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444 A Randomized, Multi-Center Study to Evaluate the Safety and Effectiveness of an Intragastric Balloon As an Adjunct to a Behavioral Modification Program, in Comparison With a Behavioral Modification Program Alone in the Weight Management of Obese Subjects
Abstracts Association of Each Genotype of GPBAR1 rs1154825 with Characteristics and GI Quantitative Traits GPBAR1 rs11554825 Data show mean SE TT CT CC N 94 108 53 2 33.30.5 33.50.5 31.80.7 BMI, kg/m Body weight, kg 93.91.7 95.91.6 91.62.3 Satiation (MTV), ml 134542.4 127939.3 115456.7 Fasting ghrelin, pg/ml 74.76 71.85.5 81.68 Postprandial ghrelin (90min), pg/ 301.7 31.51.5 37.32.2 ml Postprandial CCK (45min), pg/ml 6.50.6 8.70.5 6.80.8 Postprandial CCK (AUC), pg/ml 5.80.4 6.80.3 5.30.5 Postprandial GLP-1 (45min), 14.10.8 17.10.8 15.11.1 pmol/L Postprandial GLP-1 (AUC), pmol/L 12.40.6 13.90.5 12.30.8 Postprandial PYY (45min), pg/ml 126.44.5 137.34.1 134.46.1 Postprandial PYY (AUC), pg/ml 125.54.5 129.44.1 124.16 Fasting FGF-19, pg/ml 52.917.5 76.426.7 155.732.7 Postprandial FGF-19 (AUC), pg/ml 45.715 80.117.4 133.421.3
represents a minimally-invasive and effective approach to manage obesity and associated co-morbidities. p value
0.07 0.11 0.03 0.09* 0.005* 0.01 0.03 0.03* 0.1 ns ns 0.06* 0.03*
* Z Nonparametric distribution (tested using Kruskal-Wallis test); ns Z not significant
444 A Randomized, Multi-Center Study to Evaluate the Safety and Effectiveness of an Intragastric Balloon As an Adjunct to a Behavioral Modification Program, in Comparison With a Behavioral Modification Program Alone in the Weight Management of Obese Subjects Barham K. Abu Dayyeh*1, Laura L. Eaton2, George Woodman3, Mark Fusco4, Vafa Shayani5, Helmuth T. Billy6, Anita Courcoulas7, Daniel J. Pambianco8, Christopher J. Gostout1 1 Mayo Clinic, Rochester, MN; 2Apollo Endosurgery, Austin, TX; 3MidSouth Bariatric, Memphis, TN; 4LifeShape Bariatrics, Melbourne, FL; 5 St James Hospital, Olympia Fields, IL; 6Ventura Advanced Surgical Associates, Ventura, CA; 7Magee Women’s Hospital of Univestiy of Pittsburgh Medical Center, Pittsburgh, PA; 8Charlottesville Medical Research, Charlottesville, VA Background & Aims: Obesity have reached epidemic proportions. Bariatric surgical approaches alone are unlikely to meet the increasing burden of disease, and obese patients rarely achieve long-term effective weight loss with only lifestyle interventions. The Orbera Intragastric Balloon System may offer an accessible and useful adjunct to life-style modification in the management of mild to moderate obesity. We performed a randomized, multi-center US study to evaluate the safety and efficacy of the Orbera Intragastric Balloon System. Methods: After a run-in period with the Orbera implanted in 35 obese subjects, 273 obese subjects were randomly assigned (1:1) to groups that underwent Orbera implantation and behavioral management program (BMP) (n Z 137) or BMP alone (n Z 136). Of the 137 subjects assigned to Orbera and BMP, 12 were excluded due to findings at implantation endoscopy or screen failure after randomization leaving 125 subjects (89.6% female, mean age 38.7 9.4 y, mean body mass index (BMI) 35.2 3.17 kg/m2, mean excess weight (EW) 28.4 10.0 kg) in this group. Of the 136 subjects assigned to BMP alone, 6 dropped out after randomization leaving 130 patients (90% female, mean age 40.8 9.6 y, mean BMI 35.4 2.7 kg/m2, mean EW 28.7 8.1 kg) in this group. Subjects were followed for 52 weeks (26 weeks after Orbera explanation). Results: Ninety eight of the 125 subjects (78.4%) who underwent Orbera and BMP treatment and 93 of the 130 subjects (71.5%) who underwent BMP alone completed the 52 weeks of the study. At 26 weeks (balloon removal), 71.8% of the Orbera and BMP subjects achieved R 25% excess weight loss (EWL) with a mean percent total body weight loss (%TBL) for the group of 10.5% 6.6 compared to 31.9% of subjects in the BMP alone group achieving R 25% EWL with a mean %TBL of 4.7% 5.1 (p ! 0.001 on an intention to treat (ITT) analysis). At 52 weeks (26 weeks after balloon removal), 45.9% of the Orbera and BMP subjects achieved R 25% excess weight loss (EWL) with a mean %TBL for the group of 7.7% 7.65 compared to 32.6% of subjects in the BMP achieving R 25% EWL with mean %TBL of 3.9 6.1 (p ! 