confidential 1 pillcam ™ colon trial results. 2 agenda first feasibility studies – overview ...
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CONFIDENTIAL1
PillCamPillCam™™ COLON COLON
Trial ResultsTrial Results
2
AgendaAgenda
First Feasibility Studies – Overview
Study Results of MA-48 Feasibilit
3
Type # of sites PI Subjects Comparative
ArmPresenta
tion Publication
Completed
11 Feasibility 3 Eliakim, Israel 91 Colonoscopy ACG 06 Endoscopy, 10/06
22 Feasibility 1 Deviere, Belgium 41 Colonoscopy UEGW 06 Endoscopy, 10/06
33 Feasibility 1 Lewis, US 51 Colonoscopy, VC ACG 06 Work In
Progress
Work in progress
44 Pivotal 8 Deviere, Belgium 225 / 340 Colonoscopy DDW 07?
55 Pivotal 7 Rex-Eisen, US 25 / 340 Colonoscopy
To commence within few months
66 CRC screening 12 Galmiche, France 600 Colonoscopy
77 Feasibility 1 Sung, China 40 Colonoscopy
88 Feasibility 3 Riemann, Germany 50 Colonoscopy
99 Feasibility 5 PI tbd, Italy 60 Colonoscopy
10 /1110 /11 2 feasibilities 6-8 Munoz/Herrerias, Spain
60 Colonoscopy
Clinical TrialsClinical Trials
4
Conclusions from Feasibility TrialsConclusions from Feasibility Trials
“Colon Capsule Endoscopy showed promising accuracy compared with colonoscopy. This new noninvasive technique deserves further evaluation as a potential CRC screening tool.”
OctoberOctober20062006II
5
Conclusions from Feasibility TrialsConclusions from Feasibility Trials
OctoberOctober20062006
“PillCam Colon capsule endoscopy appears to be a promising new modality for colonic evaluation. Further improvements in the procedure will probably increase capsule examination completion and polyp detection rates. Additional studies are needed to evaluate the accuracy of PillCam Colon endoscopy in other populations with different prevalence levels.”
IIII
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Capsule Colonoscopy – A Pilot Three Arm, Blinded Trial of Capsule Colonoscopy, Virtual Colonoscopy and ColonoscopyBlair Lewis1, Douglas Rex2, David Lieberman3
Private practice, New York, New York1; Indiana University School of Medicine, Indianapolis, Indiana2; Oregon Health and Science University, Portland, Oregon3
Introduction: Colon capsule endoscopy (CCE) is a new endoscopic capsule for visualization of the colon. The capsule is 31x11mm. It has two imagers and obtains 4 frames per second. It is not a FDA approved device. A blinded trial was being performed to assess the feasibility and efficacy of this technology in screening patients at risk for colon polyps and cancer.
Materials and Methods: At risk volunteers were recruited. Study entry required age over 50 and not having colonoscopy within 5 years or having a family history of colon cancer or the presence of symptoms suspicious for cancer. Volunteers were paid and signed IRB approved consent forms. Patients initially underwent CCE and within 3 weeks took a second preparation and underwent virtual (VC) and standard colonoscopy (SC) on the same day. The colonoscopist was blinded to the findings of the previous tests. At SC, results of the two previous tests were serially unblinded. Results were reviewed. Significant findings were defined as any polyp ≥6mm in size or 3 or more polyps of any size.
Conclusions: Colon capsule endoscopy appears to be a promising new technology for screening the colon for polyps in patients at risk for colorectal cancer.
