Safety and Efficacy of EndoBarrier in Subjects With Type 2 Diabetes Who Are Obese (ENDO)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Up to 500 subjects were planned to be randomized into either the EndoBarrier or the sham control arm at a 2:1 ratio, respectively. Due to early termination of the trial, only 325 subjects were randomized with 216 EndoBarrier subjects and 109 sham control subjects.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The mITT population for the primary analyses includes 213 EndoBarrier subjects and 107 sham control subjects. The remaining five (5) subjects (n=3 randomized to device; n=2 randomized to sham) were deemed ineligible before an attempted device placement due to findings identified during the upper endoscopy.

Reporting Groups

	Description
EndoBarrier Group	Subjects randomized to the device group received the EndoBarrier Gastrointestinal Liner. Subjects also received a prophylactic dose of antibiotics on Procedure Day. Fluoroscopy was also used in conjunction with endoscopy to aid implantation of the EndoBarrier device. Medical Nutritional Therapy (MNT) counseling (as defined by the 2012 American Diabetes Association guidelines) was to be conducted at Baseline then Weeks 13, 26, 39, and 52 for both groups, and additionally at Week 65 for the EndoBarrier group.
Sham Control Group	Subjects randomized to the sham control group also underwent an upper endoscopy (without fluoroscopy) according to standard institutional endoscopy practices. Subjects also received a prophylactic dose of antibiotics on Procedure Day.Medical Nutritional Therapy (MNT) counseling (as defined by the 2012 American Diabetes Association guidelines) was to be conducted at Baseline then Weeks 13, 26, 39, and 52.

Participant Flow:   Overall Study

	EndoBarrier Group	Sham Control Group
STARTED	213 [1]	107 [2]
COMPLETED	52 [3]	60 [4]
NOT COMPLETED	161	47
Sponsor Terminated Study	106	35
Withdrawal by Subject	16	9
Adverse Event	13	0
Procedure/device failure	7	0
Lost to Follow-up	9	2
Physician Decision	2	0
Subject Non-Compliance	2	0
Inter-current finding at procedure	1	0
Incorrectly enrolled in Study	0	1
various not noted previously	5	0

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

	Description
EndoBarrier Group	Subjects randomized to the device group received the EndoBarrier Gastrointestinal Liner. Subjects also received a prophylactic dose of antibiotics on Procedure Day. Fluoroscopy was also used in conjunction with endoscopy to aid implantation of the EndoBarrier device.
Sham Control Group	Subjects randomized to the sham control group also underwent an upper endoscopy (without fluoroscopy) according to standard institutional endoscopy practices. Subjects also received a prophylactic dose of antibiotics on Procedure Day.
Total	Total of all reporting groups

Baseline Measures

	EndoBarrier Group	Sham Control Group	Total
Overall Participants Analyzed  [Units: Participants]	213	107	320
Age [1]  [Units: Years] Mean (Standard Deviation)	52.9  (8.19)	51.8  (8.21)	52.5  (8.20)
[1] Age, range 25 to 65 years
Gender [1]  [Units: Participants] Count of Participants
Female	127  59.6%	69  64.5%	196  61.3%
Male	86  40.4%	38  35.5%	124  38.8%
[1] In both arms (Device and Sham) of the mITT population, 61.3% were female and 38.8% were male
Ethnicity (NIH/OMB)  [Units: Participants] Count of Participants
Hispanic or Latino	19   8.9%	14  13.1%	33  10.3%
Not Hispanic or Latino	194  91.1%	93  86.9%	287  89.7%
Unknown or Not Reported	0   0.0%	0   0.0%	0   0.0%
Race/Ethnicity, Customized [1]  [Units: Participants]
American Indian or Alaska Native	6	3	9
Asian	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	44	22	66
White	165	80	245
More than one race	1	1	2
Unknown or Not Reported	1	1	2
[1] Subjects were allowed to select more than one race.
Baseline Weight (lbs)  [Units: Lbs] Mean (Standard Deviation)	245.0  (47.46)	245.6  (44.20)	245.2  (46.32)
Baseline BMI  [Units: Kg/m2] Mean (Standard Deviation)	38.4  (5.74)	38.3  (5.33)	38.4  (5.60)
HbA1c (%) fasting bloodwork  [Units: Percent] Mean (Standard Deviation)	8.8  (0.92)	8.9  (0.89)	8.8  (0.91)

1.  Primary:

Primary Efficacy Endpoint: Improvement in HbA1c   [ Time Frame: Baseline and12 months ]

2.  Primary:

Primary Safety Endpoint: Early Device Removal Due to Device-Related SAE   [ Time Frame: Baseline and 12 Months ]

3.  Secondary:

Assessment of Total Cholesterol Change at 12 Months Compared to Baseline   [ Time Frame: Baseline and 12 Months ]

4.  Secondary:

Percentage of Subjects Who Achieve HbA1c Less Than or Equal to 7.0% at 12 Months   [ Time Frame: Baseline and 12 Months ]

5.  Secondary:

LDL Change From Baseline   [ Time Frame: Baseline and 12 Months ]

6.  Secondary:

Triglycerides Change From Baseline   [ Time Frame: Baseline and 12 Months ]

7.  Secondary:

Fasting Glucose Change From Baseline   [ Time Frame: Baseline and 12 Months ]

8.  Secondary:

Systolic BP Change From Baseline   [ Time Frame: Baseline and 12 Months ]

9.  Secondary:

Diastolic BP Change From Baseline   [ Time Frame: Baseline and 12 Months ]

10.  Secondary:

Percentage of Subjects Who Achieve % Total Body Weight Loss Greater Than or Equal to 5% at 12 Months   [ Time Frame: Baseline and 12 Months ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The ENDO Trial was stopped early due to a higher than anticipated rate of hepatic abscess (n=7).