0.001 on ITT analysis). Furthermore, 43% [95% CI 33% - 53.3%] of Orbera and BMP subjects experienced R15% EWL over the mean %EWL of the BMP group alone at 52 weeks. Both groups had a decrease in the severity of comorbid conditions (diabetes, hypertension, and dyslipidemia) from baseline with the Orbera group showing greater improvement in eating behaviors and weight related quality of life. No deaths or unanticipated device related adverse events were observed. Conclusions: The Orbera Intragastric Balloon System produces significant weight loss that is preserved even after device removal with favorable safety profile. This
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445 The TOUCHSTONE Study: a Randomized, Double-Blind, PlaceboControlled Induction Trial of an Oral S1P Receptor Modulator (RPC1063) in Moderate to Severe Ulcerative Colitis William Sandborn*3, Brian G. Feagan4, Douglas C. Wolf5, Geert R. D’Haens6, Severine Vermeire7, Stephen B. Hanauer8, Subrata Ghosh2, Heather Smith1, Matt Cravets1, Paul A. Frohna1, Sheila Gujrathi1, Allan Olson1 1 Receptos, Inc., San Diego, CA; 2University of Calgary, Calgary, AB, Canada; 3University of California San Diego, San Diego, CA; 4University of Western Ontario, London, ON, Canada; 5Atlanta Gastroenterology Associates, Atlanta, GA; 6Academic Medical Centre, Amsterdam, Netherlands; 7University of Leuvin, Leuven, Belgium; 8Northwestern University Feinberg School of Medicine, Chicago, IL Background: RPC1063 is an oral, selective sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator in clinical development for the treatment of ulcerative colitis (UC) and relapsing multiple sclerosis. Objectives: To evaluate the efficacy of 0.5 mg (low dose, LD) and 1.0 mg (high dose, HD) RPC1063 in comparison to placebo (PBO), and characterize the safety of RPC1063 in patients with moderate to severe UC. Methods: This was an international, 8-week induction trial in moderate to severe UC (defined as a Mayo score of 6-12 with an endoscopic sub-score R2), with a continuing maintenance period for responders. 197 patients were randomized (1:1:1) and treated once daily with PBO (nZ65), LD (nZ65) or HD (nZ67). The primary endpoint was the proportion of subjects in remission (Mayo score %2, no subscore O1) at Wk 8. Secondary endpoints were the proportion of patients in response (reduction in Mayo score of R3 and R30 % with a decrease in the rectal bleeding score of R1 or a rectal bleeding score %1), proportion of patients with mucosal improvement (endoscopy score %1), and the change in Mayo score. Safety assessments included ECG, Holter monitoring, pulmonary function testing, optical coherence tomography and adverse events (AEs). Results: 95% of patients completed the induction portion of the study. The proportion of patients achieving clinical remission was 16.4% for HD (pZ0.0482 vs. PBO), 13.8% for LD (pZ0.1422), and 6.2% for PBO. The proportion of patients with clinical response was 58.2% for HD (pZ0.0140), 53.8% for LD (pZ0.0648), and 36.9% for PBO. The proportion of patients with mucosal improvement was 34.3% for HD (pZ0.0023), 27.7% for LD (pZ0.0348), and 12.3% for PBO. The improvement in Mayo score from baseline was 3.3 points for HD (pZ0.0035), 2.6 points for LD (pZ0.0986), and 1.9 for PBO.The AE profiles were comparable between groups, with approximately 31% of patients experiencing a treatment emergent AE (TEAE) across all groups. The most common TEAEs in the study were worsening of ulcerative colitis (HD 1 [1.5%], LD 2 [3.1%], PBO 3 [4.6%]) and anemia/decreased Hgb (HD 0, LD 3 [4.6%], PBO 3 [4.6%]). Only modest effects on heart rate were seen with no notable cardiac, pulmonary, ophthalmologic or malignancy AEs observed. Transient ALT R3x ULN occurred in 3 patients (HD 1 [1.5%], LD 2 [3.1%]) and decreased with continued treatment. Conclusions: Modulation of S1P receptors in patients with moderate to severe UC with RPC1063 1 mg induced clinical remission, clinical response, and mucosal improvement, validating a novel therapeutic approach for the treatment of UC. The positive efficacy and the safety/tolerability results from this study suggest a favorable risk-benefit profile of RPC1063 that supports a Phase 3 UC program.