This feasibility study demonstrates that capsule colonoscopy appears to be a safe and promising new technology for visualizing the colon
This capsule colonoscopy may complement traditional colonoscopy for:
•Contraindicated colonoscopy
•Incomplete colonoscopy
•Patients unwilling to undergo standard colonoscopy
Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps
Inclusion Criteria: Patients between the ages of 50-75
•Indicated for CRC screening, who did not have colonoscopy in last 5 years, OR with current or recent history of IDA
Patients between the ages of 40-75•With family history of colonic polyps or CRC•With FOBT positive
Patients sign an IRB informed consent form
Exclusion Criteria: Dysphagia Known or suspected bowel obstruction High risk for capsule retention and abdominal surgery of the GI tract
within the last six months Contra-indication for any procedure prescribed in the study,
e.g., ingestion of oral sodium phosphate or polyethylene glycol solutions, Tegaserod or Bisacodyl suppository
Congestive heart failure or renal insufficiency or liver disease Cardiac pacemakers or other implanted electro medical-device Pregnancy MRI examination within 7 days after capsule ingestion Current life threatening conditions
Study Overview:• Capsule procedure:
• Day -1: Clear liquids and evening laxative as below• Day 0: Laxatives and prokinetic agents, Capsule ingestion
• Capsule video review by Investigators DR, DL*• Within 3 weeks following Capsule procedure:
• Early morning: Virtual colonoscopy by investigator JM*• Midday: Colonoscopy by investigator BL* then sequential
un-blinding * all investigators blinded to each other
Capsule Colonoscopy Preparation:Day -1 Clear Liquid diet
1800 – 2100 2 Liter PEG
Exam day 700 – 800 1 Liter PEG
815 6mg Tegaserod
830 Capsule ingestion
1040 Boost I (30ml NaP) *
1300 6mg Tegaserod
1400 Boost II (15ml NaP)
1600 Suppository 10mg Bisacodyl - if needed
1700 Regular meal
* Pending verification that the capsule had exited the the stomach using a real-time viewer .
Assessment of Bowel Cleansing:
• Poor - Large amount of fecal residue• Fair - Enough feces or dark fluid present to preclude
a completely reliable examination• Good - Small amount of feces or dark fluid, but not
enough to interfere with examination• Excellent - No more then small bits of adherent feces
Poor Fair Good Excellent
Study Results - Enrollment:• 64 patients screened - 12 failed• 52 enrolled - 1 discontinued• 51 completed trial
-Average age 54 (40-74)-28 Males, 23 Females-31 for screening-16 for family history-3 for blood in stool-1 for personal history of polyps
60%
33%
5%2%
53%
38%
7%3%
59%
35%
4%
57%
33%
11%0%
47%
27%
20%
7%
0%
20%
40%
60%
80%
100%
Ceacum Right Colon Transverse Left Colon Sigmoid-Rectum
Excellent Good Fair Poor
Results - Bowel cleanliness:
Transit Time From Ingestion to Excretion
6%
67%
84% 88% 90%100%
0
5
10
15
20
25
30
35
2:00 4:00 6:00 8:00 10:00 Later
Time [Hours]
Freq
uenc
y
0%
20%
40%
60%
80%
100%
Transit time from ingestion to Transit time from ingestion to excretionexcretion
2%
90%
6%
2%
Results - Capsule Transit:
Capsule Location at 10 hrs
Results - Polyp Detection: Polyps of any size/path were found in 29/51 patients (57%)Polyps of any size/path were found in 29/51 patients (57%)
