectal malformation, clinically significant rectocele, or any evidence of 
intestinal structural abnormality including gastrointestinal resection that affected 
bowel transit or any evidence of intestinal carcinoma, of inflammatory bowel 
disease or of alarm symptoms such as weight loss, rectal bleeding, or anemia. 
8. Actively participating in another clinical trial 
 
Intervention 
Subjects underwent a 2-week run-in period where they were instructed to stop all 
laxatives. The capsule was activated and started vibrating 8 hours after administration. 
Each subject received 2 capsules per week and completed a daily bowel movement and 
laxative use questionnaire. On each follow-up visit, expelled capsules were collected, and 
side effects were recorded.    
All capsules were collected from the stool to insure safety. 
 
Results   
Twenty-eight subjects were recruited into the study and 26 completed it (the two 
dropouts were not interested in participating in the study anymore. The reason for 
dropout was the difficulty in the study design. Subjects had to collect each capsule from 
their stool and bring it back to the study coordinator). Fourteen of those who completed 

 
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the study had IBS-C and 12 had functional constipation. The mean age of the 26 subjects 
who completed the study was 47.0 ±12.6 years (range 19–65).  The majority of subjects 
(25/26) were female, as expected in a constipation clinical trial. 
 
 
 
Age (years) 
Height (cm) 
Weight (kg) 
N 
28 
28 
28 
Mean 
47.0 
165.0 
63.8 
Std 
12.6 
5.4 
10.5 
Min 
19.0 
156.0 
47.0 
Median 51.5 
165.0 
63.0 
Max 
65.0 
175.0 
100.0 
 
 
N 
% 
Gender 
3 
10.7 
Male 
Female 
25 
89.3 
Ethnicity 
28 
100.0 
 
Safety results 
There were no problems with evacuation of the capsule in any subject. Of the 26 subjects 
who completed the study, 12 reported AEs. In all, 27 AEs were observed in these 12 
subjects, none of them serious. Nine of the 27 AEs may potentially have been related to 
the study. They were: 
- 
Abdominal pain: 3 subjects (11.1%), 5 events 
- 
Diarrhea: 2 subjects (7.7%), 2 events 
- 
Flatulence: 2 subjects (7.7%), 2 events. 
 
 
All adverse events were mild, and all were resolved without any action taken. Events of 
flatulence lasted 7 and 15 days.  One event of abdominal pain (stomach ache) lasted one 
day. All other events were resolved within the day. 
 
Efficacy results  
There was a significant increase in the mean number of SBMs/week for the entire study 
population. The increase in the mean number of SBMs/week for the entire study 
population was 1.60 ± 1.09, from 2.19 ±0.67 to 3.79 ± 1.31 (p < 0.001). The mean 
number of weekly SBMs increased from baseline in 23 of the 26 subjects (88.5%).   
In sub-group analyses by etiology of constipation, the mean increase in SBM was 1.46 ± 
1.08 (p = 0.001) for subjects having IBS-C and 1.75 ± 1.14 (p = 0.001) for subjects with 

 
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functional constipation. For the entire study population and for the two sub-groups, each 
weekly mean SBM was higher than the mean at baseline. 
 
 
 
Phase 3 clinical investigation 
 
The purpose of the investigation was to evaluate the efficacy and safety of the Vibrant 
Capsule compared to a sham non-vibrating capsule on spontaneous bowel movements. 
The study was a multinational, multicenter, prospective, randomized, double-blind, sham 
controlled trial. Identical capsules were used in the sham arm, eliminating only the 
activation of the capsule in the large intestine, for the sham group.  
The protocol provided for enrollment of 158 subjects in the US and Israel, to ensure at 
least 144 evaluable subjects, accounting for up to 10% drop-out.  The subjects were 
randomized in a 1:1 ratio.  
Eligible consented subjects were randomized to the active medical device (vibrating 
capsules) or to sham (non-vibrating capsules). The first two weeks were considered the 
run-in period, during which no use of constipation medication was allowed. Following 
the run-in period, subjects ingested two capsules per week for 8 weeks of treatment, 1 
every 3 days (±1). Subjects were evaluated by the Principal Investigator at the site. 
Following the completion of 8 weeks, subjects continued to be evaluated for an additional 
2 weeks with no treatment (wash-out). Subjects were instructed to complete a simple 
subject diary throughout the duration of the study to include daily recording of number 
and time of bowel movements, complete/incomplete evacuation, straining using a VAS 
scale, and evaluation of abdominal pain. 
Study duration was 2 weeks of run-in, followed by 8 weeks of treatment, followed by 2 
weeks of follow-up (wash-out) with no treatment, for a total of 12 weeks. 
 
Inclusion and exclusion criteria 
Inclusion criteria 
1. 
Subjects aged 18 years and older.  
2. 
Subjects with chronic idiopathic constipation according to Rome III criteria 
and who have not experienced relief of their symptoms from available 
therapies (osmotic and stimulant laxatives which was used for at least one 
month at recommended dose).  
3. 
Subjects with more than 1 bowel movement/2 weeks and < 3 bowel 
movement/week.  
4. 
Colonoscopy performed in the past 10 years prior to study participation, 
unless the subjects are <50 years old and without alarming signs and 
symptoms  
5. 
Subject signed the informed consent form    
6. 
For women with childbearing potential, adequate contraception 
 
Exclusion criteria 

 
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1. 
History of complicated/obstructive diverticular disease 
2. 
History of intestinal or colonic obstruction. 
3. 
History of significant GI disorder.  
4. 
Use of following medication: Medication that may affect the bowel 
mobility, Prokinetics, Anti-Depressants, medications for treatment of 
Parkinson 
disease, 
Opiates, 
Calcium-channel 
Blockers, 
Aluminum/Magnesium Hydroxids 
5. 
Clinical evidence of significant respiratory, CVS, renal, hepatic, biliary, 
endocrine, psychiatric, neurologic, or presence of abdominal pacemakers. 
6. 
Presence of pacemaker. 
7. 
History of, or current eating disorders, such as anorexia, bulimia, or 
compulsory overeating. 
8. 
Diagnosis of mega-rectum or colon, a history of intestinal obstruction, 
congenital anorectal malformation, clinically significant rectocele, or any 
evidence of intestinal structural abnormality, including GI resection that 
affects bowel transit, or any evidence of intestinal carcinoma or 
inflammatory bowel disease of alarm symptoms such as weight loss, rectal 
bleeding, or anemia. 
9. 
History of Zenker’s diverticulum, dysphagia or a known esophageal 
stricture 
10. 
Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) 
11. 
Participation in another clinical study in the last 4 months prior to screening. 
12. 
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 clinical study. 
13. 
Women who are pregnant or lactating. 
 
Primary endpoints: 
The primary endpoints of the study were as follows: 
• Frequency of bowel movements – change from baseline in the weekly 
Spontaneous Bowel Movement (SBM) rate during treatment period. Success was 
defined as increase by at least 1 SBM/week. The primary analysis was a 
comparative analysis of success rates between the study groups.  
• Quality of life (QOL) – improvement was defined as an increase of ≥1 point. 
Analysis was a comparative analysis of QOL improvement rates as defined 
between the study groups. 
• Safety: No serious device related adverse effects. 
 
 
Results 
154 subjects were enrolled in the study, 77 in the Vibrant arm, 77 in the Sham arm, in 16 
centers (6 in Israel, 10 in the USA). 145 subjects (89%) were female, with a mean age of 
46.4±12.8 years old (range 19.7 – 76.5) and average BMI of 26.8±5.3. 
 

 
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Vibrant 
Sham 
Total 
Female 
73 (89.0%) 
72 (88.9%) 
145 
(89.0%) 
Male 
9 (11.0%) 
9 (11.1%) 
18 (11.0%) 
 
Safety analysis 
A summary of all gastrointestinal adverse events observed in the study by treatment 
group is provided in the table below.  A table with all adverse events, including non-
gastrointestinal events, is provided in Appendix B.  As shown in the table below, there 
were no statistically significant differences in adverse event rates between the Vibrant 
Capsule and sham groups with the exception of the sensation of vibration in the abdomen 
which was statistically significantly higher in the Vibrant Capsule group compared to the 
sham group, as shown below.  The rate of occurrence of bloating/flatulence was 
numerically but not statistically significantly higher in the sham group, and the rate of 
diarrhea was numerically but not statistically significantly higher in the Vibrant capsule 
group.  
In addition, no subject experienced adverse events related to the Vibrant Capsule that 
required discontinuation.  There were also no adverse events related to the Vibrant 
Capsule that were considered serious.  The only serious adverse events in the study were 
not related to the Vibrant Capsule (fractured nose and injured knee). 
 
 
Vibrant 
Sham 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Ŧ 
Number 
of 
Reports 
Number 
of 
Subjects 
Incidence 
Ŧ 
Fisher's 
exact 
test p-
value 
All 
252 
51 
62.20% 
183 
44 
54.32% 
0.3426 
Abdominal cramping 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Abdominal pain/cramping/discomfort 
27 
14 
17.07% 
21 
14 
17.28% 
1.0000 
Aggravation of constipation 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Allergy 
2 
2 
2.44% 
. 
. 
. 
0.4969 
Bloating and/or Flatulence 
31 
16 
19.51% 
52 
22 
27.16% 
0.2710 
Blood in stool 
1 
1 
1.22% 
2 
2 
2.47% 
0.6204 
Diarrhea 
15 
8 
9.76% 
3 
3 
3.70% 
0.2105 
Discomfort 
. 
. 
. 
2 
2 
2.47% 
0.2454 
Discomfort – indigestion 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Discomfort – stomach 
1 
1 
1.22% 
1 
1 
1.23% 
1.0000 
Emesis 
3 
3 
3.66% 
2 
2 
2.47% 
1.0000 
Emesis - induced by GERD 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Gagging on capsule 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Galactorrhea 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Gastroenteritis 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Hemorrhoids 
2 
2 
2.44% 
. 
. 
. 
0.4969 
Nausea 
18 
9 
10.98% 
8 
6 
7.41% 
0.5894 
Pain in belly button 
1 
1 
1.22% 
. 
. 
. 
1.0000 

 
VIBRATING CAPSULE 
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Vibrant 
Sham 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Ŧ 
Number 
of 
Reports 
Number 
of 
Subjects 
Incidence 
Ŧ 
Fisher's 
exact 
test p-
value 
Rectal bleeding 
3 
2 
2.44% 
. 
. 
. 
0.4969 
Rectal cramping / spasm 
12 
2 
2.44% 
. 
. 
. 
0.4969 
Sensation of burning - abdomen (right 
lower quadrant) 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Sensation of vibration in abdomen 
50 
14 
17.07% 
2 
2 
2.47% 
0.0027 
Stomach ache and/or cramp 
7 
5 
6.10% 
20 
6 
7.41% 
0.7657 
Ŧ The incidence is defined as the percent of subject’s reporting a specific AE at least once, out of the total 
number of subjects in that group. 
 
 
A summary of adverse events severity is provided below. 
 
  
  
Vibrant Group 
Sham Group 
Number 
of reports 
Number of 
subjects 
IncidenceŦ 
Number of 
reports 
Number of 
subjects 
IncidenceŦ 
Any Adverse Event 
252 
51 
62.20% 
183 
44 
54.32% 
Mild 
203 
42 
51.22% 
136 
34 
41.98% 
Moderate 
47 
21 
25.61% 
44 
18 
22.22% 
Severe 
1 
1 
1.22% 
1 
1 
1.23% 
Adverse Event Leading 
to Discontinuation 
0 
0 
0% 
0 
0 
0% 
Ŧ The incidence is defined as the percent of subject’s reporting a specific AE at least once, out of the total 
number of subjects in that group. 
 
Overall, safety results were highly favorable. No adverse event was found significantly 
more in the Vibrant group except sensations of vibration (without any association of 
discomfort or pain). There was no discontinuation of treatment and no serious adverse 
event related to the device. 
 
Efficacy analysis - overall population 
 
 
Primary Endpoints 
 
With respect to the first primary endpoint, the proportion of subjects who had an increase 
of at least 1 SBM/week for at least 6 out of 8 weeks, the data are presented in the Table 1 
below. 
 
 
Study Arm 
Vibrant 
Sham 
Total 
N 
% 
N 
% 
77 
45.45% 
77 
46.75% 

 
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      Table 1 
Although the proportion of responders was similar between the Vibrant Capsule and 
sham groups, the majority of the population, approximately 60%, showed some evidence 
of benefit from the Capsule with respect to the number of SBMs/week (increase of at 
least 0.5 SBM for 6 weeks out of 8). Table 2 and Figure 4 detail the weekly increase in 
number of SBM for both groups over the treatment period. The mean number of 
SBMs/week was increased from 2.0 during run-in to 3.5-4.3 SBMs/week throughout the 
8-week treatment period, and remained elevated during the washout period. Similar 
improvements were observed over time with respect to the median number of SBMs.  
In the Vibrant group, the maximum number of weekly SBM is reached in week 5 with 
4.3 SBM.  
 