Volume 81, No. 5S : 2015 GASTROINTESTINAL ENDOSCOPY AB147
represents a minimally-invasive and effective approach to manage obesity and associated co-morbidities. p value
0.07 0.11 0.03 0.09* 0.005* 0.01 0.03 0.03* 0.1 ns ns 0.06* 0.03*
* Z Nonparametric distribution (tested using Kruskal-Wallis test); ns Z not significant
444 A Randomized, Multi-Center Study to Evaluate the Safety and Effectiveness of an Intragastric Balloon As an Adjunct to a Behavioral Modification Program, in Comparison With a Behavioral Modification Program Alone in the Weight Management of Obese Subjects Barham K. Abu Dayyeh*1, Laura L. Eaton2, George Woodman3, Mark Fusco4, Vafa Shayani5, Helmuth T. Billy6, Anita Courcoulas7, Daniel J. Pambianco8, Christopher J. Gostout1 1 Mayo Clinic, Rochester, MN; 2Apollo Endosurgery, Austin, TX; 3MidSouth Bariatric, Memphis, TN; 4LifeShape Bariatrics, Melbourne, FL; 5 St James Hospital, Olympia Fields, IL; 6Ventura Advanced Surgical Associates, Ventura, CA; 7Magee Women’s Hospital of Univestiy of Pittsburgh Medical Center, Pittsburgh, PA; 8Charlottesville Medical Research, Charlottesville, VA Background & Aims: Obesity have reached epidemic proportions. Bariatric surgical approaches alone are unlikely to meet the increasing burden of disease, and obese patients rarely achieve long-term effective weight loss with only lifestyle interventions. The Orbera Intragastric Balloon System may offer an accessible and useful adjunct to life-style modification in the management of mild to moderate obesity. We performed a randomized, multi-center US study to evaluate the safety and efficacy of the Orbera Intragastric Balloon System. Methods: After a run-in period with the Orbera implanted in 35 obese subjects, 273 obese subjects were randomly assigned (1:1) to groups that underwent Orbera implantation and behavioral management program (BMP) (n Z 137) or BMP alone (n Z 136). Of the 137 subjects assigned to Orbera and BMP, 12 were excluded due to findings at implantation endoscopy or screen failure after randomization leaving 125 subjects (89.6% female, mean age 38.7 9.4 y, mean body mass index (BMI) 35.2 3.17 kg/m2, mean excess weight (EW) 28.4 10.0 kg) in this group. Of the 136 subjects assigned to BMP alone, 6 dropped out after randomization leaving 130 patients (90% female, mean age 40.8 9.6 y, mean BMI 35.4 2.7 kg/m2, mean EW 28.7 8.1 kg) in this group. Subjects were followed for 52 weeks (26 weeks after Orbera explanation). Results: Ninety eight of the 125 subjects (78.4%) who underwent Orbera and BMP treatment and 93 of the 130 subjects (71.5%) who underwent BMP alone completed the 52 weeks of the study. At 26 weeks (balloon removal), 71.8% of the Orbera and BMP subjects achieved R 25% excess weight loss (EWL) with a mean percent total body weight loss (%TBL) for the group of 10.5% 6.6 compared to 31.9% of subjects in the BMP alone group achieving R 25% EWL with a mean %TBL of 4.7% 5.1 (p ! 0.001 on an intention to treat (ITT) analysis). At 52 weeks (26 weeks after balloon removal), 45.9% of the Orbera and BMP subjects achieved R 25% excess weight loss (EWL) with a mean %TBL for the group of 7.7% 7.65 compared to 32.6% of subjects in the BMP achieving R 25% EWL with mean %TBL of 3.9 6.1 (p ! 0.001 on ITT analysis). Furthermore, 43% [95% CI 33% - 53.3%] of Orbera and BMP subjects experienced R15% EWL over the mean %EWL of the BMP group alone at 52 weeks. Both groups had a decrease in the severity of comorbid conditions (diabetes, hypertension, and dyslipidemia) from baseline with the Orbera group showing greater improvement in eating behaviors and weight related quality of life. No deaths or unanticipated device related adverse events were observed. Conclusions: The Orbera Intragastric Balloon System produces significant weight loss that is preserved even after device removal with favorable safety profile. This