•60 polyps by un-blinded colonoscopy60 polyps by un-blinded colonoscopy•55 polyps by colonoscopy55 polyps by colonoscopy•94 polyps by capsule colonoscopy94 polyps by capsule colonoscopy•26 polyps by virtual colonoscopy26 polyps by virtual colonoscopy
Adenomatous polyps were found in 15/51 patients (29%)Adenomatous polyps were found in 15/51 patients (29%)•17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm•16/17 detected by standard colonoscopy (1 missed and found on unblinding)16/17 detected by standard colonoscopy (1 missed and found on unblinding)•12/17 detected by capsule12/17 detected by capsule•5/17 detected by virtual colonoscopy5/17 detected by virtual colonoscopy
Results - Sensitivity and Specificity:Colonoscopy Capsule Virtual Colonoscopy
For any polyp
Sensitivity 93% (95% CI, 85-93%) 83% (95% CI, 72-92%) 38% (95% CI, 27-44%)
Specificity 100% (95% CI, 90-100%) 45% (95% CI, 31-57%) 86% (95% CI, 72-95%)
PPV 100% (95% CI, 92-100%) 67% (95% CI, 58-74%) 79% (95% CI, 56-92%)
NPV 92% (95% CI, 82-92%) 67% (95% CI, 46-83%) 51% (95% CI, 43-56%)
For significant findings *
Sensitivity 89% (95% CI, 77-89%) 56% (95% CI, 38-71%) 33% (95% CI, 20-38%
Specificity 100% (95% CI, 93-100%) 76% (95% CI, 66-84%) 97% (95% CI, 90-99%)
PPV 100% (95% CI, 86-100%) 56% (95% CI, 38-71%) 86% (95% CI, 52-97%)
NPV 94% (95% CI, 88-94%) 76% (95% CI, 66-84%) 73% (95% CI, 67-75%)
* Significant findings: Polyps ≥ 6 mm OR three or more polyps of any size
The Capsule:• 11 x 31mm• Wider angle of view• 2 Frames/second from each side• 10 gig recording device
Ø1
1 m
m
31 mm
Virtual Colonoscopy:• "Top CAT” GE 64-detector VCT was used to scan the patients' cleansed colons. • Data was compiled and reviewed in 2D and 3D on a Vitrea workstation.
Colonoscopy:• Performed under conscious sedation (Demerol/Versed)• Complete in all patients• Limited withdrawal time to less than 10 minutes to limit study effect
Polyp seen at colonoscopy Polyp seen on capsule
III Conclusions from Feasibility Trials – ACG 2006 PosterIII Conclusions from Feasibility Trials – ACG 2006 Poster
7
Capsule Colonoscopy – A Pilot Three Arm, Blinded Trial of Capsule Colonoscopy, Virtual Colonoscopy and ColonoscopyBlair Lewis1, Douglas Rex2, David Lieberman3
Private practice, New York, New York1; Indiana University School of Medicine, Indianapolis, Indiana2; Oregon Health and Science University, Portland, Oregon3
Introduction: Colon capsule endoscopy (CCE) is a new endoscopic capsule for visualization of the colon. The capsule is 31x11mm. It has two imagers and obtains 4 frames per second. It is not a FDA approved device. A blinded trial was being performed to assess the feasibility and efficacy of this technology in screening patients at risk for colon polyps and cancer.
Materials and Methods: At risk volunteers were recruited. Study entry required age over 50 and not having colonoscopy within 5 years or having a family history of colon cancer or the presence of symptoms suspicious for cancer. Volunteers were paid and signed IRB approved consent forms. Patients initially underwent CCE and within 3 weeks took a second preparation and underwent virtual (VC) and standard colonoscopy (SC) on the same day. The colonoscopist was blinded to the findings of the previous tests. At SC, results of the two previous tests were serially unblinded. Results were reviewed. Significant findings were defined as any polyp ≥6mm in size or 3 or more polyps of any size.