 
# of SBM 
Study Arm as treated 
Vibrant 
Sham 
N Mean SD Min Median Max N Mean SD Min Median Max 
Run-in 
Baseline 
82 
2.0 0.9 0.0 
2.0 
5.5 79 
1.9 1.0 0.0 
2.0 
7.0 
Treatment 
Week 1 
77 
3.5 2.2 0.0 
3.0 10.0 79 
3.2 2.2 0.0 
3.0 12.0 
Week 2 
76 
3.7 2.2 0.0 
3.3 10.0 79 
3.5 2.6 0.0 
3.0 13.0 
Week 3 
74 
3.9 2.4 0.0 
3.0 15.0 78 
3.7 2.4 0.0 
3.0 11.0 
Week 4 
74 
4.1 3.1 0.0 
3.5 20.0 77 
3.8 2.7 0.0 
3.0 12.0 
Week 5 
73 
4.3 3.4 0.0 
4.0 15.0 74 
3.7 2.3 0.0 
4.0 10.0 
Week 6 
72 
4.1 3.3 0.0 
3.0 21.0 73 
3.9 2.6 0.0 
4.0 10.0 
Week 7 
71 
4.3 2.7 0.0 
4.0 13.0 72 
3.9 2.5 0.0 
4.0 14.0 
Week 8 
69 
3.8 2.8 0.0 
3.0 14.0 72 
3.7 2.8 0.0 
3.0 15.8 
Wash-out 
Post Tx 
73 
3.8 3.4 0.0 
3.3 22.6 76 
3.4 2.4 0.0 
3.4 12.9 
Table 2 
 
 
Figure 3. Number of weekly SBM during the treatment 
With respect to the second primary endpoint, Quality of Life, less than a third of the 
subjects in each group achieved a one-point improvement in QOL, as required for 
endpoint success.  As discussed with FDA during the planning of the investigation, 
significant improvement in QOL was not anticipated due to the generalized nature of 
many question on the PAC-QOL.  The PAC-QOL score is comprised of 28 items 
organized into 4 domains (worries and concerns, physical discomfort, psychosocial 
discomfort, and satisfaction).    
QOL Improvement of at least 1 point 
 
Study Arm 
Vibrant 
Sham 
Total 
N 
% 
N 
% 
77 
26.47% 
77 
32.88% 
Table 3 

 
VIBRATING CAPSULE 
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Although a significant improvement in QOL was not observed in the majority of subjects 
in either group, there was additional and consistent evidence of benefit based on the 
secondary endpoints that were evaluated, as discussed below.   
 
 
Secondary Endpoints 
 
The secondary endpoints included the change from baseline in weekly SBMs, as reported 
above; the time from first Vibrant Capsule intake to first SBM; use of rescue 
medications; and PAC-QOL change from baseline; the change from baseline in Bristol 
Stool Score. Additional endpoints included: functional symptoms of bloating, straining, 
abdominal gas, and abdominal pain. The results for the change from baseline in weekly 
SBMs is provided above.  Multiple secondary and additional endpoints with respect to 
the Bristol Stool Score and symptoms showed evidence of benefit, as discussed below.  
With respect to the time to first SBM, there was no significant difference between groups.  
There was also no significant difference between groups in the use of rescue medication 
or the change from baseline in the PAC-QOL score.  
 
Number of accumulative days with rescue therapy  
 
Use of rescue medication was authorized after 5 consecutive days without a bowel 
movement. Subjects were allowed to take, by order: a glycerin suppository, an enema, or 
a laxative/bisacodyl tablet. The number of subjects who took rescue medication during 
the study does not indicate how many days each subject took rescue medication during 
the treatment. In order to reflect best the quantity of rescue taken, the number of days 
each subject took rescue medication was accumulated. For example, if 3 subjects took 
rescue medication 5 times and 2 subjects took rescue medication only once, then the 
number of rescue days will be 3*5 + 2*1=17.  
The number of days with rescue medication, stratified by response to treatment, is 
detailed below (Table 4). Table 5 details the statistical tests (one for the Vibrant arm, one 
for the Sham arm) assessing whether the rescue usage between the responders and non-
responders (within the Vibrant arm, and within the sham arm, separately) was significant 
or not. 
Subjects from the Vibrant (and Sham) groups who were responders used significantly 
less rescue medication than subjects who were not responders (p<0.0001 for Vibrant 
group, p=0.0002 for Sham): in the Vibrant group, responders took a total of 40 days of 
rescue medication, and non-responders took a total of 272 days. 
This confirms that responders were positively affected by the Capsule and needed less 
medication use. 
 
 
  
Vibrant - Responder 
Sham - Responder 
Total accumulative  
rescue days 
  
No 
Yes 
No 
Yes 
Vibrant 
Sham 
Number of days with 
rescue medication 
272 
40 
316 
46 
312 
362 
Table 4 

 
VIBRATING CAPSULE 
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Least Squares Means 
Effect 
Study 
Arm as 
treated 
Estimate 
Standard 
Error 
DF 
t Value 
Pr > |t| 
Alpha 
Lower 
Upper 
grr 
Sham 
1.9974 
0.4607 
137 
4.34 
<.0001 
0.05 
1.0865 
2.9083 
grr 
Vibrant 
1.7112 
0.4497 
137 
3.80 
0.0002 
0.05 
0.8219 
2.6005 
Table 5 
When comparing the Vibrant and Sham groups, there was no overall significant 
difference in rescue usage (p=0.5626). 
 
Bristol Stool Scale 
 
 
The Bristol Stool Scale is a 7-point, validated scale used to define stool consistency; it 
has been proven to be a useful indicator of transit time13-15. The scale ranges from 1 
(hard, dried, small lumpy stool) which a very constipated subject is expected to have, to 7 
(liquid stool) which corresponds to diarrhea. The scale reflects the amount of time the 
stool spent in the large intestine. The scales 3 and 4 are considered normal. Subjects in 
the study are thus expected to have a Bristol Stool Scale at baseline of 1 or 2 on average. 
The Bristol Stool Scale was measured at screening and at the end of the baseline period. 
The score at the end of the baseline period was used as the reference.  
 
The subjects in the Vibrant group had an improvement in the Bristol score of 0.9, vs. 0.5 
in the sham group. The difference in improvement between the two groups is 0.4 and is 
close to significance (p=0.0629), indicating that the Vibrant Capsule improved transit. 
 
 
  
Study Arm as treated 
Kruskal-
Wallis p-
value 
Vibrant 
Sham 
N 
Mean 
SD 
Median 
N 
Mean 
SD 
Median 
Overall 
69 
0.9 
1.2 
1 
70 
0.5 
1 
0 
0.0629 
Table 6 
 
CIC Symptoms Based on Daily Diaries 
 
Additional endpoints such as bloating, abdominal pain, straining, and abdominal gas were 
recorded from the daily diaries.  The bloating change from baseline was statistically 
significantly improved for the Vibrant Capsule group compared to the sham, with a 
difference between the two groups of -1 point (p=0.0345), on a scale of 10. 
 
  
Study Arm as treated 
Kruskal-
Wallis p-
value 
Vibrant 
Sham 
N 
Mean 
SD 
Median 
N 
Mean 
SD 
Median 
Bloating 
65 
-1.8 
2.5 
-1.3 
59 
-0.8 
2 
-0.7 
0.0345 
Abdominal pain 
68 
-0.5 
1.8 
0 
63 
-0.9 
2.2 
0 
0.6591 
Straining 
68 
-2.3 
2.4 
-2 
63 
-1.5 
2.5 
-1.2 
0.0824 
Abdominal gas 
65 
-1.1 
2.1 
-0.8 
57 
-0.4 
1.9 
0 
0.1094 

 
VIBRATING CAPSULE 
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In addition, although they did not reach statistical significance, the improvements in 
straining (p=0.0824) and abdominal gas (p=0.1094) are indicative of a positive trend. 
 
It should be noted that the scores were not reported every day but only the days the 
subjects had a bowel movement. If the subject did not have a bowel movement, questions 
about clinical symptoms were not required to be answered.  If they did have a bowel 
movement, the scores were recorded on that day.  Thus, the individual symptom scores 
captured as secondary endpoints reflect the subject’s more immediate daily assessments 
compared to the PAC-QOL score reported above. 
 
 
Efficacy analysis – post hoc subgroup 
 
 
Primary endpoints 
 
Based on a preliminary post-hoc analysis of the data, it became clear that the study 
eligibility criteria based on SBMs allowed the enrollment of a wide range of subjects of 
varying severity. Based on a the observed placebo effect in the overall population, as 
discussed above, additional analysis was performed stratified by baseline severity, based 
on average SBMs/week at baseline.  The results of this analysis demonstrate that the 
appropriate population most likely to benefit from use of the Vibrant Capsule is those 
with moderate to severe constipation. This subgroup was defined according to severity 
at baseline calculated as the weekly average number of SBM. The subjects with ≥2.5 
SBMs per week at baseline may not have constipation of sufficient severity to show 
benefit, while those with one or less weekly SBMs at baseline may be too severe to 
achieve significant benefit over sham without additional interventions or more frequent 
administration of capsules.   
Based on subject severity of constipation, the three subgroups encompassing the entire 
population study, were defined as follows:  
- 
Subjects with very severe constipation: average weekly SBM <1.1 
- 
Subjects with moderate to severe constipation: average weekly SBM ≥1.1 and 
<2.5,  (50% of the subjects) 
- 
Subjects with mild constipation: average weekly SBM ≥2.5. 
 
The responder rate stratified by baseline severity in terms of the number of SBMs/week, 
for the best 6 weeks out of 8, is presented below. 
The subgroup of subjects with ≥1.1 and <2.5 SBMs at baseline represented half of the 
population (N=77).  This subgroup demonstrated a 12% increase in the responder rate 
(increase of at least 1 SBM/week) for the Vibrant Capsule (59.5%) compared to the 
control (47.5%). 
 
 

 
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Study Arm as treated 
Chi-Square 
p-value 
Vibrant 
Sham 
N n 
Response 
Rate 
N n 
Response 
Rate 
Subgroup 
77 35 
45.45% 
77 36 
46.75% 
0.8716 
Overall 
subjects with 2.5 or more SBM on average at baseline 
27 9 
33.33% 
20 9 
45.00% 
0.4159 
subjects between 1.1 (including) and 2.5 (not including) SBM on average at baseline 
37 22 
59.46% 
40 19 
47.50% 
0.2933 
subjects with less than 1.1 SBM on average at baseline 
13 4 
30.77% 
17 8 
47.06% 
0.3668 
Table 7 
 
Figure 4 
Results of the PAC-QOL endpoint did not show any significant difference between the 
groups, as in the overall population.  However, there is other clear evidence of benefit to 
subjects based on the results of the secondary endpoints discussed below. 
 
 
Secondary Endpoints 
 
In addition to the clinical benefit in the subgroup that was observed with respect to the 
average number of SBMs/week, several secondary and additional endpoints showed a 
statistically significant difference in favor of Vibrant for the same subgroup, as explained 
below, including the Bristol Stool Score, straining, bloating, and use of rescue 
medications.  
 
Bristol Stool Scale 
 
At the conclusion of the 8-week treatment, there was a significant difference of 0.6 in the 
Bristol Stool Scale for moderate and severe subjects (p=0.0237).  While the other groups 
(<1.1 or ≥2.5 SBMs/week) also showed some numerical advantage for the Vibrant 
Capsule (0.3 and 0.1 SBM/week increase), the effect was smaller. Subjects in the Vibrant 
Capsule group generally moved from stools characterized as very hard to pass to stools 
that were easier to pass according to the scale.   
For moderate to severe subjects, although both Vibrant and Sham arms showed 
improvement, the Vibrant group improved, on average, twice as much as the sham group, 
corresponding to 1.2 Bristol Scale grade levels compared to 0.6 for the sham group.  In 
addition, the median change in Bristol Score in the Vibrant Capsule group was 1.0, 
representing a full grade, compared to a median change of 0 in the sham group.   
The Bristol Stool Scale indicates that the Vibrant Capsule has an effect on transit time, 
consistent with the intended mechanism of action to affect colonic contractility.  
 
  
Study Arm as treated 
Kruskal-
Wallis p-
value 
Vibrant 
Sham 
Difference in Bristol Score 
Difference in Bristol Score 
N 
Mean 
SD 
Median 
N 
Mean 
SD 
Median 
Subjects with ≥2.5 SBM on average at 
baseline 
26 
0.6 
1.1 
0 
18 
0.7 
1 
1 
0.5595 

 
VIBRATING CAPSULE 
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Subjects with ≥1.1 and <2.5 SBM on 
average at baseline 
35 
1.2 
1.3 
1 
38 
0.6 
1.1 
0 
0.0237 
Subjects with <1.1 SBM on average at 
baseline 
8 
0.6 
0.8 
0.3 
14 
0.3 
0.9 
0 
0.2626 
Table 8 
 
Figure 5 
 
CIC Symptoms Based on Daily Diaries  
 
Straining 
 
As noted above, several of the key symptoms of CIC showed statistically significant and 
clinically meaningful improvements in the moderate to severe subgroup.  First, straining 
during stool passage was rated on a 10-point scale.  At the conclusion of the 8-week 
treatment, there was a significant difference of -1.6 for moderate and severe subjects 
(p=0.0072).  All subgroups showed at least a -1.5 point improvement; thus, no group was 
detrimentally affected by receipt of the Vibrant Capsule.  
The Vibrant Capsule group for moderate to severe constipation showed a 2.9-point 
improvement in the straining score at the end of treatment compared to baseline, while the 
sham group improved by 1.3 points; similar trends were observed in the median 
improvement (2.7 for the Vibrant Capsule compared to 1.1 for the sham). The mean 
between-group difference was statistically significant (p=0.0072).  
 
