Evaluation of PillCam™ Colon 2 in Visualization of the Colon

To evaluate the performance of PillCam COLON 2 in regards to detection of patients with polyps where colonoscopy is considered as the gold standard reference.

Standard evaluation of subjects with suspected colon diseases includes endoscopic imaging by colonoscopy and radiology testing such as: air-contrast barium enema, abdominal/pelvic CT, or virtual colonoscopy. The Given® Diagnostic System offers an alternative approach for endoscopic visualization of the colon. Advantages of the Given® Diagnostic System include the elimination of the need for conscious sedation, the minimally invasive, painless nature of the exam, and the ability to pursue normal daily activities immediately following the procedure . Furthermore, compared to standard colonoscopy, the Given® Diagnostic System may be more readily accepted by the subjects, thereby improving subjects' willingness to undergo a diagnostic evaluation of the colon and comply with colorectal cancer screening recommendations. The PillCam™ SB capsule (formerly M2A® Capsule) that was cleared by the FDA- in August 2001 for small bowel evaluation has been ingested to date by more than 1,000,000 people worldwide and is well accepted by patients and physicians as well as the professional societies. However, adequate visualization of the colon cannot be achieved with the standard PillCam™ SB capsule because of the anatomical and physiological properties of the colon which are significantly different than the small bowel. Moreover, other issues that limit the evaluation of the colonic mucosa by the standard PillCam™ SB procedure include an unsatisfactory level of colon cleanliness and slow progression of the PillCam™ SB capsule through the colon during the desired examination time. Therefore, the development and introduction of a specially designed, customized colon capsule combined with a dedicated capsule colonoscopy procedure protocol will allow for more efficient evaluation of the colonic mucosa. This is expected to improve the capability of the Given® Diagnostic System to detect colonic pathologies and to serve as a diagnostic and screening tool for colonic disease. To date, several clinical studies have been conducted with Given® Diagnostic System and the PillCam™ Colon 1 capsule A pilot multicenter study is currently being conducted with a new Given® Diagnostic System and an advanced generation of the the PillCam™ Colon capsule - PillCam™ Colon 2. Capsule. The new development of Given® Diagnostic System and PillCam™ Colon 2 capsule is primarily aimed to increase sensitivity and specificity for polyp detection. Further details of the Given® Diagnostic System and PillCam™ Colon 2 capsule can be found in the device description section. This study is designed to evaluate the performance of the new version of Given® Diagnostic System and PillCam™ Colon 2 capsule in detecting patients with polyps and other colonic lesions as compared to conventional colonoscopy.

Subjects that are indicated for colonoscopy, who are suspected or known to suffer from large bowel diseases.

The accuracy parameters (i.e. sensitivity) were evaluated for detection of patients with polyps equal or larger than 6 mm and for detection of patients with polyps equal or larger than 10 mm by constructing 2X2 matrix (i.e. PCCE-2 performance versus the standard colonoscopy), where sensitivity and specificity, are presented with 95% Cl based on the binomial distribution. Standard colonoscopy is considered the gold standard.

The accuracy parameters (i.e. specificity) were evaluated for detection of patients with polyps equal or larger than 6 mm and for detection of patients with polyps equal or larger than 10 mm by constructing 2X2 matrix (i.e. PCCE-2 performance versus the standard colonoscopy), where sensitivity and specificity, are presented with 95% Cl based on the binomial distribution. Standard colonoscopy is considered the gold standard.

The diagnostic yield (%) of PCCE-2 and colonoscopy in visualizing a variety of colonic lesion excluding polyps (e.g. inflammation, diverticulosis and bleeding lesions) is provided.

Overall colon cleanliness was judged for capsule endoscopy and colonoscopy on a four-point grading index scale as follows: poor cleansing level (Large amount of fecal residue.) fair cleansing level (Enough feces or dark fluid present to preclude a completely reliable examination.) good cleansing level (Small amount of feces or dark fluid, but not enough to interfere with examination.) excellent cleansing level (No more than small bits of adherent feces.)

Capsule excretion time is defined as the duration of ingestion to capsule excretion time. The distribution of excretion times were categorized as follows: capsule excreted within 4 hours capsule excreted within 6 hours capsule excreted within 8 hours capsule excreted 8 hours and above

Inclusion criteria: Subject is between the ages of 18-70 Subject was referred to colonoscopy for at least one of the following reasons: Colorectal cancer screening for age ≥60 Clinical symptoms such as: rectal bleeding, hematochezia, melena, positive FOBT, recent change of bowel habits for age ≥50 Positive findings in the colon (e.g. Polyp ≥10mm) Personal history of significant polyps( ≥6mm )that were removed at least 3 years ago (3 years and above) Exclusion criteria Age > 70 years Subject has dysphagia or any swallowing disorder Subject has congestive heart failure Subject has known renal disease Subject is not eligible for colon preparation due to the presence of underlying conditions based on the clinical judgment of the investigator Subject has any allergy or other known contraindication to the medications used in the study Subject has had prior abdominal surgery of the gastrointestinal tract other than uncomplicated procedures that would be unlikely to lead to bowel obstruction based on the clinical judgment of the investigator Subject has a cardiac pacemaker or other implanted electro medical device. Subject is expected to undergo MRI examination within 7 days after ingestion of the capsule. Subject with any condition believed to have an increased risk for capsule retention such as Crohn's disease, intestinal tumors, radiation enteritis, incomplete colonoscopies due to obstructions or NSAID enteropathy, Subject with gastrointestinal motility disorders Subject has known delayed gastric emptying Subject has any condition, which precludes compliance with study and/or device instructions. Women who are either pregnant at the time of screening, or are of child-bearing potential and do not practice medically acceptable methods of contraception. Subject suffers from life threatening conditions Subject currently participating in another clinical study Age>70

Morgan DR, Malik PR, Romeo DP, Rex DK. Initial US evaluation of second-generation capsule colonoscopy for detecting colon polyps. BMJ Open Gastroenterol. 2016 May 3;3(1):e000089. doi: 10.1136/bmjgast-2016-000089. eCollection 2016.