www.giejournal.org
445 The TOUCHSTONE Study: a Randomized, Double-Blind, PlaceboControlled Induction Trial of an Oral S1P Receptor Modulator (RPC1063) in Moderate to Severe Ulcerative Colitis William Sandborn*3, Brian G. Feagan4, Douglas C. Wolf5, Geert R. D’Haens6, Severine Vermeire7, Stephen B. Hanauer8, Subrata Ghosh2, Heather Smith1, Matt Cravets1, Paul A. Frohna1, Sheila Gujrathi1, Allan Olson1 1 Receptos, Inc., San Diego, CA; 2University of Calgary, Calgary, AB, Canada; 3University of California San Diego, San Diego, CA; 4University of Western Ontario, London, ON, Canada; 5Atlanta Gastroenterology Associates, Atlanta, GA; 6Academic Medical Centre, Amsterdam, Netherlands; 7University of Leuvin, Leuven, Belgium; 8Northwestern University Feinberg School of Medicine, Chicago, IL Background: RPC1063 is an oral, selective sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator in clinical development for the treatment of ulcerative colitis (UC) and relapsing multiple sclerosis. Objectives: To evaluate the efficacy of 0.5 mg (low dose, LD) and 1.0 mg (high dose, HD) RPC1063 in comparison to placebo (PBO), and characterize the safety of RPC1063 in patients with moderate to severe UC. Methods: This was an international, 8-week induction trial in moderate to severe UC (defined as a Mayo score of 6-12 with an endoscopic sub-score R2), with a continuing maintenance period for responders. 197 patients were randomized (1:1:1) and treated once daily with PBO (nZ65), LD (nZ65) or HD (nZ67). The primary endpoint was the proportion of subjects in remission (Mayo score %2, no subscore O1) at Wk 8. Secondary endpoints were the proportion of patients in response (reduction in Mayo score of R3 and R30 % with a decrease in the rectal bleeding score of R1 or a rectal bleeding score %1), proportion of patients with mucosal improvement (endoscopy score %1), and the change in Mayo score. Safety assessments included ECG, Holter monitoring, pulmonary function testing, optical coherence tomography and adverse events (AEs). Results: 95% of patients completed the induction portion of the study. The proportion of patients achieving clinical remission was 16.4% for HD (pZ0.0482 vs. PBO), 13.8% for LD (pZ0.1422), and 6.2% for PBO. The proportion of patients with clinical response was 58.2% for HD (pZ0.0140), 53.8% for LD (pZ0.0648), and 36.9% for PBO. The proportion of patients with mucosal improvement was 34.3% for HD (pZ0.0023), 27.7% for LD (pZ0.0348), and 12.3% for PBO. The improvement in Mayo score from baseline was 3.3 points for HD (pZ0.0035), 2.6 points for LD (pZ0.0986), and 1.9 for PBO.The AE profiles were comparable between groups, with approximately 31% of patients experiencing a treatment emergent AE (TEAE) across all groups. The most common TEAEs in the study were worsening of ulcerative colitis (HD 1 [1.5%], LD 2 [3.1%], PBO 3 [4.6%]) and anemia/decreased Hgb (HD 0, LD 3 [4.6%], PBO 3 [4.6%]). Only modest effects on heart rate were seen with no notable cardiac, pulmonary, ophthalmologic or malignancy AEs observed. Transient ALT R3x ULN occurred in 3 patients (HD 1 [1.5%], LD 2 [3.1%]) and decreased with continued treatment. Conclusions: Modulation of S1P receptors in patients with moderate to severe UC with RPC1063 1 mg induced clinical remission, clinical response, and mucosal improvement, validating a novel therapeutic approach for the treatment of UC. The positive efficacy and the safety/tolerability results from this study suggest a favorable risk-benefit profile of RPC1063 that supports a Phase 3 UC program.
Volume 81, No. 5S : 2015 GASTROINTESTINAL ENDOSCOPY AB147