Inclusion Criteria: Patients between the ages of 50-75
•Indicated for CRC screening, who did not have colonoscopy in last 5 years, OR with current or recent history of IDA
Patients between the ages of 40-75•With family history of colonic polyps or CRC•With FOBT positive
Patients sign an IRB informed consent form
Exclusion Criteria: Dysphagia Known or suspected bowel obstruction High risk for capsule retention and abdominal surgery of the GI tract
within the last six months Contra-indication for any procedure prescribed in the study,
e.g., ingestion of oral sodium phosphate or polyethylene glycol solutions, Tegaserod or Bisacodyl suppository
Congestive heart failure or renal insufficiency or liver disease Cardiac pacemakers or other implanted electro medical-device Pregnancy MRI examination within 7 days after capsule ingestion Current life threatening conditions
Study Overview:• Capsule procedure:
• Day -1: Clear liquids and evening laxative as below• Day 0: Laxatives and prokinetic agents, Capsule ingestion
• Capsule video review by Investigators DR, DL*• Within 3 weeks following Capsule procedure:
• Early morning: Virtual colonoscopy by investigator JM*• Midday: Colonoscopy by investigator BL* then sequential
un-blinding * all investigators blinded to each other
Capsule Colonoscopy Preparation:Day -1 Clear Liquid diet
1800 – 2100 2 Liter PEG
Exam day 700 – 800 1 Liter PEG
815 6mg Tegaserod
830 Capsule ingestion
1040 Boost I (30ml NaP) *
1300 6mg Tegaserod
1400 Boost II (15ml NaP)
1600 Suppository 10mg Bisacodyl - if needed
1700 Regular meal
* Pending verification that the capsule had exited the the stomach using a real-time viewer .
Assessment of Bowel Cleansing:
• Poor - Large amount of fecal residue• Fair - Enough feces or dark fluid present to preclude
a completely reliable examination• Good - Small amount of feces or dark fluid, but not
enough to interfere with examination• Excellent - No more then small bits of adherent feces
Poor Fair Good Excellent
Study Results - Enrollment:• 64 patients screened - 12 failed• 52 enrolled - 1 discontinued• 51 completed trial
-Average age 54 (40-74)-28 Males, 23 Females-31 for screening-16 for family history-3 for blood in stool-1 for personal history of polyps
60%
33%
5%2%
53%
38%
7%3%
59%
35%
4%
57%
33%
11%0%
47%
27%
20%
7%
0%
20%
40%
60%
80%
100%
Ceacum Right Colon Transverse Left Colon Sigmoid-Rectum
Excellent Good Fair Poor
Results - Bowel cleanliness:
Transit Time From Ingestion to Excretion
6%
67%
84% 88% 90%100%
0
5
10
15
20
25
30
35
2:00 4:00 6:00 8:00 10:00 Later
Time [Hours]
Freq
uenc
y
0%
20%
40%
60%
80%
100%
Transit time from ingestion to Transit time from ingestion to excretionexcretion
2%
90%
6%
2%
Results - Capsule Transit:
Capsule Location at 10 hrs
Results - Polyp Detection: Polyps of any size/path were found in 29/51 patients (57%)Polyps of any size/path were found in 29/51 patients (57%)
•60 polyps by un-blinded colonoscopy60 polyps by un-blinded colonoscopy•55 polyps by colonoscopy55 polyps by colonoscopy•94 polyps by capsule colonoscopy94 polyps by capsule colonoscopy•26 polyps by virtual colonoscopy26 polyps by virtual colonoscopy
Adenomatous polyps were found in 15/51 patients (29%)Adenomatous polyps were found in 15/51 patients (29%)•17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm•16/17 detected by standard colonoscopy (1 missed and found on unblinding)16/17 detected by standard colonoscopy (1 missed and found on unblinding)•12/17 detected by capsule12/17 detected by capsule•5/17 detected by virtual colonoscopy5/17 detected by virtual colonoscopy
Results - Sensitivity and Specificity:Colonoscopy Capsule Virtual Colonoscopy
For any polyp
Sensitivity 93% (95% CI, 85-93%) 83% (95% CI, 72-92%) 38% (95% CI, 27-44%)
Specificity 100% (95% CI, 90-100%) 45% (95% CI, 31-57%) 86% (95% CI, 72-95%)
PPV 100% (95% CI, 92-100%) 67% (95% CI, 58-74%) 79% (95% CI, 56-92%)
NPV 92% (95% CI, 82-92%) 67% (95% CI, 46-83%) 51% (95% CI, 43-56%)
For significant findings *
Sensitivity 89% (95% CI, 77-89%) 56% (95% CI, 38-71%) 33% (95% CI, 20-38%
Specificity 100% (95% CI, 93-100%) 76% (95% CI, 66-84%) 97% (95% CI, 90-99%)
PPV 100% (95% CI, 86-100%) 56% (95% CI, 38-71%) 86% (95% CI, 52-97%)
NPV 94% (95% CI, 88-94%) 76% (95% CI, 66-84%) 73% (95% CI, 67-75%)
* Significant findings: Polyps ≥ 6 mm OR three or more polyps of any size
The Capsule:• 11 x 31mm• Wider angle of view• 2 Frames/second from each side• 10 gig recording device
Ø1
1 m
m
31 mm
Virtual Colonoscopy:• "Top CAT” GE 64-detector VCT was used to scan the patients' cleansed colons. • Data was compiled and reviewed in 2D and 3D on a Vitrea workstation.