Difference in Straining 
Study Arm as treated 
Kruskal-
Wallis p-
value 
Vibrant 
Sham 
N 
Mean 
SD 
Median 
N 
Mean 
SD 
Median 
Subjects with ≥2.5 SBM on average 
at baseline 
25 
-1.6 
2.4 
-1.2 
19 
-1.3 
2.1 
-0.8 
0.8404 
Subjects with ≥1.1 and <2.5 SBM on 
average at baseline 
36 
-2.9 
2.4 
-2.7 
36 
-1.3 
2.4 
-1.1 
0.0072 
Subjects with <1.1 SBM on average 
at baseline 
7 
-1.5 
2.3 
-1 
8 
-3 
3 
-3 
0.3846 
Table 9 
 
Figure 6 
 
Bloating 
 
Bloating was evaluated using a 10-point scale.  
At the conclusion of the 8-week treatment, there was a significant difference of -1.5 for 
moderate and severe subjects (p=0.0031), a difference of -0.5 for the very constipated 
subjects and -0.3 for the very severe and mild subjects. 

 
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Again, the largest difference in the degree of improvement in the bloating score was with 
subjects with moderate to severe constipation, and data from the two other subgroups 
confirms that other subjects were not negatively impacted by the Vibrant Capsule.   
As shown in the table below, the average improvement in bloating was 2 points in the 
Vibrant Capsule group in moderate to severe constipated subjects, compared to 0.5 points 
in the sham group.  This difference of -1.5 points between the 2 groups was statistically 
significant (p=0.0031).  Similar trends were observed with respect to the median (1.7 
points for the Vibrant Capsule versus 0.3 points for the sham). 
 
Difference in Bloating 
Study Arm as treated 
Kruskal-
Wallis p-
value 
Vibrant 
Sham 
N 
Mean 
SD 
Median 
N 
Mean 
SD 
Median 
Subjects with ≥2.5 SBM on average at 
baseline 
24 
-1.5 
3.1 
-0.4 
18 
-1.2 
1.4 
-1 
0.5587 
Subjects with ≥1.1 and <2.5 SBM on 
average at baseline 
34 
-2 
2 
-1.7 
33 
-0.5 
2 
-0.3 
0.0031 
Subjects with <1.1 SBM on average at 
baseline 
7 
-2 
2.8 
-1.3 
8 
-1.5 
2.7 
-0.5 
0.5241 
Table 10 
 
 
Figure 7 
 
 
Conclusions Drawn from the Studies 
 
Total experience with the Vibrant Capsule in 109 actively treated subjects demonstrates 
that the Capsule is safe and well tolerated.  There were no cases of device discontinuation 
in any subject, and the rate of occurrence and severity of adverse events was similar for 
the Vibrant Capsule and the Sham.  No serious device-related adverse events were noted.   
 
In addition to the Capsule’s highly favorable safety profile, the majority of subjects in the 
overall population, approximately 60%, showed improvement in symptoms that was 
corroborated with the improvement of the SBM, providing clinically meaningful benefit 
for the subjects, with respect to the number of SBMs/week.  Several of the secondary 
endpoints reached significance or trended toward significance, including bloating 
(p=0.0345), the Bristol Stool Score (p=0.0629), straining (p=0.0824), and abdominal gas 
(p=0.1094).   
 
The subgroup that was identified as most likely to benefit from the Vibrant Capsule is 
those with moderate to severe constipation, defined as ≥1.1 and <2.5 SBMs/week.  The 
group with less than 1 SBM/week may have pathology too severe for the Vibrant Capsule 
to overcome with only 2 capsules/week, while the group with ≥2.5 SBMs/week may have 
a condition too mild to allow sufficient room for improvement according to the specified 
response criteria.  While none of the three subgroups were detrimentally affected by use 
of the Vibrant Capsule, the subgroup with moderate to severe CIC showed the greatest 

 
VIBRATING CAPSULE 
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benefit, with a clinically meaningful difference of 12% between the two groups and 
additional evidence of improvement on several secondary endpoints, including the Bristol 
Stool Scale, as well as symptom scores for bloating and straining based on daily diaries.  
The safety profile in the moderate to severe CIC subgroup was also highly favorable, as 
in the overall population. 
Based on the positive signal, the Sponsor has decided to increase the frequency of 
administration of the Vibrant Capsule and to confirm the positive results reported in the 
sub-cohort population. 
 
12. 
STUDY OBJECTIVE 
 
The objectives are to assess the efficacy and safety of the Vibrant capsule administered 2 
times per week. 
 
13. 
STUDY ENDPOINTS 
13.1 
Primary endpoint 
 
The two primary efficacy endpoints are the CSBM1 success rate, defined as 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 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. 
13.2 
Secondary endpoints 
 
Secondary efficacy endpoints include:  
- 
Change from baseline in average straining 
- 
Change from baseline in average stool consistency, using the Bristol Stool Scale 
- 
Change from baseline in average bloating. 
- 
SBM success rate, defined as as an increase from the run-in period of at least one 
weekly Spontaneous Bowel Movement (SBM) during at least 6 of the 8 weeks of 
treatment. Subjects with less than 2 weeks (with at least 5 days per week) of valid 
diary during the treatment period will be considered as non-evaluable. 
 
Additional effciacy endpoints 
- 
Change from baseline in weekly number of Spontaneous Bowel Movement 
(SBM). 

 
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- 
Change from baseline in weekly number of Complete Spontaneous Bowel 
Movement (CSBM). 
- 
Change from baseline in average abdominal gas. 
- 
Change from baseline in average abdominal pain. 
- 
Change from baseline in abdominal discomfort. 
- 
Time to occurrence of spontaneous bowel movement after capsule activation. 
- 
Treatment satisfaction score using the TSQM (Treatment Satisfaction 
Questionnaire for Medication) 
- 
Ease of use of the device 
Safety endpoints include all adverse events related and unrelated to the study treatment. 
 
14. 
STUDY CONDUCT & POPULATION  
 
This study will be performed in accordance with the design and specific provisions of this 
protocol , in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki, that are consistent with Good Clinical Practice (GCP), Title 21 of the Code of 
Federal Regulations (21 CFR), part 812 (Investigational Device Exemptions),  and the 
applicable regulatory requirements. 
 
14.1 
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 <3 Spontaneous Bowel Movements (SBM) per week 
and ≥1 SBM per week 
4. Normal colonoscopy performed within 10 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.  
 

 
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14.2 
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. 
History of gastroparesis 
5. 
Use of any of the following medications:  
o 
Medications that may affect intestinal motility, prokinetics, anti-
Parkinsonian medications, opiates, opioids, calcium-channel 
blockers, aluminum/magnesium hydroxide 
o 
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 symptoms and medication usage 
17. 
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. 
 

 
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14.3 
Duration of Study  
 
Study duration includes at least  2 consecutive weeks of run-in, followed by 8 weeks of 
treatment - Total of at least 10 weeks. 
The sample size is calculated for 66 subjects. 
 
15. 
STUDY TREATMENT 
Detailed study treatment herein: 
15.1 
Study Design 
 
The study is a prospective, multicenter, adaptive, randomized, double-blind, sham-
controlled pilot study to evaluate the efficacy and safety of  various vibrating modes. 
 
The objective is to assess the efficacy and safety of the Vibrant Capsule with a frequency 
of administration of 2 capsules per week. 
 
The study will be performed in up to 15 centers in the USA. 
 
Data reporting will be done on an electronic Case Report Form (eCRF). In addition, 
subjects will fill in daily information about their bowel movements, clinical symptoms 
and medication usage on an electronic Diary (eDiary). The eDiary will be accessed via a 
computer, smartphone, tablet or other suitable device, through a designated website.  
Information about time of activation of the Vibrant Capsules will be recorded 
automatically by the base unit and automatically transferred to a designated website. 
 
Subjects with Chronic Idiopathic Constipation (CIC) according to Rome III criteria who 
failed currently available therapy (defined as osmotic and stimulant laxatives used for at 
least one month at recommended dose) and meet the inclusion criteria will be offered 
participation in this study. The background of the proposed study and its risks and 
benefits will be explained to the subject and the informed consent form will be signed.  
 
Subjects will be screened for study eligibility according to inclusion and exclusion 
criteria. The daily bowel movements frequency, history of constipation, etiology of 
constipation and medication use (including prescription medication) will be throroughly 
assessed. Subject demographic and medical information acquired from the subject or the 
subject's medical chart, including age, gender, previous medical history, risk factors etc. 
will be also recorded on the eCRF.  
In addition, subjects will undergo a physical examination including digital rectal 
examination, vital sign measurements and blood tests.  
 

 
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Subjects will then fill in the the Rome III questionnaire to confirm the diagnosis of 
Chronic Idiopathic Constipation and fill out the Bristol Stool Scale questionnaire.  
Findings will be recorded on the eCRF. 
 
Eligible subjects will then be asked to refrain from taking any medication or supplement 
they are using to relieve their constipation, and will perform a daily self-assessment of 
their normal spontaneous bowel movements for 14 consecutive days  (run-in period), 
utilizing the eDiary. Subjects will also be asked to record clinical symptoms and usage of 
any medication or supplement on the eDiary during the run-in period.  
 
After the run-in period the subjects will visit the medical center for the baseline visit. 
Eligibility will be re-assessed and confirmed based on the subject's completed eDiary and 
Rome III questionnaire. The subject will be trained in the medical center to use the base 
unit. He will activate himself the first capsule and will ingest it in front of the medical 
staff. All the other capsules will be ingested from the home of the subject. Only the first 
ingestion will take place in the medical center.  
During the treatment period, subjects will ingest Vibrant Capsule 2 days per week: one 
capsule on Mondays and one capsule on Thursdays. Subject will not ingest any capsule 
on Tuesdays,Wednesdays, Fridays, Saturdays and Sundays. The subject will ingest a total 
of 16 capsules in 8 weeks considering the sequence. 
If the baseline visit falls on a Thursday or Wednesday or Friday or Saturday, the subject 
should ingest the first capsule on site.  
 
NOTE: 
In order to compensate; 
• 
if the baseline visit is on a Tuesday, the second capsule taken should be on Thursday as 
planned.  
• 
if the visit is on Wednesday, the second capsule taken should be the next Monday.  
• 
If the baseline visit is on Friday, the next capsule taken should be on the next Monday as 
planned. 
Following this the subject should follow the normal schedule. 
 
Capsule intake will ideally be performed during the evening, between 9 PM and 10 PM 
(except on days where a capsule is ingested on site). 
 
The subjects will be asked to refrain from taking any medication or supplement they are 
using to relieve their constipation until they complete the study.  
After 8 weeks, treatment will be ceased and subjects will visit the medical center one last 
time for evaluation and completion of Rome III questionnaire and other assessments.   
 
Subjects will be instructed to complete a simple subject eDiary throughout the duration of 
the study. This will include daily recordings of capsule intake, number and time of bowel 
movements, clinical symptoms, satisfaction score and medication/supplements usage, 
including rescue medication. 
 

 
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Please refer to section 15.15 for a detailed study schedule. 
 
Data collection will include physician identification, investigational device identification 
data and usage of the capsule. This data will be documented on the eCRF, together with 
the occurrence of any adverse events during the capsule usage. 
 
All subject adverse events (whether device related or not) will be recorded during the 
course of the clinical study. All serious adverse events/complications will be reported 
immediately (within 24 hours) to the study sponsor/monitor and to the Institutional 
Review Board. 
 
15.2 
Medical History 
Subject demographic and medical information acquired from the subject or the subject's 
medical chart, including age, gender, weight, height, body mass index (BMI), number of 
natural childbirth and previous medical history and medications will be recorded, 
including: a history of clinically significant abnormalities of all body systems; concurrent 
diseases; relevant past medical history.  
The information will be recorded in the eCRF for all subjects participating in this study.  
15.3 
Constipation History 
Full history of constipation will be recorded on the eCRF, including duration of 
constipation, full history and habits of medication (over the counter and prescription) and 
supplements use, frequency of spontaneous bowel, current medication/supplements use, 
description of current diet (with focus on water intake and fiber intake), physical activity 
(number of hours of physical activity per week), recent change in bowel movements. 
15.4 
Physical Examination 
During the screening visit all subjects will undergo a conventional physical examination 
by an authorized physician. The physical examination will include diagnosis and 
documentation of any significant abnormalities or diseases. The physical examination 
will include a digital rectal examination. 
15.5 
Assessment of pelvic floor dysfunction (defecatory 
disorder) 
Assessment of pelvic floor dysfunction will be based on subject history. Subjects with 
suspicion of pelvic floor dysfunction will be excluded. 
If subjects have been previously diagnosed with pelvic floor dysfunction following 
anorectal manometry, a balloon expulsion test, or other examinations, documented results 
from these tests can be used to exclude subjects.   
 

