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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P140008 / PAS001 |
| Date Original Protocol Accepted |
02/26/2016
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| Date Current Protocol Accepted |
11/28/2018
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| Study Name |
ORBERA PAS (OPAS-001)
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| Device Name |
ORBERA INTRAGASTRIC BALLOON
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
This is a prospective, multicenter, open-label new enrollment post-approval study of the safety and effectiveness of ORBERA as an adjunct to weight reduction for obese adults (22 years of age and older) with a Body Mass Index (BMI) of greater than or equal to 30 kg/m2 and BMI of less than or equal to 40 kg/m2. Treatment includes behavioral modification program in conjunction with endoscopic placement of a single ORBERA Intragastric Balloon, filled with saline to an inflation volume between 400cc and 700cc, for 26 weeks followed by endoscopic ORBERA removal.
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| Study Population |
Male and female subjects, 22 years of age and older, with a BMI of greater than or equal to 30 kg/m2 and less than or equal to 40 kg/m2 who have failed more conservative weight- reduction alternatives, such as supervised diet, exercise, and behavioral modification programs will be enrolled into this study.
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| Sample Size |
Up to 284 subjects will be enrolled to yield approximately 255 subjects treated with the ORBERA. Sample size calculations were performed for the primary objective and the key secondary effectiveness objective, with the sample size being driven by the primary objective. Approximately 255 subjects will be treated with the device and will provide 80% power to demonstrate that the device and procedure-related serious adverse event rate is <15%, assuming the rate is no more than 5% than what was observed in the pivotal study. Assuming 255 subjects are treated with ORBERA with an attrition rate of 10% during treatment, there will be approximately 230 subjects completing 26 weeks of treatment. This will provide greater than 99% power to demonstrate that the observed mean %TBWL is more than 7.5% after 26 weeks of ORBERA treatment.
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| Key Study Endpoints |
The primary endpoint is the incidence of device and procedure-related SAEs after 26 weeks of ORBERA treatment.
Secondary Effectiveness Endpoints:
Mean %TBWL at study week 26
%TBWL at each post-placement visit
%EWL at each post-placement visit
Change from baseline in BMI at each visit
Response to ORBERA™ treatment
Change in satiety using the SNAQ
Subject Satisfaction
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| Follow-up Visits and Length of Follow-up |
Evaluations while on treatment will be performed at baseline (pre-placement), Day 0 (ORBERA™ placement), Day 2 phone call, and eight (8) regularly scheduled clinic visits while on device treatment at study weeks 1, 2, 4, 8, 12, 16, 20, and 24. Device removal will occur at 26 study weeks. If device is removed earlier than 26 weeks, the visits will continue in accordance with the study week visits specified during treatment. Reasons for early removal may include, but are not limited to, an adverse event, subject dissatisfaction or achievement of weight loss goal. Seven (7) clinic visits will occur during the weight loss maintenance follow-up period at study weeks 28, 32, 36, 40, 44, 48, and 52 (study exit).
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
284
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| Actual Number of Sites Enrolled |
12
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| Patient Follow-up Rate |
> 90%
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| Final Safety Findings |
Primary Endpoint: The incidence of device and procedure-related serious adverse events (SAEs) after balloon treatment among available subjects (hypothesis SAEs < 15%). SAEs incidence: 8.9% (23/257), upper limit of 1-sided 95% confidence interval: 12.4% (p-value = 0.0033).
