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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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REDUCE PAS


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General
Study Status Terminated
Application Number P140012 / PAS001
Date Current Protocol Accepted 05/30/2018
Study Name REDUCE PAS
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group Device Subjects Serve as Own Control
Analysis Type Analytical
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description The primary study objective is to demonstrate the safety of the

ReShape Dual Balloon treatment using a composite endpoint consisting of all device- and/or procedure-related serious adverse events (SAEs) including those associated with early device explants or deflations, gastric ulcers and esophageal trauma.



The study design is a prospective, new-enrollment, multicenter, single arm, open label clinical study.

Study Population Description Patients intending to have the ReShape procedure will be recruited

to include men and women 22 years of age and older with BMI =

30kg/m2 and = 40kg/m2 with one or more obesity-related

comorbidities.



The device group will act as its own comparator, with the device being removed after 24 weeks.

Sample Size 250 Intention to treat (ITT)/safety subjects will be enrolled at 10-15 sites in the US only (including ~4 from the pivotal trial sites) in order to have 223 weight-loss completed subjects at 24 weeks post device insertion and 182 weight-loss completed subjects at 48 weeks post- device insertion.



Assumptions:

CSE rate = 7.5% in REDUCE pivotal trial;

With a 1-sided upper confidence bound (UCB) of 0.975 and performance goal of 13%, an 80% power and normal approximation CIs result in an estimated sample size of 217 subjects.

Precision estimates/Confidence bounds for descriptive assessments:

1. % excess weight loss (%EWL) at 24 weeks:

Assuming an ITT 25.0 ± 21.0%EWL at 24 Weeks, a sample size of 250 will

provide a precision on the estimate of %EWL of 3.0 % with > 99% probability. For the Completer Cohort (n = 223) the precision will be 3.5% with > 99% probability.

2. % total body weight loss (%TBL) at 24 weeks:

Assuming an ITT 7.5 ± 5.5%TBL at 24 Weeks, a sample size of 250 will provide a precision on the estimate of %TBL of 1.0% with > 99% probability. For the Completer Cohort (n = 223) the precision will be 1.0% with > 99% probability.

3. Rate of gastric ulceration through the date of device retrieval: Assuming a rate of any device-related gastric ulceration of 10.5% using the modified tip (commercialized) device based on the REDUCE Pivotal and Single Arm studies,

a sample size of 250 will provide an exact binomial UCB of 14.9%

4. Rate of deflations through the date of device retrieval: Assuming a rate of any device deflation of 6.0% based on the REDUCE Pivotal Trial, a sample size of 250 will provide an exact binomial UCB of 9.7%

5. Rate of early retrievals: Assuming a rate of any retrieval occurring before

154 days of 15.0% based on the REDUCE Pivotal Trial, a sample size of 250

will provide an exact binomial UCB of 19.8%

6. Training and real world performance: for the comparison of safety rates between REDUCE Pivotal Trial (n=265) and ReShape PAS (n=250) a sample size of 250 subjects will achieve a precision of 6.5% or less with > 99% probability for the safety rates of interest (early retrievals and procedure- related SAEs).

*Note: subgroup assessments will be performed for the following: Extended Treatment subjects, Subjects Older Than Sixty, Obesity Drug Treatment subjects, subjects dichotomized by received fill volume (900cc/750cc), subjects dichotomized by age (<45, =45 years), subjects dichotomized by baseline BMI (<35kg/m2,

=35kg/m2) and sex, age and baseline BMI (<35kg/m2, = 35kg/m2)

Data Collection The primary safety endpoint is a composite of certain device- or procedure-related SAEs – CSE to include:

Any gastric ulcer SAE, any esophageal injury SAE, any device-related SAE (including those SAEs associated with deflations), any insertion/retrieval procedure-related SAE (including those SAEs associated with early retrievals).



The secondary/additional safety endpoints include:

1. The rates of each individual CSE component

2. Rate of all device retrievals prior to day 154

3. Rate of device deflations

4. Rate of all device-related gastric ulcers, SAE and non-SAE

5. Analysis of accommodative symptoms of nausea, vomiting, and/or abdominal pain using the prospective Rhodes Index of Nausea, and Abdominal Pain Visual Scale instruments.



There is no primary effectiveness endpoint



The secondary/additional effectiveness endpoints include:

1. Intent-To-Treat (with multiple imputation – ‘MI’) as last- observation-carried-forward (LOCF) – (for missing data) and Completed Cases weight loss characterization at weeks 24 and

48 (%EWL, %TBL, pounds lost and BMI unit reduction using all available data, and for 48 week data, comparison to 24 week values)

2. Subject satisfaction survey, Impact of Weight on Quality of Life

(IWQoL) and Three Factor Eating Questionnaire (TFEQ) at weeks

24, and 48.