 
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15.6 
Blood and urine tests 
During the screening visit all subjects will undergo the following blood tests: blood 
count, calcium, creatinine, Blood Urea Nitrogen (BUN), sodium, potassium and TSH. 
Blood pregnancy test will be performed during the screening visit. A pregnancy urine test 
will be performed during the baseline visit. 
15.7 
Screening visit (day -21 to -14) 
At the screening visit, subjects will be evaluated for eligibility and undergo physical 
examination, digital rectal examination, vital sign measurements and blood tests. They 
will undergo a thorough interview about their constipation and the Rome III 
questionnaire (see appendix C) will be completed. The Bristol Stool Scale (see Appendix 
A) will also be completed by the subject.  
 
The investigator will confirm their eligibility and their physical and mental suitability to 
participate in this study.  
Subjects exiting the trial at this stage will be considered screening failure subjects and be 
replaced with new subjects. 
 
The subject will be trained by the study coordinator to access and use the eDiary.  
The eDiary contains questions about bowel movements and their associated clinical 
symptoms (straining, abdominal pain, abdominal discomfort, abdominal gas, bloating, 
need for digital maneuver, sensation of complete evacuation), usage of rescue medication 
and usage of other medication or supplements (name of drug, dosage, number of takes 
per day, reason for medication).  
The information will be transferred to the eCRF every day.  
 
The subject will define his/her preferred device to use the eDiary. The subject and study 
coordinator will define together the time of the day during which the subject will fill in 
the eDiary and a daily alert will be set up on the phone of the subject. The daily diary can 
be found in Appendix F. 
  
15.8 
Run-in period (day -21 to -14, to -1) 
Eligible subjects will be observed and monitored for the first 2 weeks, in which they will 
be asked to refrain from taking any medication or supplement to relieve their 
constipation.  
The run-in period may be extended by a few days in case of technical issue (difficulty to 
access eDiary), to allow for a wash-out period, or other. The run-in period may be 
extended by up to 7 days. 
Subjects will complete the eDiary every day and there should be a period of at least 14 
consecutive days between the first day the subject fills in the diary and the last day of 
run-in period. 14 consecutive days of the eDiary will be monitored to determine 
eligibility of the subjects. 

 
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On the day of screening, the coordinator should determine with the subject the last day of 
intake of constipation medication/aid and ensure that the last intake of constipation 
medication/aid has been taken more than 48 hours before the first diary entry. 
 
The subjects will receive at least 1 short phone call/week from the study coordinator, 
more if needed.  
The phone calls will be about 5-10 minutes long and will ask check subject compliance 
with the eDiary, occurrence of adverse events, use of rescue medication, subject 
understanding of what he needs to do in the context of the study and discuss any issue or 
difficulty that the subject might have. Confirmation of date and time of the phone call 
will be reported on the eCRF. 
 
If a subject does not fill in his/her eDiary, the sponsor/investigator will be alerted and the 
subject will be contacted by phone call in order to receive more information and gather 
the missing information. Compliance of the subject will be closely monitored. 
Subjects who fail to fill in their diary 3 times or more (not due to technical issues) during 
the run-in period will be considered as screening failures due to lack of compliance. 
15.9 
Treatment 
On day 0 (baseline visit), the subject will arrive to the clinic. Eligibility will be re-
assessed and confirmed based on the Rome III questionnaire and on the subject's 
completed diary. Subjects need to have an average of at least 1 SBM per week but less 
than 3 SBM per week during the two weeks of run-in. They must have at least 1 SBM per 
week for each of the 2 weeks of run-in.  
 
Eligible subjects will be randomized to: 
- 
Vibrant arm – vibrating mode 1, with a frequency of administration of 2 capsules 
per week, OR 
- 
Vibrant arm – vibrating mode 2, with a frequency of administration of 2 capsules 
per week, OR 
- 
Sham arm, with a frequency of administration of 2 capsules per week. 
 
Treatment duration is 8 weeks. 
The subject will be trained by the study coordinator to use the base unit and activate the 
capsules. After an oral explanation, the subject will read the base unit user manual, and 
the study coordinator will make sure the subject fully understands how to use the base 
unit. The subject will then activate the first capsule, in front of the study coordinator, and 
swallow it.  
The subject will then be released home with the base unit and capsules for the first two 
weeks of treatment. The subject will be asked to continue with the daily completion of 
the eDiary. 
Actual point of enrollment for the subject is considered the day of first capsule intake. 
 

 
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Subjects will be asked to refrain from any medication or supplement they are using to 
relieve their constipation, throughout the treatment period. A rescue treatment will be 
authorized upon need (refer to section 15.10 for details).  
 
Capsule intake should take place ideally during the evening between 9 PM and 10 PM, on 
Mondays, and Thursdays.  
The first intake, which will take place in the medical center during the day, will not 
follow these rules.  
 
Capsule distribution for the subject will be in 3 time points: 
- 
Day 0 (baseline visit): capsules for 2 weeks of treatment will be provided 
- 
Day 14 ± 2 days (treatment visit 1): capsules for 3 weeks of treatment will be 
provided 
- 
Day 35 ± 2 days (treatment visit 2): capsules for 3 weeks of treatment will be 
provided. 
 
The subjects will receive at least one phone call per week from the study coordinator.  
The phone calls will be about 5-10 minutes long and will check subject compliance with 
capsule ingestion and the eDiary, occurrence of adverse events, use of rescue medication, 
subject understanding of what he/she needs to do in the context of the study and discuss 
any issue or difficulty that the subject might have. Confirmation of date and time of the 
phone call will be reported on the eCRF. 
Compliance of the subject will be closely monitored.  
 
Overall the subject will visit the site twice during the treatment period: a first time 2 
weeks after the baseline visit, and a second time 3 weeks after that. The last visit will be 
the termination visit. The subject will receive the capsules in 3 separate visits: 
- 
Baseline visit: 4 capsules for 2 weeks of treatment (2 capsules for each week). 
- 
Visit 1 during treatment period: 6 capsules for 3 weeks of treatment (2 capsules for 
each week). 
- 
Visit 2 during treatment period: 6 capsules for 3 weeks of treatment (2 capsules for 
each week). 
The subject will receive spare capsules and must bring back to the site all remaining 
capsules in his/her possession for each visit. The capsules must be counted and accounted 
for. 
During each visit, an interview will be conducted, where the following topics will be 
discussed: occurrence of adverse events, compliance to filling in the daily information on 
the eDiary and to the treatment, concomitant medication/rescue taken, evolution of 
constipation symptoms, subject’s perceptions about the treatment, motivation of the 
subject, or any other topic relevant.  
 
 
15.10 
Rescue Treatment 
 

 
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Subjects will stop using all medication or supplement to relieve constipation during the 
entire study period and comply to use constipation aid only for rescue.  
Using one rescue medication is authorized only after 3 consecutive days without a bowel 
movement and under the rules described below. The subjects will not be required to 
contact the investigator prior to taking any medication/supplement but they will be 
required to declare all the rescue medication on their eDiary. The following treatment is 
recommended (not by order): 
1. Dulcolax® suppository/bisacodyl suppository 
2. Fleet Enema® 
3. Dulcolax®/bisacodyl tablet (1x5mg) 
 
The subject is allowed to take a rescue medication/supplement that is not in the above 
list, without contacting the investigator. The subject must declare all rescue intake in the 
eDiary. 
In a situation where the investigator prescribes a rescue medication/supplement that is not 
in the above list, the investigator will need to mention it and give the reason in a note to 
file or appropriate form. 
 
Subjects who take rescue medication three times or more during the run-in period will be 
considered as screening failures. 
 
A spontaneous bowel movement is defined as a bowel movement that occurs at least 48h 
after laxative/rescue intake and without digital maneuver. 
A complete spontaneous bowel movement is defined as a spontaneous bowel movement 
associated with a feeling of complete evacuation by the subject. 
 
15.11 
Termination visit 
After 8 weeks, treatment will be ceased. Subjects will visit again the medical center for 
evaluation and completion of the TSQM (Treatment Satisfaction Questionnaire for 
Medication)16, an ease of use questionnaire, the termination form and end of study form. 
The subject will be evaluated for occurrence of adverse events, concomitant 
medication/rescue and compliance to the eDiary and treatment. 
The subjects will bring back all remaining capsules in their possession as well as the base 
unit. The capsules must be counted and accounted for. 
 
The TSQM and ease of use questionnaires can be found in Appendix D and E 
respectively. 
15.12 
Concomitant medication 
All medication taken by the subject in addition to the investigational device is termed 
concomitant medication.  All concomitant medication taken during the study must be 
documented in the case report form (name of drug, date of intake, dosage, number of 
takes per day, reason for medication). The subject will fill in all the information daily on 
the eDiary.  

 
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15.13 
Prohibited medication 
The medications listed below will be prohibited during the entire study:  
- 
Medications that may affect intestinal motility  
- 
Prokinetics 
- 
Anti-Parkinsonian medications 
- 
Opiates 
- 
Opioids 
- 
Calcium-channel blockers 
- 
Aluminum/magnesium hydroxide. 
 
Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is also prohibited. 
Chronic use is defined as taking full dose NSAIDs on a regular basis (i.e. more than three 
times a week) for at least six months.  
Subjects on cardiac doses of aspirin may be enrolled in the study.  
 
The following medications are equally prohibited, but with an exception when the subject 
has been on a stable dose of the medication for at least 3 months: 
- 
Antidepressants 
- 
Thyroid or hormonal replacement therapy. 
 
15.14 
Recording 
All tests will be performed prior to procedure in case where not already done per routine 
hospital protocol. Device handling and function will be recorded.  
The standard treatment and care provided to all subjects, alongside the Vibrant capsule 
and other treatments will be performed and recorded on the appropriate study eCRF.  
The subject will be questioned on his clinical status, the presence of any medical 
intervention performed since the last visit and any adverse events or discomforts. When 
necessary, the subject will be asked to arrive for a follow-up visit at the clinic. 
15.15 
Study Schedule   
Table 11 summarizes the required data collection from assessments and tests performed 
during the study. 
 
Procedures 
Screening 
Baseline 
Treatment 
visit 1 
Treatment 
visit 2 
Termination 
visit 
Visit No. 
1 
2 
3 
4 
5 
Day 
-21 to -14 
0 
14 (±2 days) 
35 (±2 days) 
56 (±2 days) 
IC 
+ 
 
 
 
 
Eligibility Criteria 
+ 
+ 
 
 
 
Physical Exam 
+ 
 
 
 
 
Digital Rectal Exam 
+ 
 
 
 
 

 
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Vital Signs 
+ 
 
 
 
 
Lab Data 
+ 
 
 
 
 
Urine Pregnancy test (if 
applicable) 
 
+ 
 
 
 
Administration of 
capsule 
 
+ 
 
 
 
Rome III 
+ 
+ 
 
 
 
Bristol Stool 
+ 
 
 
 
 
TSQM & ease of use 
 
 
 
 
+ 
Subject eDiary 
+ 
+ 
+ 
+ 
+ 
Adverse Events 
+ 
+ 
+ 
+ 
+ 
Concomitant Medication 
+ 
+ 
+ 
+ 
+ 
Table 11 – Study Schedule of Assessments 
 
15.16 
Deviations from study protocol 
 
Any deviation from the study protocol should be notified to the sponsor, documented on 
study deviation forms and reported to the Ethics Committee as required. 
 
Protocol deviations related to treatment compliance (e.g. missed capsule, capsule taken 
on a Wednesday or Sunday, etc.) will not be declared on the protocol deviation form 
accessible via the EDC (Electronic Data Capture). Protocol deviations related to 
treatment compliance will be monitored and declared by the Sponsor, CRO and sites 
using a platform external to the EDC. This external platform will use the information 
transmitted from the base units about activations (base unit serial number, date and time 
of activation, success/failure) as a basis to monitor treatment compliance. 
Additional information transmitted by the subject from the eDiary about number of 
capsules taken out of the blister and swallowed for each day, as well as direct information 
given by the subject to the study coordinator by phone, email or SMS, will be used by the 
Sponsor and CRO to make a final decision about treatment compliance, for each day of 
treatment, for all subjects. 
A final list of protocol deviations related to treatment compliance will be issued at the 
end of the study, from the external platform, and signed. This list will be considered 
equivalent as protocol deviations forms. The site will not manually enter these protocol 
deviations in the EDC. 
 
15.17 
Investigative Center Selection Criteria 
 

 
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The investigative site will meet the following selection criteria prior to inclusion in this 
study: 
• Clinical research study experience and resources that demonstrate good 
compliance with study requirements and timely, complete documentation of 
subject follow-up.   
• Sufficient subject volume to meet enrollment timeframe. 
16. 
ADVERSE EVENTS RECORDING 
 
At each evaluation, the investigator will determine whether any adverse events (AE’s) 
have occurred. All adverse events occurring during the study will be recorded on the 
appropriate case report form page by the investigator.  The nature, severity and relation of 
the adverse event to the study device will be documented. 
16.1 
Reporting Requirements 
Timely and complete reporting of Adverse Events (AE) and safety assessment allows: 
• Protection of safety and study subjects. 
• Greater understanding of the overall safety profile of the study treatment. 
• Appropriate modification of study protocols and improvement in study design and 
procedures. 
• Adherence to regulatory requirements. 
The definitions and reporting requirements adopted in this study are derived from the 
current International standard on clinical investigations: Title 21 of the Code of Federal 
Regulations (21 CFR), part 312 (Investigational New Drug Application), Section 32 
(IND Safety Reporting) and part 812 (Investigational Device Exemptions), Section 150 
(Reports). 
16.2 
Definitions  
Adverse Events (AE) 
AE is defined as any untoward medical occurrence in a subject. This definition does not 
imply that there is a relationship between the adverse event and the device under 
investigation.  An AE can therefore be any unintended sign, symptom, disease or injury 
or any untoward clinical signs (including an abnormal laboratory findings) in subjects, 
users or other persons whether or not related to the investigational medical device. The 
following should be reported as AE: 
• Untoward medical conditions or signs or symptoms that were absent before 
starting study treatment. 
• Untoward medical conditions or signs or symptoms present before starting study 
treatment and worsen (increase severity or frequency) after starting study 
treatment. 
• Abnormal laboratory findings. 
• Clinical signs or symptoms that require therapy. 
 