Body System / Preferred Term Incidence Rate %
N = 257
Gastrointestinal Disorders 7.8
Abdominal Distension 0.4
Abdominal Pain 1.9
Diarrhea 0.8
Epigastric Discomfort 0.8
Gastroesophageal Reflux Disease 0.4
Impaired Gastric Emptying 1.9
Nausea 2.7
Vomiting 4.7
Metabolism and Nutrition Disorders 0.8
Dehydration 0.4
Hypokalemia 0.4
Device Malfunction 1.6
Hyperinflation of Balloon 1.6
Adverse Events: 62.8% subjects (162/258)
87% device related
10% procedure related
58% mild
9% severe
1% erosive gastritis
1% gastric ulcers
1 incidental partial deflation reported at the time of balloon removal
1 esophageal mucosal tear was repaired during the procedure with no additional sequelae
No deaths, pancreatitis gastric perforation, esophageal perforation or esophageal ulcers
Early removal: 47(18%)
AEs related to symptoms associated with gastrointestinal intolerance were: abdominal pain, dyspepsia, epigastric discomfort, gastroesophageal reflux disease, impaired gastric emptying, nausea, retching and vomiting accounted for 71% of all device-related AEs (65% were mild, 80% moderate and 80% severe).
Device related AEs were associated with gastrointestinal intolerance that resolved between 0 to 29 weeks, 90% resolved with no treatment or medication, and over 64% resolved within 2 weeks of onset.
Device deficiencies: 16 (6%)
10 subjects had device malfunctions (9 device related and 1 due to trauma). Six subjects have technical issues with a feature of the balloon system during placement or removal. None resulted in injury or needed an aborted procedure.
Device Removal: 210 subjects (81%) completed the 26-week treatment period prior to device removal, 9 of them had their initial removal aborted due to excess food found in the stomach without having AEs. The second removal attempts were completed with no issues.
Additional Safety Data: 6 out of 258 patients (2%) had balloon hyperinflation with onset of symptoms from within 1 to 23 weeks after balloon placement. Symptoms include nausea, vomiting, and abdominal pain. In 4 of the 6 cases, symptoms prompted the early removal of the balloons, 1 patient had balloon removed emergently at week 24, and in the last one, balloon hyperinflation was found at removal time with no symptoms.
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| Final Effect Findings |
%Total Body Weight Loss: %TBWL = 100(weight of post-placement visit – baseline weight) / baseline weight.
%TBWL Mean
Completers Population: -13
Efficacy Population: -13
Full Analysis Population: -12
Multiple Imputation: -13
%TBWL
Week Mean by visit
1: -4
2: -4
4: -6
12: -9
24: -11
36: -10
52: -8
% Excess Weight Loss: %EWL = 100 (weight of post-placement visit – baseline weight) / excess weight
%EWL
Week Mean by visit
1: 14
2: 17
4: 23
12: 34
24: 41
36: 38
52: 31
Simplified Nutrition Assessment Questionnaire (SNAQ) by Visit as % of subjects with reduced appetite (score < 14)
Week % Subjects with SNAQ < 14 (N =258)
Baseline 10
1: 77
2: 65
4: 49
12: 25
24: 24
36: 14
52: 15
Subject Satisfaction
A treatment experience was applied in the 8-week through the 24-week follow-up visits, and a satisfaction questionnaire was applied at the exit visit.
Satisfaction Questionnaire Summary by Visit Type (Selected Response) N = 247
Response 24 Weeks
Overall, how would you rate your experience with ORBERA®?
Category %
Excellent: 21
Very Good: 24
Good: 26
Fair: 19
Poor: 9
Exit Satisfaction Questionnaire Summary (Selected Responses) N = 245
Overall, how would you rate your experience with ORBERA?
Category %
Excellent: 24
Very Good: 24
Good: 22
Fair: 18
Poor: 11
Overall, given your recent experience with ORBERA®, if you had to do it all over again, would you choose ORBERA?
Category %
Definitely: 36
Probably: 20
Not sure: 11
Probably not: 16
Definitely not: 17
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| Study Strengths & Weaknesses |
Strengths: Sample size adequate and power over 90% for the overall analysis. Follow up rate over 90% for all follow-up visits.
Weaknesses: No comparator was included and not enough sample size for BMI safety subgroup analysis.
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| Recommendations for Labeling Changes |
Yes, including the design, methods and results of the post-approval study.
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