Follow-up Visits and Length of Follow-up Virtual visits may be allowed for Week 1, 4, 8, 12, 16, 20, 28, 32, 36, 40, and 44. During these visits, the subjects will submit their weight via the Patient Portal. A full assessment will be done over the phone by the Study Doctor or designee. Blood pressure measurement will be optional for these visits.

Interim or Final Data Summary
Actual Number of Patients Enrolled The study was terminated early due to voluntary market withdrawal of the device by the sponsor for business reasons. 187 subjects were enrolled and 159 device implants were attempted, 152 subjects received the device.
Actual Number of Sites Enrolled 15
Patient Follow-up Rate 97.4% (148/152) at Week 1; 80.3% (122/152) at Week 12; 82.9% (126/152) at Week 24; 42.1% (64/152) at Week 36; 36.2% (55/152) at Week 48
Final Safety Findings Primary Safety Endpoint

Composite Safety Endpoint (CSE)

The CSE includes any device- or procedure-related gastric ulcer SAE, any device- or procedure-related esophageal injury SAE, any other device-related SAE (including those SAEs associated with deflations), any other procedure-related insertion/retrieval SAE (including those SAEs associated with early retrievals).

Of the 159 subjects who were enrolled and device implant was attempted, twelve (12) had missing removal data. Therefore, the CSE was considered for the subjects with data (N=147, “available cases”), a best-case scenario where no CSE adverse events occurred in the subjects for which there is missing data, and a worst-case scenario where CSE adverse events occurred in all subjects for which there is missing data.

Available Cases: 8.8% (13/147) with one-sided 97.5% upper confidence bound of 13.4%

Best-Case Scenario: 8.2% (13/159) with one-sided 97.5% upper confidence bound of 12.4%

Worst-Case Scenario: 15.7% (25/159) with one-sided 97.5% upper confidence bound of 21.4%

The hypothesis test for the primary endpoint was based on an estimated sample size of 217 subjects. Given the actual sample size of 159 subjects, the power is 61%.

Secondary/Additional Safety Endpoints

The rates of each individual CSE component

Any gastric ulcer SAE rate: 0.6% (1/159), 95% CI: 0.0, 1.9%

Any esophageal injury SAE rate: 0.6% (1/159), 95% CI: 0.0, 1.9%

Any other device-related SAE rate: 6.9% (11/159) 95% CI: 3.0, 10.9%

Any other procedure-related SAE rate: 1.3% (2/159), 95% CI: 0.0, 3.0%

Additional Safety Data

One event of procedure-related pancreatitis reported: 0.6% (1/159); and two events of device-related pancreatitis reported: 1.3% (2/159).

One event of procedure-related pneumonia aspiration reported: 0.6% (1/159)

No events of gastric or esophageal perforation reported

No events of death reported

No events of spontaneous hyperinflation reported

Rate of all device retrievals prior to day 154

There were 23 early device retrievals (15.1%; 23/152), 95% CI: 9.4, 20.8%

Rate of device deflations

There were six (6) device deflations (3.9%; 6/152), 95% CI: 0.9, 7.0%

Rate of all device-related gastric ulcers, SAE and non-SAE

Device or procedure related gastric ulcer rate: 4.4% (7/159) with one-sided 95% upper confidence bound of 7.6%; one (1) was an SAE: 0.6% (1/159); and six (6) events were non-SAE.

Analysis of accommodative symptoms of nausea, vomiting, and/or abdominal pain using the prospective Rhodes Index of Nausea, and Abdominal Pain Visual Scale instruments

Rhodes Index of Nausea, Vomiting and Retching, as well as Abdominal Pain VAS, were evaluated in subjects at baseline, Week 1, Week 4, Week 12, and Week 24. The Rhodes overall score increased with severity of symptoms. Results showed increased overall score from baseline at Week 1, approximately 6.3 times that of baseline, and at Week 4, approximately 3 times that of baseline. Scores were comparable to baseline following Week 4.