Colonoscopy:• Performed under conscious sedation (Demerol/Versed)• Complete in all patients• Limited withdrawal time to less than 10 minutes to limit study effect
Polyp seen at colonoscopy Polyp seen on capsule
Conclusions: Colon capsule endoscopy appears to be a promising new technology for screening the colon for polyps in patients at risk for colorectal cancer.
This feasibility study demonstrates that capsule colonoscopy appears to be a safe and promising new technology for visualizing the colon
This capsule colonoscopy may complement traditional colonoscopy for:
•Contraindicated colonoscopy
•Incomplete colonoscopy
•Patients unwilling to undergo standard colonoscopy
Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps
Conclusions: This feasibility study demonstrates that capsule colonoscopy appears to be a safe and
promising new technology for visualizing the colon and for screening the colon for polyps in patients at risk for colorectal cancer
This capsule colonoscopy may complement traditional colonoscopy for:
• Contraindicated colonoscopy
• Incomplete colonoscopy
• Patients unwilling to undergo standard colonoscopy
Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps
8
PCCE: European studiesPCCE: European studies
MA-48 Jacques DevièreMA-48 Jacques DevièreErasme University HospitalErasme University Hospital
First European Feasibility StudyFirst European Feasibility Study
** Endoscopy, Vol. 38, October 2006Endoscopy, Vol. 38, October 2006
9
Feasibility Study ObjectivesFeasibility Study Objectives
Prospective pilot evaluation of the
performance and accuracy parameters of
PillCam COLON Capsule compared with
traditional colonoscopy
Evaluation the efficacy of colon
preparation for colon Capsule endoscopy
10
Inclusion CriteriaInclusion Criteria
Patients between the ages of 18-75 years
Patients suspected of having colonic disease referred for traditional colonoscopy
OR
Patients referred for colonoscopy for CRC screening
11
Exclusion CriteriaExclusion Criteria
All usual contra indication for Small Bowel CE
Patients with high risk for capsule retention:• Crohn's disease, SB tumors, radiation enteritis, NSAID,
surgical anastomosis
Patients with contraindications to ingest oral sodium phosphate or polyethylene glycol solution
Patients with known allergy to Domperidone or Bisacodyl suppository
12
Process OverviewProcess Overview
1. Patient signed informed consent
2. Day -1: Clear liquids and evening laxative
3. Examination daya. Laxative and prokinetic agentsb. Ingestion of PillCam COLONc. Traditional colonoscopy performed by investigator #1* following capsule
excretion or at 19:00d. Patient discharged
4. Capsule video reviewed by Investigator #2*
* Both investigators blinded to each other results.