 
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Device Deficiency  
Device Deficiency is defined as Inadequacy of a medical device related to its identity, 
quality, durability, reliability, safety or performance, such as malfunction, misuse or use 
error and inadequate labeling. 
 
Adverse Device Effect (ADE) 
ADE is adverse event, related to the use of an investigational medical device. This 
includes any adverse event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device, the operation, or any malfunction of 
the investigational medical device, device failure or misuse, and any event that is a result 
of a user error. 
 
Device failures, Malfunctions and Misuse 
Investigators are instructed to report all possible device failures or misuse observed 
during the course of the trial. These incidents will be documented in the case report form 
provided as follows: 
 
• Device Failure - A device failure has occurred when the device is used in 
compliance with the Instructions for Use, but does not perform as described in the 
Instructions for Use. A device failure occurs when  
o A capsule fails to activate.  
o The transmission about the first capsule activation cannot be performed 
(during the baseline visit) by the base unit. This event must lead to the 
replacement of the base unit.  
o The base unit loses its ability to transmit information permanently. This 
event must lead to the replacement of the base unit. 
Device Misuse - Any use of the investigational device by an investigator or 
subject that is contradictory to the application described in the Instructions for 
Use will be categorized as device misuse.  
 
 
Serious Adverse Events (SAE) 
A SAE is an adverse event that: 
1.     Led to a death, 
2.     Led to a serious deterioration in the health of the subject that: 
a. Resulted in a life-threatening illness or injury 
b. Resulted in a permanent impairment of a body structure or a body function 
c. Required in-subject hospitalization or prolongation of existing 
hospitalization  
d. Resulted in medical or surgical intervention to prevent permanent 
impairment to body structure or a body function. 
  3.    Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 

 
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Device deficiencies that might have led to a SAE if a suitable action had not been taken 
or intervention had not been made or if circumstances had been less opportune are also 
handled under the SAE reporting system.  
However, planned hospitalization for pre-existing condition and/or procedure required by 
the clinical trial protocol, without serious deterioration in health, is not considered to be a 
SAE. 
 
Serious Adverse Device Effect (SADE) 
A Serious Adverse Device Effect is an adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event. 
 
Unanticipated Serious Adverse Device Effect (USADE) 
USADE is defined as serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the current version of the risk analysis 
report or other study related documents.  
 
16.3 
Anticipated Adverse Events 
The Vibrant Capsule targets pathophysiological parameters of chronic constipation by 
inducing natural bowel activity without using chemical supplements. 
Anticipated Adverse Events include those that are reasonably expected to occur in 
association with a clinical investigation assessing a treatment for functional constipation. 
Events can occur as a result of the disease or as a result of the treatment (including usage 
of the home base unit). They may include but are not limited to the following (in 
alphabetical order): 
• 
Abdominal pain/discomfort/cramping 
• 
Blood in the stool may develop or increase 
• 
Bloating/Flatulence 
• 
Diarrhea  
• 
Nausea may develop or increase 
• 
Rectal pain may develop or increase 
• 
Sensation of vibration in the abdomen 
• 
Uncontrolled leakage of stool may occur 
• 
Vomiting may develop 
 
All events listed above, and additional events that the investigator will evaluate will fit 
the definition of ‘anticipated event’, will be categorized as such in the study. 
16.4 
Adverse Event Reporting 
All adverse events and adverse device effects occurring during the clinical trial must be 
recorded by the investigator on the appropriate AE form in the eCRF, within a reasonable 
time (up to 5 calendar days from investigator's awareness of the event). All AEs will be 
characterized by the following criteria: 
• Intensity or Severity 

 
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• Relatedness 
• Outcome 
• Treatment or Action Taken. 
 
16.4.1 
Intensity or Severity 
The following categories of the intensity of an adverse event are to be used:  
Mild – Awareness of a sign or symptom that does not interfere with the subject’s usual 
activity or is transient, resolved without treatment and with no sequelae. 
Moderate – Interferes with the subject’s usual activity and/or requires symptomatic 
treatment. 
Severe – Symptom(s) causing severe discomfort and significant impact of the subject’s 
usual activity and requires treatment. 
16.4.2 
Relatedness 
The investigator will use the following definitions to assess the relationship of the AE to 
the investigational medical device: 
Not related - The cause of the AE is known and the event is not related to the 
investigational medical device. 
Possibly related - There is a reasonable possibility that the event may have been caused 
by the investigational medical device. 
The AE has a timely relationship to the study procedure(s); however, follows no known 
pattern of response, and an alternative cause seems more likely or there is significant 
uncertainty about the cause of the event.  
Probably related - It is likely that the event was caused by the investigational medical 
device. 
The AE has a timely relationship to the study procedure(s) and follows a known pattern 
of response; a potential alternative cause, however, may explain the event. 
Related - A related event has a strong temporal relationship and an alternative cause is 
unlikely. 
 
16.4.3 
Outcome 
The clinical outcome of the AE or SAE will be characterized as follows: 
Death - The SAE CRF must be completed for this outcome (see 16.5 Expedited 
Reporting of Serious Adverse Events). 
Recovered without sequelae - The subject returned to baseline status 
Ongoing - Subject did not recover and symptoms continue 
Recovered with sequelae - The subject has recovered but with clinical sequelae from the 
event 
Unknown - The subject outcome is unknown 
 

 
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16.4.4 
Treatment or Action taken 
The treatment or action taken after the occurrence of an AE or SAE will be reported as: 
Interventional Treatment - Surgical, percutaneous or other procedure 
Medical Treatment - Medication frequency of administration reduction/interruption or 
discontinuation, or medication initiated for event 
None - No action is taken 
 
16.5 
Expedited Reporting of Serious Adverse Events 
Any Serious Adverse Event, and device deficiencies should be reported to Vibrant Ltd. 
within 24 hours of investigators' knowledge of the event. Investigator should report these 
events on the appropriate SAE form / Device Deficiencies Form in the eCRF and send 
the form by fax or e-mail, to the following safety contact person: 
 
Lior Ben Tsur 
Vibrant 
Hakochav 
Yokneam 2069206 
P.O.Box 516, Israel 
Tel: +972-46-663322 
Cell: + 972-54-6950001 
Lior.b@vibrantgastro.com 
 
If applicable, the investigator should also inform the representative of the appropriate 
local Ethics Committee, within 24 hours of investigator's awareness of the event. A copy 
of the report cover letter should be filed within the study file.  
  
The sponsor is responsible for the ongoing safety evaluation of the investigational 
medical device. The sponsor will promptly notify all concerned 
investigator(s)/institution(s) and the regulatory authority(ies) of findings that could affect 
adversely the safety of subjects, impact the conduct of the trial, or alter the Medical 
Ethics Committee approval/favorable opinion to continue the trial. 
 
The sponsor will expedite the reporting to all concerned investigator(s)/institutions(s), to 
the EC(s), where required, and to the regulatory authority(ies) of the occurrence of 
Unanticipated Serious Adverse Device Effects.  
 
16.6 
Follow- Up of Unresolved Events 
All adverse events should be followed until they are resolved or the subject’s 
participation in the study ends.  

 
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17. 
STATISTICAL CONSIDERATIONS  
17.1 
Study Design and Objectives 
 
The study is planned as a prospective, multicenter,  randomized, double-blind, sham-
controlled pilot study, designed to assess the safety and efficacy of the Vibrant capsules 
with two new vibrating modes.  
After a run-in period of 14-21 days, subjects will be randomized with a ratio of 1:1:1 to 
either active capsule with vibrating mode 1, or 2 , or sham capsule. The subjects will then 
be treated with the active Vibrant or sham capsule for 8 weeks. The first 2 weeks of 
treatment will be considered as a subjects’ training period. 
17.2 
Study Endpoints 
17.2.1 
Primary Efficacy Endpoint 
The primary efficacy endpoints are:  
• the CSBM1 success rate, defined as 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. 
• the CSBM2 success rate, defined as 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. 
 
17.2.2 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints include:  
- 
Change from baseline in average straining 
- 
Change from baseline in average stool consistency, using the Bristol Stool Scale 
- 
Change from baseline in average bloating. 
- 
SBM success rate, defined as an increase from run-in perdion at least one weekly 
spontanuous Bowel Movement (SBM) during at lease 6 out of 8 weeks of 
treatment  
 
Additional efficacy end points 
- 
 Change from baseline in weekly number of Spontaneous Bowel Movement 
(SBM). 
- 
Change from baseline in weekly number of Complete Spontaneous Bowel 
Movement (CSBM). 
- 
Change from baseline in average abdominal gas. 
- 
Change from baseline in average abdominal pain. 
- 
Change from baseline in abdominal discomfort. 

 
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- 
Time to occurrence of spontaneous bowel movement after first capsule activation. 
- 
Treatment satisfaction score using the TSQM (Treatment Satisfaction 
Questionnaire for Medication) 
- 
Ease of use of the device. 
 
Safety Endpoints 
Safety endpoints include all adverse events related and unrelated to the study treatment. 
 
17.3 
Sample size 
No sample size assessment was performed.  
A sample size of 15 subjects in each study arm is deemed sufficient to achieve the trial 
goals.  
The sample size will be increased to at least 66 subjects (22 in each arm) to account for a 
potential 10% of drop-outs. 
17.4 
Randomization 
 
After a subject meets the eligibility criteria, he/she will be equally allocated (with a 1:1:1 
ratio) to one of the following four treatment groups based on a randomization scheme 
with fixed blocks stratified by center:  
• 
Active capsule with vibrating mode 1 administered 2 times per week 
• 
Active capsule with vibrating mode 2 administered 2 times per week 
• 
 
• 
Sham capsule administered 2 times per week 
The randomization scheme will be prepared by BioStats using the SAS® (version 9.4.) 
random number generating procedure. 
17.5 
Blinding 
This is a double blind study, the subjects, the investigators and the evaluators will be 
blinded to the treatment allocated to each subject. 
17.6 
Data Analysis Sets 
17.8.1 
Intent to Treat (ITT) 
The ITT analysis set will consist of all subjects randomized. In accordance with the ITT 
principle, all subjects randomized will be kept in their originally assigned treatment 
group. Subjects with no valid post baseline assessment will not be part of the relevant 
analyses. 
17.8.2 
Modified Intent to Treat (mITT) 
The mITT analysis set will consist of all randomized subjects who met the inclusion 
criteria of the protocol and successfully completed Visit 1. In accordance with the ITT 

 
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principle, all subjects randomized will be kept in their originally assigned treatment 
group. Subjects with no valid post baseline assessment will not be part of the relevant 
analysis. 
17.8.3 
Per-Protocol (PP) 
The per-protocol analysis set will consist of all subjects from the mITT analysis set 
without major protocol violations and successfully completed the study. 
17.8.4 
Statistical Analysis of Analysis Sets 
The ITT analysis set will serve as the main set for safety assessments . 
The efficacy assessment will be presented on the ITT, mITT and PP analysis sets. 
17.9 
Statistical Analysis 
17.9.1 
General Considerations 
Statistical analyses will be performed using SAS® v9.4 or higher (SAS Institute, Cary 
NC, USA). 
Baseline demographic and other baseline characteristics, together with safety analyses 
will be performed on all enrolled subjects. Baseline values are defined as the last valid 
value prior to treatment. 
The efficacy endpoints are mainly descriptive in nature. 
Nevertheless, if statistical tests will be performed, they will be two-sided and nominal p-
values will be presented. Where confidence limits are appropriate, non-adjusted two-
sided 95% confidence interval will be constructed . 
For comparison of means (continuous variables), the two-sample t-test or the Wilcoxon 
rank sum test will be used as appropriate.  For comparison of proportions (categorical 
variables), the Chi-squared test or Fisher’s exact test will be used as appropriate . 
17.9.2 
Significance levels and handling of type I 
error 
17.9.2.1 Type I Error 
The significance level for this study is 5% using two-tailed tests. The endpoints are 
mainly descriptive in nature, no adjustment for multiple testing will be performed.  
  
17.9.3 
Demographic and Other Baseline Variables 
Demographic and baseline condition related characteristics will be tabulated. Continuous 
variables will be summarized by a mean, standard deviation, minimum, median and 
maximum, and categorical variables by a count and percentage . 