Abdominal Pain Visual Scale showed substantial increase from baseline through Week 1 for all subjects, approximately 10% increase in pain level. The overall pain level decreased by Week 4 to less than 3% (or 2% below baseline level).
Final Effect Findings No Primary Effectiveness Endpoint

Secondary/Additional Effectiveness Endpoints

Intent-To-Treat (with multiple imputation – ‘MI’) as last- observation-carried-forward (LOCF) – (for missing data) and Completed Cases weight loss characterization at weeks 24 and 48 (%EWL, %TBL, pounds lost and BMI unit reduction using all available data, and for 48 week data, comparison to 24 week values)

Week 24 Data

Completed Case (N=126): Mean (SD) (Min, Max)

%EWL: 36.22% (23.42%) (-4.8%, 112.7%)

%TBL: 10.06% (6.06%) (-1.2%, 24.1%)

Weight Loss (lbs): 22.04 (14.16) (-2.3, 62.9)

BMI Loss (kg/m2): 3.58 (2.20) (-0.4, 9.3)

LOCF (N=159): Mean (SD) (Min, Max)

%EWL: 32.69% (23.49%) (-4.8%, 112.7%)

%TBL: 8.90% (6.14%) (-1.2%, 24.1%)

Weight Loss (lbs): 19.29 (14.17) (-2.3, 62.9)

BMI Loss (kg/m2): 3.14 (2.22) (-0.4, 9.3)

Worst Case (N=159) assumes no weight change for subject not evaluated at 24 weeks: Mean (SD) (Min, Max)

%EWL: 28.71% (25.52%) (-4.8%, 112.7%)

%TBL: 7.97% (6.77%) (-1.2%, 24.1%)

Weight Loss (lbs): 17.46 (15.46) (-2.3, 62.9)

BMI Loss (kg/m2): 2.83 (2.44) (-0.4, 9.3)

The study was terminated prior to achieving full enrollment. Due to this, and subjects lost to follow-up, only 53 subjects completed the 48-week follow up and had weight data available for Week 24.

Completed Case at Week 24 who also had Week 48 data (N=53): Mean (SD) (Min, Max)

%EWL: 45.82% (25.06%) (-0.3%, 112.7%)

%TBL: 12.60% (6.09%) (-0.1%, 24.1%)

Weight Loss (lbs): 27.81 (14.93) (-0.3, 62.9)

BMI Loss (kg/m2): 4.48 (2.24) (-0.1, 9.3)

Completed Case at Week 48 who also had Week 24 data (N=53): Mean (SD) (Min, Max)

%EWL: 40.80% (28.78%) (-16.5%, 109.7%)

%TBL: 11.25% (7.76%) (-3.1%, 29.9%)

Weight Loss (lbs): 24.77 (18.66) (-6.9, 81.1)

BMI Loss (kg/m2): 4.02 (2.92) (-1.0, 12.0)

Difference in Week 24 and Week 48 data (N=53): Mean (SD) (Min, Max)

%EWL: -5.03% (20.81%) (-62.2%, 48.1%)

%TBL: -1.35% (5.17%) (-13.3%, 8.6%)

Weight Loss (lbs): -3.05 (11.25) (-6.2, 18.2)

BMI Loss (kg/m2): -0.46 (1.80) (-4.2, 2.7)

Subject satisfaction survey, Impact of Weight on Quality of Life (IWQoL) and Three Factor Eating Questionnaire (TFEQ) at weeks 24, and 48

Subject satisfaction surveys were provided to subjects at Week 24 and Week 48. The survey requested a response to three different questions. Over 60% of the subjects were satisfied with their experience with the ReShape balloon at Week 24 and would choose to repeat the process again. The percent satisfaction remained approximately the same at Week 48 based on the limited number of subjects who completed this study time point.

Impact of weight on quality of life (IWQoL-Lite) was assessed by subjects at baseline, Week 24 and Week 48. Quality of life is assessed in five areas: physical function, self-esteem, sexual life, public distress and work. While all scales demonstrated positive changes from baseline, the largest changes were observed in the physical function and self-esteem scales.

Three factor eating (TFEQ-R18v2) was assessed by subjects at baseline, Week 24 and Week 48. The questionnaire characterizes eating behavior in three different domains: cognitive restraint, uncontrolled eating, and emotional eating. All domains demonstrated positive changes from baseline.
Study Strengths & Weaknesses This was a prospective study of newly enrolled and treated patients in the US.

There was no concurrent comparison group, which limits interpretation of the results.

The study did not complete enrollment resulting in a lower sample size than expected.

82.9% of treated subjects were evaluable at the 24 Week point when the device was removed. However, only 36.2% of the subjects were available at Week 48 which limits the interpretation of the study results. The subjects that remained in the study may be different than those that were lost to follow-up, and therefore, the generalizability of results can be limited.
Recommendations for Labeling Changes Not applicable. As of January 1, 2019, the sponsor stopped selling and distributing the device.


REDUCE PAS Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
one year report 07/27/2016 07/27/2016 On Time
18 month report 01/25/2017 01/27/2017 Overdue/Received
two year report 07/27/2017 07/28/2017 Overdue/Received
interim report 04/30/2018 05/01/2018 Overdue/Received
three year report 07/27/2018 07/30/2018 Overdue/Received
42 month report 01/25/2019 01/22/2019 On Time
final report 09/06/2019 09/05/2019 On Time


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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