Effect of GSP3 on Body Weight in Overweight and Obese Subjects

• GSP3 (Device): Each capsule of GSP3 (previously Attiva) contains 700 mg of a mixture of two food-grade materials: carboxymethylcellulose that is cross-linked with citric acid.
• Avicel (modified Cellulose) (Dietary supplement): Each capsule of Avicel contains approximately 350 mg of microcrystalline cellulose

Primary outcomes

• Change in Body Weight [Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)]: Change from baseline in kilograms and percent (%) weight

Secondary outcomes

• Body weight responders [12 weeks]: Change from baseline in body weight of at least 5%
• Change in waist circumference [Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)]: Change from baseline in waist circumference (centimeters)
• Change in fat mass [Measured at weeks 0 and 13]: Change in percentage (%) of total mas from baseline in fat- and bone-free fat mass measured by dual energy X-ray absorptiometry (DEXA)
• Change in bone-free fat mass [Measured at weeks 0 and 13]: Change in percentage (%) of total mas from baseline in fat- and bone-free fat mass measured by dual energy X-ray absorptiometry (DEXA)
• Change in appetite (hunger, satiety, and fullness) [Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)]: Assessed by self-administered Visual Analog Scale (VAS)
• Change in food intake [Measured at weeks 0 and 12]: Assessed by 24 hr dietary recall

Other outcomes

• Change in plasma glucose [Measured at baseline and week 13]: Change from baseline in millimoles per liter (mmol/L)
• Change in plasma glucose status (normal, impaired, diabetic) [Measured at weeks 0 and 13]
• Change in serum insulin [Measured at weeks 0 and 13]: Change from baseline in miliunits per liter (mU/L)
• Change in insulin resistance [Measured at weeks 0 and 13]: Change from baseline in homeostatic model assessment of insulin resistance (HOMA-IR)
• Change in glycosylated hemoglobin (HbA1c) [Measured at weeks 0 and 13]: Measured in percentage (%)
• Change in total cholesterol, serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol/HDL ratio, and triglycerides [Measured at weeks 0 and 13]: measured in mg/dL
• Change vital signs: heart rate, supine and standing systolic and diastolic blood pressure (SBP, DBP) [Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)]: Measured in beats per minute (heart rate) or millimeters of mercury (mmHg) for blood pressure
• All adverse events (AE), serious adverse events (SAE), and gastrointestinal symptoms [Measured at weeks 0,1,2,4,6,8,10,12,13, and follow up (week 14)]: Number and % of subjects with AE/SAEs spontaneously reported; gastrointestinal symptoms solicited via questionnaire
• Change in serum sodium [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline in millimoles per liter (mmol/L)
• Change in serum potassium [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum coloride [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum calcium [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum magnesium [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum phosphorus [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum glucose [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in blood urea nitrogen (BUN) [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (mmol/L)
• Change in serum creatinine [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline in micromoles per liter (umol/L)
• Change in serum uric acid [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (umol/L)
• Change in total bilirubin [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (umol/L)
• Change in alanine aminotransferase (ALT) [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline in international units per liter (IU/L)
• Change in aspartate transaminase (AST) [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (IU/L)
• Change in gamma-glutamyl transpeptidase (GGT) [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (IU/L)
• Change in alkaline phosphatase (ALP) [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (IU/L)
• Change in serum total protein [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline in grams per liter (g/L)
• Change in serum albumin [Measured at weeks 0,4,8,12,13 and follow up (week 14)]: Change from baseline (g/L)
• Change in hematocrit [Measured at weeks 0,4,8,12,13 and follow-up (week 14)]: Change from baseline (%)
• Change in hemoglobin [Measured at weeks 0,4,8,12,13 and follow-up (week 14)]: Change from baseline (%)

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Body Mass Index (BMI) ≥ 27 and ≤ 35 (at least 30% overweight and 30% obese subjects)
2. Ability to follow verbal and written instructions
3. Informed Consent Form signed by the subjects

Exclusion Criteria:

1. Pregnancy or lactation
2. Absence of medically approved contraceptive methods in females of childbearing potential (e.g., hysterectomy, non-oral contraceptive medications or intrauterine device combined with a barrier method, two combined barrier methods such as diaphragm and condom or spermicide; bilateral tubal ligation and vasectomy are not acceptable contraceptive methods)
3. History of allergic reaction to carboxymethylcellulose, citric acid, modified cellulose, microcrystalline cellulose, and gelatin
4. Administration of investigational products within 1 month prior to Screening Visit
5. Night-shift workers
6. Subjects who stopped smoking within 6 months prior to Screening Visit or considering smoking cessation during the study
7. Subjects anticipating surgical intervention during the study
8. Known type 1 or type 2 diabetes
9. History of eating disorders including binge eating (except mild binge eater)
10. Weight change > 3 kg within 3 months prior to and during the Screening period
11. Supine systolic blood pressure (SBP) > 150 mm Hg and/or supine diastolic blood pressure (DBP) > 90 mm Hg
12. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
13. History of gastroesophageal reflux disease
14. History of gastric or duodenal ulcer
15. History of gastroparesis
16. History of gastric bypass or any other gastric surgery
17. History of intragastric balloon
18. History of pancreatitis
19. History of hemorrhoids
20. History of malabsorption
21. Laxative users
22. History of hepatitis B or C
23. History of human immunodeficiency virus
24. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
25. Any other clinically significant disease interfering with the assessments of Attiva, according to the Investigator
26. Positive serum or urine pregnancy test(s) in females of childbearing potential
27. Plasma glucose ≥ 126 mg/dL (7.0 mmol/L)
28. Abnormal serum thyrotropin (TSH)
29. Serum triglycerides > 500 mg/dL (5.65 mmol/L)
30. Positive test for drugs in the urine
31. Any relevant biochemical abnormality interfering with the assessments of Attiva, according to the Investigator
32. Anti-obesity medications (including herbal preparations) within 1 month prior to Screening Visit
33. Systemic corticosteroids within 1 month prior to Screening Visit
34. Thyroid hormones or preparations within 1 month prior to Screening Visit (except in subjects on stable dose of replacement therapy for at least 1 month)
35. Any other medication known to cause weight loss or weight gain within 1 month prior to Screening Visit
36. Medications treating hypertension within 1 month prior to Screening Visit
37. Medications treating dyslipidemia within 1 month prior to Screening Visit
38. Anticipated requirement for use of prohibited concomitant medications

• Results publication: Greenway FL, Aronne LJ, Raben A, Astrup A, Apovian CM, Hill JO, Kaplan LM, Fujioka K, Matejkova E, Svacina S, Luzi L, Gnessi L, Navas-Carretero S, Alfredo Martinez J, Still CD, Sannino A, Saponaro C, Demitri C, Urban LE, Leider H, Chiquette E, Ron ES, Zohar Y, Heshmati HM. A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss. Obesity (Silver Spring). 2019 Feb;27(2):205-216. doi: 10.1002/oby.22347. Epub 2018 Nov 13. PMID 30421844

• Hassan Heshmati, MD, Study director, Gelesis, Inc.