 
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17.9.4 
Disposition of Subjects 
Treatment tolerability will be presented by treatment groups, the number and percent of 
subjects who fail to complete the study and the number and percent of subjects who fail 
to complete the study because of Adverse Events will be presented. Time to withdrawal 
will also be assessed and presented by Kaplan-Meier curves and will be compared using 
the Log-Rank test if relevant. 
17.9.5 
Efficacy Analysis 
The subject’s CSBM1 success status (i.e. if the subjects achieve an increase from 
baseline of at least 1 weekly CSBM during at least 6 out of the 8 treatment weeks) will be 
modeled by study arm with a logistic regression model, with the baseline weekly number 
of CSBM and site as covariates. The adjusted success rate per study arm, and their 
difference between the groups will be presented along with their respective 95% 
Confidence Intervals (CI).  
 
The CSBM2 success rate will be analyzed in the same manner. 
 
Subset additional analysis: The primary analysis (of both primary endpoints) will be 
repeated on the subset of subjects who were compliant (at least 70% compliance with 
capsule activation and diary) during the first 2 weeks of the treatment. 
 
The SBM success rate will be analyzed in the same manner. 
 
The change from baseline in number of weekly CSBM will be modeled with an Analysis 
of Covariance (ANCOVA) model, with baseline weekly number of CSBM and site as 
covariates. The adjusted means of the change from baseline per study arm, and their 
difference between the groups will be presented along with their respective 95% CI. 
 
The change from baseline in count of weekly SBM, and in symptoms will be analyzed 
with similar ANCOVA models, with their respective baseline values as covariate. 
 
Time to occurrence of SBM after intake of the first Vibrant capsule (either active or 
sham) will be assessed and presented by Kaplan-Meier curves and will be compared 
between the study arms using the Log-Rank test if relevant. 
 
Treatment satisfaction, and ease of use will be presented in tabular form. 
 
17.9.6 
Treatment by Center Interaction 
It is expected that only a few subjects will receive each study treatment per site, therefore 
it will not be possible to assess the treatment by center interaction.. 
 

 
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17.9.7 
Safety Analysis 
Adverse events (AE) will be presented by seriousness, severity and relation to treatment 
by treatment group. The number of reports, the number of subjects, and the incidence 
(percent of subjects) will be tabulated by study arm. 
17.9.8 
Handling of Missing Data 
 
Subjects with less than 6 weeks of diary data will be considered as failures for the 
CSBM1, the CSBM2 and SBM success rates. 
 
Multiple imputation for binary data will be used as the primary imputation method in the 
case of missing data for the primary performance end-points. 
In addition, a sensitivity analysis might be performed, where subjects with less than 2 
weeks (with at least 5 days each week) of valid diary data will be considered as non-
evaluable and omitted from the analyses. 
Additional sensitivity analysis of the primary end-point will be performed to assess the 
impact of missing data on the study outcome using possible imputation methods for 
binary data:  
• Observed Data: Use only subjects with 8 weeks of non-missing diary data and 
who did not withdraw early from study  
• Dropout/AE Imputation: A subject with no post baseline measurement of CSBM 
or a subject withdrawn due to an adverse event or treatment intolerability should 
be considered as a non-responder for this analysis. 
• Best Case Scenario: Assume all subjects with missing data in study group are 
successes; Assume all subjects in the sham group with missing data are failures. 
• Worst Case Scenario: Assume all subjects with missing data in study group are 
failures; Assume all subjects in the sham group with missing data are successes. 
 
For the time to first SBM analysis, subjects with no known SBM will be considered left 
censored. 
For the analyses of the other endpoints, no imputations for missing values will be 
performed. 
17.9.9 
Interim Analysis. 
No interim analysis is planned for this study. 
 
18. 
DATA MONITORING PLAN  
 
The Principal Investigator and his study staff will monitor all data accrual. In addition a 
data monitor will visit the study site during the study and review the progress of the 
clinical trial including safety data and ensure as possible that it is conducted, recorded, 

 
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and reported in accordance with the protocol, Good Clinical Practice (GCP), and the 
applicable regulatory requirement(s). A written report form will be issued after each 
monitoring visit (including initiation and close out visits). The monitoring visit report 
will include a summary of what the monitor reviewed and the monitor's statements 
concerning the significant findings/facts, deviations and deficiencies, conclusions, actions 
taken or to be taken and/or actions recommended to secure compliance. The 
investigator/institution should provide direct access to source data/documents for trial-
related monitoring and auditing, IRB/IEC review and inspection by the appropriate 
regulatory authority/ies.  
 
Verification during monitoring visit will include: 
 
1. That the investigator has adequate qualifications and resources and remains adequate 
throughout the trial period, that facility, including laboratories, equipment, and staff, 
are adequate to safely and properly conduct the trial and remain adequate throughout 
the trial period. 
2. Verifying for the investigational product(s): 
a. That storage conditions are acceptable. 
b. That the investigational product(s) are supplied only to subjects who are 
eligible to receive it according to protocol and no other use is being done 
with the Vibrant devices. 
c. That the receipt, use, and return of the investigational product(s) at site are 
controlled and documented adequately and that supplies delivery notes are 
confirmed upon reception throughout the trial. 
d. That the unused investigational product(s) at sites will be returned. 
3. Verifying that the investigator follows the approved protocol and all approved 
amendment(s), if any. 
4. Verifying that written informed consent was obtained before each subject's 
participation in the trial. 
5. Ensuring that the investigator receives the current Investigator's Brochure, all 
documents, and all trial supplies needed to conduct the trial properly and to comply 
with the applicable regulatory requirement(s). 
6. Ensuring that the investigator and the investigator's trial staff are adequately informed 
about the trial. 
7. Verifying that the investigator and the investigator's trial staff are performing the 
specified trial functions, in accordance with the protocol and any other written 
agreements, and have not delegated these functions to unauthorized individuals. 
8. Verifying that the investigator is enrolling only eligible subjects and at sufficient 
recruitment rate. 
9. Verifying that source documents and other trial records are accurate, complete, kept 
up-to-date and maintained. 
10. Verifying that the investigator provides all the required reports, notifications, 
applications, and submissions, and that these documents are accurate, complete, 
timely, legible, dated, and identify the trial. 

 
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11. Checking the accuracy and completeness of the CRF entries, source documents and 
other trial-related records against each other.  
12. The data required by the protocol are reported accurately on the CRFs and are 
consistent with the source documents. 
13. Adverse events, concomitant medications and intercurrent illnesses are reported in 
accordance with the protocol on the CRFs. 
14. Visits that the subjects fail to make, tests that are not conducted, and examinations 
that are not performed are clearly reported as such on the CRFs. 
15. All withdrawals and dropouts of enrolled subjects from the trial are reported and 
explained on the CRFs. 
16. Verifying that the investigator had answered all of the queries that came up from 
inspection of the CRFs or other trial material. 
17. That the investigator is maintaining the essential documents.  
18. Verifying that deviations from the protocol, SOPs, GCP, and the applicable 
regulatory requirements are reported by the investigator to the IRB/IEC and that 
appropriate actions were taken to prevent recurrence of the detected deviations. 
 
Should there be an unexpected number of device failures or related complications that 
increase the risks to the participants, or critical efficacy endpoints at intervals that are not 
satisfying, the study will be halted and analysis performed to determine whether to 
continue, modify the protocol, or close the study. 
 
19. 
DATA CONFIDENTIALITY  
 
Each subject will be identified by his/ her initials and a unique subject identification 
number. Source data will be stored with source documents. The Investigator Site Files 
(ISF) will be held in a secure area. The subject’s name and personal data will remain 
confidential and will not be published in any way. However, the sponsor’s monitor or 
representative and regulatory representatives, auditors and inspectors may have access to 
medical files in order to verify authenticity of data collected. 
 
20. 
FUNDING  
 
The study is funded by Vibrant Ltd.  
21. 
ETHICS  
 
Prior to study initiation the site shall obtain EC or IRB approval of the study. A copy of 
the written EC approval must be provided to the sponsor prior to the start of the study. 
Any changes in the study protocol, informed consent forms, or investigator must be re-
approved by the EC or IRB and the approval documented. All subjects enrolled in the 
study will provide their consent prior to entering the study. An informed consent form 

 
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shall be signed and dated by the subject. The investigator will retain the forms as part of 
the study records.  
This study will be executed in accordance with the Declaration of Helsinki, in agreement 
with the guidelines for conducting a clinical investigation in accordance with the 
principles of ICH GCP outlined in the E6 document. By signing the present protocol, the 
investigator commits to carry it out in accordance with local legal requirements. 
 
Other investigator responsibilities relative to the EC include the following: 
1. During the conduct of the study, the investigator will submit progress reports to the 
EC as required, and request re-review and approval of the study at least once a year; 
2. The investigator will report immediately to the EC of any unexpected serious adverse 
events that occur during the study, and provide the sponsor with a copy of the 
correspondence; 
3. If the sponsor notifies about serious adverse events reported in other studies using this 
device, the investigator must report that information to the EC; 
4. As required, the investigator must obtain approval from the EC for protocol 
amendments and for revisions to the consent form or subject recruitment 
advertisements; 
5. The investigator should provide the EC with any other information it requests before 
or during conduct the study; 
6. The investigator must maintain a file of study-related information that includes all 
correspondence with the EC; 
7. The investigator must notify EC when study is completed (i.e. after the last study visit 
of the final study subject); 
8. After study completion (within 12 months is recommended) the investigator should 
provide the EC with a final report on the study. The recommended components of a 
final report are as follows; dates of study start and completion, number of subjects 
enrolled/treated, number of subjects who discontinued participation early and reason 
why, itemization and discussion of any serious adverse event. 
  
22. 
INFORMED CONSENT  
 
Written informed consent must be obtained from each study subject. The subject will be 
asked to read the informed consent form and to sign the form to indicate consent to 
participate in the study.  
The investigator will explain carefully to the subject the research nature of the study. The 
scope and aims of the research will be described together with known or foreseeable 
benefits, risks and discomforts that subjects may experience. Appropriate alternative 
treatments will be discussed so that the subject may determine whether or not he or she 
wishes to participate in the study.  The subject must understand that throughout the study 
his or her participation remains voluntary and protected by the Declaration of Helsinki.  
The investigator is responsible for obtaining written (or witnessed) informed consent 
from potential subjects prior to study entry.  Subjects will be given time to read the 
informed consent and ask any questions before being asked to sign the form.  The 

 
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informed consent (approved by the sponsor and the Ethics Committee) must be signed 
and dated by the subject and the investigator. One copy of the signed consent will be 
given to the subject, a second copy will be sent to the referral investigator and the 
original will be retained by the investigator.  
Subjects may withdraw their consent to participate in the study at any time without 
prejudice. The investigator may withdraw a subject if, in his clinical judgment, it is in the 
best interest of the subject or if the subject cannot comply with the protocol. Attempts 
should be made to complete any examinations and the sponsor must be notified of all 
withdrawals.  
Should a protocol amendment be made, the subject's consent form may be revised to 
reflect the changes of the protocol. It is the responsibility of the investigator to ensure that 
an amended informed consent is approved or reviewed by the EC, and that it is signed by 
all subjects subsequently entered in the study and those currently in the study, if affected 
by the amendment. 
 
23. 
REGULATORY AND HEALTH AUTHORITY AUDITS 
The European Union’s authorities and/or the Food and Drug Administration (FDA) 
and/or the local state health authorities may request access to all study records, including 
source documents for inspection. The investigator and hospital staff are requested to 
cooperate with these audits. The investigator must notify the sponsor of any health 
authority audit as soon as notification of such audit is made. A representative or designee 
of the sponsor may also conduct similar audits and may be present during health authority 
audit. 
 
24. 
ELECTRONIC REPORTING OF DATA 
 
All medical data in this trial are to be recorded directly in the EDC (Electronic Data 
Capture) system. Documentation on paper will be restricted to exceptional circumstances 
only. 
The investigator must ensure the accuracy, completeness and timeliness (and legibility in 
case of documentation on paper) of data. 
 
Sites will get trained on how to access and use the EDC and will be foreseen with a 
personal user login and password.  
Subjects will access and complete their diaries online via a website specifically created 
for the purposes of the study. Subjects will be trained on how to access and use this 
website and will be foreseen with a personal user login and password. 
 
 

 
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25. 
RECORD RETENTION 
It is required that a copy of all records (e.g., informed consent documents, source 
documents, safety reports, study device dispensing record, etc.) which support case report 
forms for this study, be retained in the files of the responsible investigator for a minimum 
of fifteen (15) years following notification by the sponsor that all investigations (not 
merely the investigator's portion) are completed, terminated and/or discontinued.  If the 
principal investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who 
will accept the responsibility. Vibrant Ltd. must be notified in writing of the name and 
address of the new custodian. 
26. 
PROTOCOL MODIFICATIONS 
An amendment to the protocol may be proposed by an investigator. The amendment will 
be prepared and approved by the sponsor according to the sponsor’s relevant SOP. The 
amendment must be submitted to the IRB. When applicable, the amendment’s 
implementation will take place only once approved by the IRB. 
If for any unexpected reasons, there is any requirement to deviate from the treatments 
stated above, the protocol deviation should be discussed with a Vibrant Ltd. 
representative.  
 
27. 
PUBLICATION POLICY 
All information concerning this study that was not previously published is considered 
confidential information. This confidential information shall remain the sole property of 
Vibrant Ltd.; it shall not be disclosed to others without written consent of Vibrant Ltd. 
and shall not be used except in the performance of this study. 
Any investigator involved with this study is obligated to provide the Sponsor with 
complete test results and all data derived from the study. 
 
