Effect of Gelesis200 on Body Weight in Overweight and Obese Subjects w/o Type 2 Diabetes

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Assessing the Effect of Gelesis200 on Body Weight in Overweight and Obese Subjects without or with Type 2 Diabetes

Detailed Description
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Multicenter, two-cohort, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose, adaptive (Two Phases). In the first Phase of the adaptive design, unblinded interim analyses were conducted on 57 subjects and used to adjust the design for the second Phase. The first Phase was completed under protocol Version 1.0. Data used in the unblinded interim analyses of the first Phase will not be included in the second Phase (protocol Version 2.0 and subsequent protocol versions) analyses. The study will evaluate the safety, tolerability and efficacy of Gelesis200 as a superabsorbent hydrogel for weight loss in treated diabetic subjects, untreated diabetic subjects, and prediabetic subjects (Cohort 1). The study will evaluate separately the safety, tolerability and efficacy of Gelesis200 for weight loss in normoglycemic subjects (Cohort 2).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Assessing the Effect of Gelesis200 on Body Weight in Overweight and Obese Subjects Without or With Type 2 Diabetes

Conditions
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Overweight, Diabetes, PreDiabetes, Obesity

Intervention / Treatment
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* Device: Gelesis200
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age ≥22 years and ≤65 years Ambulatory BMI ≥27 kg/M2 and ≤40 kg/M2 Non-diabetic subjects, including: Normoglycemic subjects with FPG <100 mg/dL [<5.6 mmol/L] at both Screening Visits with HbA1c <5.7% (<39 mmol/mol), or Prediabetic subjects with FPG ≥100 mg/dL and <126 mg/dL (≥5.6 mmol/L and ≤7.0 mmol/L) at both Screening Visits with HbA1c ≤6.4% (≤46 mmol/mol) [if only one (1) value is within this range, the other value should not be ≥126 mg/dL (≥7.0 mmol/L) and HbA1c should be ≥5.7% (≥39 mmol/mol) and ≤6.4% (≤46 mmol/mol)]; or Diabetic subjects, including: Untreated subjects with FPG ≤200 mg/dL (≤11.2 mmol/L) at both Screening Visits and either FPG ≥126 mg/dL (≥7.0 mmol/L) at both Screening Visits or FPG <126 mg/dL (<7.0 mmol/L) at one (1) or both Screening Visits with HbA1c ≥6.5% (≥48 mmol/mol), or Drug-treated subjects with metformin and/or DPP-4 inhibitors with FPG ≥70 mg/dL and ≤270 mg/dL (≥3.9 mmol/L and ≤15.1 mmol/L) at both Screening Visits Ability to follow verbal and written instructions Consent obtained via signed ICF Exclusion Criteria: Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) Absence of medically approved contraception in females of childbearing potential (e.g., hysterectomy, oral contraceptive medications, intrauterine device combined with a barrier method, two (2) combined barrier methods such as diaphragm and condom or spermicide, or condom and spermicide; bilateral tubal ligation and vasectomy are acceptable contraceptive methods when combined with a single method above) History of allergic reaction to CMC, citric acid, sodium stearyl fumarate, maltodextrin, gelatin, or titanium dioxide Participation in a weight loss study within the past six (6) months Administration of GSP2, GSP3, Gelesis100, or Gelesis200 in a previous study Administration of investigational products within one (1) month prior to Screening Visit 1 Blood transfusion within three (3) months prior to Screening Visit 1 Smoking cessation within six (6) months prior to Screening Visit 1 or considering smoking cessation during the study Anticipated surgical intervention during the study period Known Type 1 Diabetes History of eating disorders including binge eating (except mild binge eating) or emesis ≥2/week from any cause within six (6) months prior to Screening Visit 1 Weight change ≥3% within three (3) months prior to and during the Screening period Supine SBP >160 mm Hg and/or supine DBP >95 mm Hg Angina, coronary bypass, or myocardial infarction within six (6) months prior to Screening Visit 1 History of swallowing disorders within six (6) months prior to Screening Visit 1 Esophageal anatomic abnormalities (e.g., webs, diverticuli, rings) History of gastric or duodenal ulcer within six (6) months prior to Screening Visit 1 History of gastroparesis (e.g., chronic nausea, vomiting ≥2 occurrences per week, heartburn, etc.) within six (6) months prior to Screening Visit 1 History of gastric bypass or any other gastric surgery History of inflammatory bowel diseases History of intestinal stricture (e.g., Crohn's disease) History of intestinal obstruction or high risk of intestinal obstruction, including suspected small bowel adhesions History of pancreatitis within six (6) months prior to Screening Visit 1 History of malabsorption within six (6) months prior to Screening Visit 1 Laxative users, except those on stable doses within one (1) month prior to Screening Visit 1 History of hepatitis B or C within six (6) months prior to Screening Visit 1 History of HIV History of cancer within the past five (5) years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer) Any other clinically significant disease interfering with the assessments of Gelesis200 (e.g., disease requiring corrective treatment, potentially leading to study discontinuation) Abnormal serum TSH HbA1c >8.5% (>69 mmol/mol) Serum LDL cholesterol ≥160 mg/dL (≥4.15 mmol/L) Serum triglycerides ≥350 mg/dL (≥3.96 mmol/L) Positive test for drugs of abuse in the urine Any relevant biochemical abnormality interfering with the assessments of Gelesis200 Anti-obesity medications (including herbal preparations) within one (1) month prior to Screening Visit 1 Systemic corticosteroids within one (1) month prior to Screening Visit 1 Thyroid hormones or preparations within one (1) month prior to Screening Visit 1 [except stable dose of replacement therapy for at least two (2) months] TSH suppression therapy for thyroid cancer Estrogen within one (1) month prior to Screening Visit 1 [except stable dose of replacement therapy or contraceptives for at least one (1) month] Any other medication known to cause weight loss or weight gain within one (1) month prior to Screening Visit 1 Antidiabetic medications within one (1) month prior to Screening Visit 1 [except stable doses of metformin and DPP-4 inhibitors for at least one (1) month in subjects with Type 2 Diabetes] Change in medications treating hypertension within one (1) month [one (1) week for diuretics] prior to Screening Visit 1 Change in medications treating dyslipidemia within one (1) month prior to Screening Visit 1 Anticipated requirement for use of prohibited concomitant medications Any other condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to participate in the study