13
Day -1Clear liquids diet (no breakfast)
1800 – 2100 2 liters PEG
Exam day
700 – 800 1 liter PEG
745-800 20mg Domeperidone and Capsule ingestion
1000 Booster I (45ml NaP) *
1400
* Pending verification that PillCam COLON had moved out of the stomach with RAPID Access RT (real-time viewer)
Traditional colonoscopy prep (clear liquid diet and 4 liters Colopeg®)
55% of patients
Preparation and ProcedurePreparation and Procedure
14
Additional intakes for up to 45% of patients
Day -1Clear liquids diet (no breakfast)
1800 – 2100 2 liters PEG
Exam day
700 – 800 1 liter PEG
745-800 20mg Domeperidone and Capsule ingestion
1000 Booster I (45ml NaP) *
1400
* Pending verification that PillCam COLON had moved out of the stomach with RAPID Access RT (real-time viewer)
Traditional colonoscopy prep (clear liquid diet and 4 liters Colopeg®)
55% of patients
1400 Booster II (30ml NaP)
1500 Optional low-fiber snack
1630 10mg Bisacodyl suppository
1900 Traditional colonoscopy
Preparation and ProcedurePreparation and Procedure
15
Poor Large amount of fecal residue
FairEnough feces or dark fluid present to preclude a completely reliable examination
GoodSmall amount of feces or dark fluid, but not enough to interfere with examination
Excellent No more then small bits of adherent feces
Poor Good ExcellentFair
Preparation and Procedure:Preparation and Procedure:Assessment of Colon CleanlinessAssessment of Colon Cleanliness
16
41 Patients enrolled (26 women, mean age 56 years, range 26-75)
• Three patients out of the first five were excluded from the analysis due to technical capsule failure
• One patient could not swallow the Capsule because of excessive anxiety• In one patient Capsule data compilation failed
Results reported for 36 patients
No adverse events (AE) were reported
Results: Demographics and AEResults: Demographics and AE
17
Patient referred CRC screening 41 %
Patients suspected of having colonic disease 59%
Results: Reasons for ReferralResults: Reasons for Referral
18
Results: PreparationResults: Preparation
Overall preparation for PillCam COLON Capsule• Excellent: 33% of cases
• Good: 58%
• Fair: 6%
• Poor: 3%
All patients tolerated the preparation without any significant complaints
19
ResultsResults Location of Location of Capsule at 10 hours post ingestionCapsule at 10 hours post ingestion
3%
3%
84%
3%
7%
20
ResultsResultsTumor and Polyps DetectionTumor and Polyps Detection
21
Case ICase IS
am
ple
S
am
ple
Cases
Cases
Colonoscopy: Carcinoma at sigmoid, patient referred to surgical intervention
PillCam: Large neoplastic mass at sigmoid
PillCam imageColonoscopy image
22
Case IICase IIS
am
ple
Cases
Sam
ple
Cases
Colonoscopy: Tumor at rectum, patient referred to surgical intervention
PillCam: Large rectal neoplastic mass
PillCam images
23
Case IIICase III
PillCam imageColonoscopy image
Colonoscopy:• 8 mm polyp at sigmoid• 5 mm polyp at transversePillCam:• 6-9 mm polyp at sigmoid
Sam
ple
Cases
Sam
ple
Cases
24
PillCam images
Case VICase VI
Colonoscopy: Normal
PillCam: Two polyps (<6 mm) at descending colon
Sam
ple
Cases
Sam
ple
Cases
25
Polyp Findings of Capsule COLON Endoscopy Polyp Findings of Capsule COLON Endoscopy (CCE) and Traditional Colonoscopy(CCE) and Traditional Colonoscopy
*
CCE identified 19 of 25 patients (76%) with positive findings CCE identified 10 of 13 patients (77%) with significant lesions* 2 tumors were detected by both methods
26
Findings of Capsule COLON Endoscopy (CCE) vs. Findings of Capsule COLON Endoscopy (CCE) vs. Traditional ColonoscopyTraditional Colonoscopy
Polyps > 6 mm
Polyps > 6 mm or ≥ 3 polyps
Any kind of polyps
Sens Spec PPV NPV
% 76% 64% 83% 54%
95% CI, % 59-93 35-92 67-98 27-81
% 77% 71% 59% 84%
95% CI, % 54-100 41-88 35-82 68-100
% 60% 73% 46% 83%
95% CI, % 30-90 56-90 19-73 67-98