28. 
SUBJECT / STUDY DISCONTINUATION 
 
Subjects should be removed from the study whenever considered necessary for their 
welfare or when the subject expresses a desire to withdraw from the study. Non-
compliance with the protocol, the occurrence of a Serious Adverse Event or any medical 
condition that, in the opinion of the investigator, warrants discontinuation from the study 
for the safety of the subject, may necessitate discontinuing a subject. If a subject is 
discontinued, the reason must be entered on the case report form and signed by the 
investigator. In case of any questionable situation, the study monitor or Vibrant Ltd. 
personnel should be consulted. When a subject is removed from the study as a result of 
Serious Adverse Event, a final physical examination must be performed. Subjects 
removed from the study because of an adverse event will be followed-up until the adverse 
event has been resolved. 

 
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In the case that the occurrence of adverse events is greater than anticipated, the clinical 
investigation will be suspended; in such a case, a safety committee will be arranged to 
decide if the study could be continued. The Ethics Committee will be notified and the 
results of the safety committee discussions will be brought for the EC review and 
decision. 
 
Early termination could be a result of: 
1. Withdrawal of informed consent by the subject. 
2. Subjects who after inclusion develop medical diseases which may affect the 
function and interpretation of study results. 
3. Serious protocol deviation. 
4. Non-compliance with medical device administration or study procedures as 
determined by the sponsor. 
5. Change in subject's condition. 
6. Subject is Lost to follow-up. 
7. Confirmed pregnancy. 
8. Regulatory authorities stop the trial. 
 
During the study, subjects exiting the trial will be replaced with new subjects, in order to 
have approximately 66 subjects at the end of the trial. 
 
Vibrant Ltd., reserves the right to discontinue any study for administrative reasons at any 
time, such as, but not limited to a decision to discontinue further clinical investigation 
with the device, improper conduct of the study by the investigator, inability to obtain the 
number of subjects required by the protocol, etc.  Reimbursements for reasonable 
expenses will be made if such an action is necessary. 
 
29. 
DEVICE ACCOUNTABILITY  
 
Complete traceability records will be kept of all devices during the study. Vibrant devices 
and relevant accessories will be provided by Vibrant Ltd., bearing required labeling. 
Device identification and accessory identification will be documented in subject medical 
records, CRF and in center log. 
 
Each clinical investigator will be responsible for the safe storage with restricted access of 
the investigational materials in their possession, thereby preventing use of any materials 
by any persons not participating in the study. 
All base units and remaining capsules (untouched or taken out of the blister package) 
must be brought back by the subjects to the site by the time they exit the study. The 
number of remaining capsules must match the information transmitted by the base unit 
about capsule activations and the information gathered about the subject’s treatment 
compliance throughout the study. In order to perform this task, the Sponsor, CRO and 
study coordinator will rely on the same platform used to monitor protocol deviations 

 
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related to treatment compliance.  A final account, and the whereabouts of each capsule 
provided to the subject will be documented in the EDC by the study coordinator. Capsule 
failures will not be documented in the EDC but on the external platform, using the base 
unit information. 
 
After completion of the study, all unused or remaining devices must be returned in their 
original package to Vibrant Ltd. Hakochav, Yokneam 2069206 P.O.Box 516, Israel. 
All investigators will be responsible for using the products according to the IFU and 
protocol and maintaining product inventory and records. 
 
30. 
APPENDICES 
A. Appendix A – Bristol Stool Scale 
B. Appendix B – Full list of Adverse Events – Phase 3 clinical investigation 
C. Appendix C - Rome III questionnaire and instructions for completion 
D. Appendix D – TSQM questionnaire 
E. Appendix E – Ease of use questionnaire 
F. Appendix F - Subject daily diary 
 
31. 
REFERENCES  
 
1. American College of Gastroenterology Chronic Constipation Task Force. An 
evidence-based approach to the management of chronic constipation in North 
America. Am J Gastroenterol. 2005;100 Suppl 1:S1–4. 
2. Wilson N, Schey R. Lubiprostone in constipation: clinical evidence and place in 
therapy. Ther Adv Chronic Dis. 2015 Mar;6(2):40–50. 
3. Johanson JF, Kralstein J. Chronic constipation: a survey of the subject 
perspective. Aliment Pharmacol Ther. 2007 Mar 1;25(5):599–608. 
4. Rome III Diagnostic Criteria [Internet]. [Accessed 2015 Nov 3]. Available from: 
http://www.romecriteria.org/criteria/ 
5. Only 27% of European subjects with chronic constipation are satisfied with 
current treatment options [Internet]. [Accessed 2015 Nov 3]. Available from: 
https://www.ueg.eu/education/document-
detail/?name=only_27_of_european_subjects_with_chronic_constipation_are_sati
sfied_with_current_treatment_options&file=89240 
6. Ford AC, Moayyedi P, Lacy BE, Lembo AJ, Saito YA, Schiller LR, et al. 
American College of Gastroenterology monograph on the management of irritable 
bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014 
Aug;109 Suppl 1:S2–26; quiz S27. 

 
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7. Paré P, Fedorak RN. Systematic review of stimulant and nonstimulant laxatives 
for the treatment of functional constipation. Can J Gastroenterol Hepatol. 2014 
Nov;28(10):549–57. 
8. Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, et al. Two 
randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 
11;365(6):527–36. 
9. Soubra M, Schey R. Lubiprostone for the treatment of adult women with irritable 
bowel syndrome with constipation. Clin Med Insights Gastroenterol. 2012;5:23–
30.  
10. Wald A. Severe constipation. Clin Gastroenterol Hepatol 2005; 3: 432–5. 
11. Cheung O, Wald A. Management of pelvic floor disorders. Aliment Pharmacol 
Ther 2004; 19: 481–95. 
12. Tack J, Müller-Lissner S, Stanghellini V, Boeckxstaens G, Kamm MA, Simren 
M, et al. Diagnosis and treatment of chronic constipation--a European 
perspective. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2011 
Aug;23(8):697–710.  
13. Do Stool Form and Frequency Correlate With Whole-Gut and Colonic Transit 
?  Results From a Multicenter Study in Constipated Individuals and Healthy 
Controls [Accessed March 30th, 2016 
https://www.researchgate.net/publication/38066000_Do_Stool_Form_and_Freque
ncy_Correlate_With_Whole-
Gut_and_Colonic_Transit_Results_From_a_Multicenter_Study_in_Constipated_I
ndividuals_and_Healthy_Controls] 
14. T2081 Bristol Stool Form in Slow Transit Constipation Correlates Inversely With 
Regional Colon Contractile Activity Measured by a Wireless Motility Capsule 
[Accessed March 30th, 2016 http://www.gastrojournal.org/article/S0016-
5085%2810%2962894-6/pdf] 
15. Stool form scale as a useful guide to intestinal transit time. [Accessed March 30th, 
2016 http://www.ncbi.nlm.nih.gov/pubmed/9299672] 
16. Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment 
satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), 
using a national panel study of chronic disease. Health Qual Life Outcomes. 
2004;2:12. Those seeking information regarding or permission to use the TSQM 
are 
directed 
to 
Quintiles 
at 
www.quintilesims.com/TSQM 
or 
TSQM@quintilesims.com 
 
 

 
VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 68 of 85 
 
 
 
 
 

 
VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 69 of 85 
 
 
 
APPENDIX A – Bristol Stool Scale 
 
 
The Bristol Stool Scale:  
 
How to analyze stools: 
 
Type 1: Stools appear in separate, hard lumps, similar to nuts. Type 
1 stools remained in the colon the longest amount of time; a sure 
sign you’re constipated; most common stools. 
 
Type 2: Stools are sausage-like in appearance but lumpy. Indicate 
toxic constipation and need for intestinal cleansing 
 
Type 3 (Normal): Stools come out similar to a sausage but with 
cracks in the surface. 
 
Type 4 (Normal): Stools are smooth and soft in the form of a 
sausage or snake. 
 
Type 5: Stools form soft blobs with clear-cut edges, and easily pass 
through the digestive system. Soft diarrhea, it may indicate a 
possible risk for bowel disease; also indicate you are toxic and need 
regular intestinal cleansing. 
 
Type 6: Stools have fluffy pieces with ragged edges. Considered 
mushy stools, they indicate diarrhea; and that you are toxic and 
need regular intestinal cleansing. 
 
Type 7: Stool is mostly liquid with no solid pieces. Passed quickly 
through the colon; is indicative of severe diarrhea possibly as a 
result of a viral or bacterial infection. See a doctor as soon as 
possible. 
 
 
 

 
VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 70 of 85 
 
 
 
Appendix B - Full list of Adverse Events – Phase 3 clinical investigation 
 
 
Vibrant 
Sham 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Fisher's 
exact test 
p-value 
All 
252 
51 
62.20% 
183 
44 
54.32% 
0.3426 
Abdominal cramping 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Abdominal pain/cramping/discomfort 
27 
14 
17.07% 
21 
14 
17.28% 
1.0000 
Aggravation of constipation 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Allergy 
2 
2 
2.44% 
. 
. 
. 
0.4969 
Anxiety attack 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Arthritis (viral) 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Asthma flare 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Back pain and/or back spasm 
5 
5 
6.10% 
7 
2 
2.47% 
0.4429 
Benign viral infection / syndrome 
. 
. 
. 
2 
2 
2.47% 
0.2454 
Bloating and/or Flatulence 
31 
16 
19.51% 
52 
22 
27.16% 
0.2710 
Blood in stool 
1 
1 
1.22% 
2 
2 
2.47% 
0.6204 
Blood test abnormal 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Bruising on arms and/or legs 
2 
1 
1.22% 
. 
. 
. 
1.0000 
Bruising on the flank 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Chest pain 
. 
. 
. 
2 
1 
1.23% 
0.4969 
Common cold / head cold 
3 
3 
3.66% 
6 
6 
7.41% 
0.3283 
Congestion 
2 
2 
2.44% 
2 
1 
1.23% 
1.0000 
Cough 
1 
1 
1.22% 
1 
1 
1.23% 
1.0000 
Cystitis 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Dental infection (due to extraction of 
wisdom tooth) 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Diaphragm pain 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Diarrhea 
15 
8 
9.76% 
3 
3 
3.70% 
0.2105 
Discomfort 
. 
. 
. 
2 
2 
2.47% 
0.2454 
Discomfort - indigestion 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Discomfort - stomach 
1 
1 
1.22% 
1 
1 
1.23% 
1.0000 
Dizziness 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Emesis 
3 
3 
3.66% 
2 
2 
2.47% 
1.0000 
Emesis - induced by GERD 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Fatigue 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Fever 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Flu 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Fracture of the nose 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Gagging on capsule 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Galactorrhea 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Gastroenteritis 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Headache 
38 
13 
15.85% 
17 
11 
13.58% 
0.8256 
Heartburn 
2 
2 
2.44% 
2 
2 
2.47% 
1.0000 
Hemorrhoids 
2 
2 
2.44% 
. 
. 
. 
0.4969 
Herpes 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Hypercholesterolemia 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Hyperkalemia 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Hypertension 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Infection of a furuncle 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Infection of the upper respiratory tract 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Inflammation of salivary gland 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Insomnia 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Migraine 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Nausea 
18 
9 
10.98% 
8 
6 
7.41% 
0.5894 

 
VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 71 of 85 
 
 
 
 
Vibrant 
Sham 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Number of 
Reports 
Number of 
Subjects 
Incidence 
Fisher's 
exact test 
p-value 
Pain in belly button 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Pain in hip 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pain in leg 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pain in muscle (neck) 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Pain in muscle (right trapezius) 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pain in the back and legs 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Pain in the chest 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pain in the hand 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pain in tooth 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Pneumonia 
2 
2 
2.44% 
. 
. 
. 
0.4969 
Rectal bleeding 
3 
2 
2.44% 
. 
. 
. 
0.4969 
Rectal cramping / spasm 
12 
2 
2.44% 
. 
. 
. 
0.4969 
Sensation of burning - abdomen (right 
lower quadrant) 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Sensation of vibration in abdomen 
50 
14 
17.07% 
2 
2 
2.47% 
0.0027 
Sinusitis 
2 
2 
2.44% 
1 
1 
1.23% 
1.0000 
Skin rash - both hands 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Stomach ache and/or cramp 
7 
5 
6.10% 
20 
6 
7.41% 
0.7657 
Surgery - Eyes (laser) 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Surgery - trauma of the toe 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Surgery - wisdom tooth extraction 
. 
. 
. 
1 
1 
1.23% 
0.4969 
TSH level - low 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Throat ache 
. 
. 
. 
2 
2 
2.47% 
0.2454 
Trauma - knee 
. 
. 
. 
1 
1 
1.23% 
0.4969 
Trauma - right hip 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Urinary Tract Infection 
1 
1 
1.22% 
2 
2 
2.47% 
0.6204 
Vitreous collapse 
1 
1 
1.22% 
. 
. 
. 
1.0000 
Weight gain 
1 
1 
1.22% 
. 
. 
. 
1.0000 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 72 of 85 
 
 
 
APPENDIX C – ROME III (Questionnaire and Instructions for Completion) 
 
Instructions for completion: 
Complete questions 41 to 67 only. 
 