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to one of two groups in parallel for the duration of the study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gelesis200<br>Gelesis200: Three (3) Gelesis200 capsules (2.10 gram (g)) two (2) times per day (id est (i.e.), lunch and dinner) | Device: Gelesis200<br>* Subject would take Gelesis200 capsules 2 times per day.<br>|
| Placebo Comparator: Placebo<br>Placebo: Three (3) placebo capsules two (2) times per day (i.e., lunch and dinner) | Device: Placebo<br>* Subject would take placebo capsules 2 times per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with weight loss ≥5.0% | In treated diabetic subjects, untreated diabetic subjects, and pre-diabetic subjects (Cohort 1) | Change from baseline to day 171 (week 25) | 
| Percent change in body weight | In treated diabetic subjects, untreated diabetic subjects, and pre-diabetic subjects (Cohort 1) | Change from baseline to day 171 (week 25) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with weight loss ≥10.0% | In treated diabetic subjects, untreated diabetic subjects, and pre-diabetic subjects (Cohort 1) | Up to 25 weeks | 
| Proportion of subjects with weight loss ≥10.0% | Treated diabetics (subgroup of Cohort 1) | Up to 25 weeks | 
| Proportion of subjects with weight loss ≥10.0% | Pre-diabetics and untreated diabetics (subgroup of Cohort 1) | Up to 25 weeks | 
| Proportion of subjects with weight loss ≥5.0% | Treated diabetic subjects (subgroup of Cohort 1) | Up to 25 weeks | 
| Proportion of subjects with weight loss ≥5.0% | Pre-diabetics and untreated diabetics (subgroup of Cohort 1) | Up to 25 weeks | 
| Percent change in FSI | Pre-diabetics and untreated diabetics (subgroup of Cohort 1) | Up to 25 weeks | 
| Percent change in insulin AUC during OGTT | Pre-diabetic subjects (subgroup of Cohort 1) | Up to 25 weeks | 
| Change in HbA1c | Diabetic subjects with HbA1c ≥7.5% (≥58 mmol/mol) at baseline (subgroup of Cohort 1) | Up to 25 weeks |