Scoring Algorithm:  
 
Irritable Bowel Syndrome 
Diagnostic Criteria* 
Recurrent abdominal pain or discomfort at least 3 days/month in last 3 months associated with 
two or more of criteria #1– #3 below: 
Pain or discomfort at least 2–3 days/month (question 41 > 2) 
For women, does pain occur only during menstrual bleeding? (question 43=0 or 2) 
1. Improvement with defecation 
Pain or discomfort gets better after BM at least sometimes (question 46 > 0) 
2. Onset associated with a change in frequency of stool 
Onset of pain or discomfort associated with more stools at least sometimes (question 47 > 0), 
OR 
Onset of pain or discomfort associated with fewer stools at least sometimes (question 48 > 0) 
3. Onset associated with a change in form (appearance) of stool 
Onset of pain or discomfort associated with looser stools at least sometimes (question 49 > 
0), OR 
Onset of pain or discomfort associated with harder stools at least sometimes (question 50 > 
0) 
 
* Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis 
Yes. (question 45=1) 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 73 of 85 
 
 
 
Functional Constipation 
Diagnostic criteria* 
1. Must include two or more of the following: 
a. Straining during at least 25% of defecations. At least often. (question 54 > 1) 
b. Lumpy or hard stools at least 25% of defecations. At least often. (question 53 > 1) 
c. Sensation of incomplete evacuation at least 25% of defecations. At least sometimes. (question 
55 > 0) 
d. Sensation of anorectal obstruction/blockage at least 25% of defecations. At least sometimes. 
(question 56 > 0) 
e. Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support 
of the pelvic floor). At least sometimes. (question 57 > 0) 
f. Fewer than three defecations per week. At least often. (question 52 > 1) 
 
2. Loose stools are rarely present without the use of laxatives. 
Loose stools occur never or rarely (question 49=0), & 
3. Insufficient criteria for IBS 
Diagnostic criteria for IBS not met 
 
* Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. 
Yes. (question 59=1) 
 
 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 74 of 85 
 
 
 
 
 
 
 
APPENDIX D – TSQM Questionnaire 
 
TSQM (Version 1.4) 
Treatment Satisfaction Questionnaire for Medication 
 
Instructions:  Please take some time to think about your level of satisfaction or 
dissatisfaction with the treatment you are taking in this clinical trial.  We are 
interested in your evaluation of the effectiveness, side effects, and convenience of 
the treatment over the last two to three weeks, or since you last used it.  For each 
question, please place a single check mark next to the response that most closely 
corresponds to your own experiences. 
 
1. How satisfied or dissatisfied are you with the ability of the treatment to prevent or treat your 
condition?  
 □1   Extremely Dissatisfied 
□2   Very Dissatisfied 
□3   Dissatisfied 
□4   Somewhat Satisfied 
□5   Satisfied 
□6   Very Satisfied 
□7   Extremely Satisfied 
 
2. How satisfied or dissatisfied are you with the way the treatment relieves your symptoms?  
 □1   Extremely Dissatisfied 
□2   Very Dissatisfied 
□3   Dissatisfied 
□4   Somewhat Satisfied 
□5   Satisfied 
□6   Very Satisfied 
□7   Extremely Satisfied 
 
3. How satisfied or dissatisfied are you with the amount of time it takes the treatment to start 
working?  
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 75 of 85 
 
 
 
□1   Extremely Dissatisfied 
□2   Very Dissatisfied 
□3   Dissatisfied 
□4   Somewhat Satisfied 
□5   Satisfied 
□6   Very Satisfied 
□7   Extremely Satisfied 
 
 
 
4.  As a result of taking this treatment, do you experience any side effects at all? 
 □1   Yes 
□0   No  (if No, then please skip to Question 9) 
  
5. How bothersome are the side effects of the treatment you take to treat your condition?  
 □1   Extremely Bothersome 
□2   Very Bothersome 
□3   Somewhat Bothersome 
□4   A Little Bothersome 
□5   Not at All Bothersome 
 
6. To what extent do the side effects interfere with your physical health and ability to function 
(i.e., strength, energy levels, etc.)?  
 □1   A Great Deal 
□2   Quite a Bit 
□3   Somewhat 
□4   Minimally 
□5   Not at All 
 
7. To what extent do the side effects interfere with your mental function (i.e., ability to think 
clearly, stay awake, etc.)?  
 □1   A Great Deal 
□2   Quite a Bit 
□3   Somewhat 
□4   Minimally 
□5   Not at All 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 76 of 85 
 
 
 
8. To what degree have treatment side effects affected your overall satisfaction with the 
treatment?  
 □1   A Great Deal 
□2   Quite a Bit 
□3   Somewhat 
□4   Minimally 
□5   Not at All 
 
9. How easy or difficult is it to use the treatment in its current form?  
 □1   Extremely Difficult 
□2   Very Difficult 
□3   Difficult 
□4   Somewhat Easy 
□5   Easy 
□6   Very Easy 
□7   Extremely Easy 
 
10. How easy or difficult is it to plan when you will use the treatment each time?  
 □1   Extremely Difficult 
□2   Very Difficult 
□3   Difficult 
□4   Somewhat Easy 
□5   Easy 
□6   Very Easy 
□7   Extremely Easy 
 
11. How convenient or inconvenient is it to take the treatment as instructed?  
 □1   Extremely Inconvenient 
□2   Very Inconvenient 
□3   Inconvenient 
□4   Somewhat Convenient 
□5   Convenient 
□6   Very Convenient 
□7   Extremely Convenient 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 77 of 85 
 
 
 
12. Overall, how confident are you that taking this treatment is a good thing for you?  
 □1   Not at All Confident 
□2   A Little Confident 
□3   Somewhat Confident 
□4   Very Confident 
□5   Extremely Confident 
 
13. How certain are you that the good things about your treatment outweigh the bad things?  
 □1   Not at All Certain 
□2   A Little Certain 
□3   Somewhat Certain 
□4   Very Certain 
□5   Extremely Certain 
 
14. Taking all things into account, how satisfied or dissatisfied are you with this treatment?  
 □1   Extremely Dissatisfied 
□2   Very Dissatisfied 
□3   Dissatisfied 
□4   Somewhat Satisfied 
□5   Satisfied 
□6   Very Satisfied 
□7   Extremely Satisfied 
 
 
 
Copyright Quintiles 2017. All rights reserved. 
 
 
 
 
 
 
 
 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 78 of 85 
 
 
 
 
APPENDIX E – Ease of use questionnaire 
 
Please rank the following tasks and propositions on a scale from 1 to 5 
(Circle the response that best represents your opinion) 
[1] Connecting the base unit to Wi-Fi 
1 
2 
3 
4 
5 
Very Hard 
Hard 
Medium 
Easy 
Very Easy 
[2] Setting up the base unit for use 
1 
2 
3 
4 
5 
Very Hard 
Hard 
Medium 
Easy 
Very Easy 
[3] Activating capsules 
1 
2 
3 
4 
5 
 
Very Hard 
Hard 
Medium 
Easy 
Very Easy 
[4] Knowing if the capsules have been successfully activated or not 
1 
2 
3 
4 
5 
 
Very Hard 
Hard 
Medium 
Easy 
Very Easy 
[5] Following the treatment for several months once it is commercialized (there 
would be no need to connect the base unit to Wi-Fi) 
1 
2 
3 
4 
5 
 
Very Hard 
Hard 
Medium 
Easy 
Very Easy 
[6] How likely would you be to use the capsule if it is commercially available in the 
future? 
1 
2 
3 
4 
5 
Not at all likely 
Not likely 
Neutral 
Likely 
Very likely 
 
 
 
During the study, you had a 66% chance of receiving the active treatment (vibrating capsules), 
and a 33% chance of receiving the placebo capsules (non-vibrating capsules). What type of 
capsules do you think you received? 
  Placebo Capsules (non-vibrating capsules)    
  Vibrant Capsules (vibrating capsules)        
  I don’t know / no opinion 
 
 
 
 
 
 
 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 79 of 85 
 
 
 
 
 
APPENDIX F – Subject Diaries 
 
Subject Initials: |__|-|__| 
Subject Identification Number: |__|__|-|__|__|__| 
Name of the center/site: ___________________ 
Location of the center/site: _________________ 
 
Day |__|__|of Study 
  
             Date:                          |__|__| / |__|__|__| / 20|__|__| 
 
 
                         Day              Month                 Year 
 
FORM 1: Capsules 
 
 I haven’t started treatment  
 
 I have started treatment  
If you started treatment, please specify for the day: 
 
How many capsules did you take out of the blister package?   |__| 
 
How many capsules did you swallow?  |__| 
 
Comments: 
______________________________________________________________________ 
 
______________________________________________________________________ 
What is your level of satisfaction with the treatment? 
0          1         2      3        4          5         6        7        8        9       10                                                                                       
                                                                                                                       
                                  
No satisfaction                                                               Great satisfaction 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 80 of 85 
 
 
 
 
FORM 2: Bowel movements 
 
Please note: the diary paper form allows you to enter information about up to 3 bowel 
movement for ONE day. 
 
Number of bowel movements for the day: 
 
 |__| 
If you had at least one bowel movement today, please answer, for each bowel 
movement: 
 
BOWEL MOVEMENT 1 
 
1. Time of defecation: 
|__|__|:|__|__|  am/pm 
 
2. What was consistency of the bowel movement? 
1 = Separate hard lumps, like nuts (hard to pass) 
2 = sausage-shaped, but lumpy 
3 = like a sausage but with cracks on its surface 
4 = Like a sausage or snake, smooth and soft 
5 = Soft blobs with clear-cut edges (passed easily) 
6 = fluffy pieces with ragged edges, a mushy stool 
7 = watery, no solid pieces, entirely liquid 
3. Were you left with a feeling of complete evacuation?        Yes    No 
4. How much straining was needed to have the bowel movement? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No straining                              
                                                
Unbearable straining 
 
 
5. Did you use digital maneuver in order to have the bowel movement?  Yes   No 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 81 of 85 
 
 
 
 
BOWEL MOVEMENT 2 
 
1. Time of defecation: 
|__|__|:|__|__|  am/pm 
 
2. What was consistency of the bowel movement? 
1 = Separate hard lumps, like nuts (hard to pass) 
2 = sausage-shaped, but lumpy 
3 = like a sausage but with cracks on its surface 
4 = Like a sausage or snake, smooth and soft 
5 = Soft blobs with clear-cut edges (passed easily) 
6 = fluffy pieces with ragged edges, a mushy stool 
7 = watery, no solid pieces, entirely liquid 
3. Were you left with a feeling of complete evacuation?        Yes    No 
4. How much straining was needed to have the bowel movement? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No straining                              
                                                
Unbearable straining 
 
 
5. Did you use digital maneuver in order to have the bowel movement?  Yes   No 
 
 
BOWEL MOVEMENT 3 
 
1. Time of defecation: 
|__|__|:|__|__|  am/pm 
 
2. What was consistency of the bowel movement? 
1 = Separate hard lumps, like nuts (hard to pass) 
2 = sausage-shaped, but lumpy 
3 = like a sausage but with cracks on its surface 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 82 of 85 
 
 
 
4 = Like a sausage or snake, smooth and soft 
5 = Soft blobs with clear-cut edges (passed easily) 
6 = fluffy pieces with ragged edges, a mushy stool 
7 = watery, no solid pieces, entirely liquid 
3. Were you left with a feeling of complete evacuation?        Yes    No 
4. How much straining was needed to have the bowel movement? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No straining                              
                                         
Unbearable straining 
 
 
5. Did you use digital maneuver in order to have the bowel movement?  Yes   No 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 83 of 85 
 
 
 
FORM 3: daily experience 
 
Please score your experience today, whether you had a bowel movement or not 
1. What is your level of abdominal pain for the day? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No pain                              
                                       
Unbearable pain 
 
2. What is your level of abdominal discomfort for the day? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No discomfort                              
                                         
Unbearable discomfort 
 
3. What is your level of bloating for the day? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No abdominal gas                              
                                      
Unbearable abdominal gas  
 
4. What is your level of abdominal gas for the day? 
        0  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
           
No bloating 
                                           
Unbearable bloating 
 
 
 
 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 84 of 85 
 
 
 
Has there been any change to your general health condition?        Yes    No 
If yes, please detail: 
_____________________________________________________________________________ 
_____________________________________________________________________________ 
_____________________________________________________________________________ 
_____________________________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

VIBRATING CAPSULE 
PROTOCOL FOR STUDY V-300 
Doc No: 300CLD 
Rev: 02Date: 10 January 2018 
Page 85 of 85 
 
 
 
FORM 4: rescue medication 
 
Have you taken any rescue medication?                                Yes    No 
If yes, please detail below the name and dosage 
 
 
 
FORM 5: other medication 
Have you taken any other medication/supplements?          Yes    No 
Name of drug Dosage Unit 
Time of the intake 
Number of 
takes/day 
Comments 
 
 
 
|__|__|:|__|__| am/pm    
 
 
 
 
|__|__|:|__|__| am/pm    
 
If yes, please detail below the name and reason for intake 
Name of drug 
Dosage Unit Number of 
takes/day 
Reason 
Comments