Effect of Gelesis200 on Body Weight in Overweight and Obese Subjects With Prediabetes and With and Without Type 2 Diabetes

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

Inclusion Criteria:

Male or female ambulatory subjects Age ≥22 years and ≤65 years Body Mass Index (BMI) ≥27
and ≤40 kilogram (kg)/meter (M)2

Non-diabetic subjects,including:

1. Normoglycemic subjects with FPG ≥90 milligram (mg)/deciliter (dL) and <100 mg/dL
[≥5.0millimole (mmol)/liter (L) and <5.6 mmol/L] at both Screening Visits with HbA1c
<5.7% (<39 mmol/mol), or

2. Prediabetic subjects with FPG≥100 mg/dL and <126mg/dL [≥5.6 millimole (mmol)/liter (L)
and <7.0mmol/L] at both Screening Visits with HbA1c ≤6.4%[≤46 mmol/mole (mol)][if only
one (1)value is within this range, the other value should not be ≥126mg/dL
(≥7.0mmol/L) and HbA1c should be ≥5.7% (≥39 mmol/mol) and ≤6.4%(≤46 mmol/mol)]

or Diabetic subjects, including:

1. 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

2. Drug-treated subjects with metformin and/or dipeptidyl peptidase-4 (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

Fasting serum insulin <24 microunit (µU)/milliliter (mL)at both Screening Visits in
normoglycemic subjects 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[exempli gratia (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 another single method from above]
History of allergic reaction to carboxymethylcellulose(CMC), citric acid, maltodextrin,
gelatin, ortitanium dioxide Participation in a weight loss study within the past six (6)
months Administration of Prototype 2 (GSP2), Prototype 3 (GSP3), Gelesis100,or Gelesis200
in a previous study Administration of investigational products within one(1) month prior to
Screening Visit Blood transfusion within three (3) months prior to Screening Visit Smoking
cessation within six(6) months prior to Screening Visit 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 for mild binge
eating)or emesis ≥2/week from any cause Weight change >3% within three(3) months prior to
and during the Screening period Supine systolic blood pressure (SBP) >160 millimeters of
mercury (mmHg)and/or supine diastolic blood pressure(DBP) >95mmHg Angina, coronary bypass,
or myocardial infarction within six(6)months prior to Screening Visit History of swallowing
disorders Esophageal anatomic abnormalities (e.g., webs, diverticuli, rings)•History of
gastroesophageal reflux disease History of gastric or duodenal ulcer History of
gastroparesis(e.g., chronic nausea, vomiting≥2 occurrences per week, heartburn, etc.)
History of gastric bypass or any other gastric surgery History of small bowel resection
(except if related to appendectomy) 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 abdominal radiation treatment History of
pancreatitis within the past 12 months History of malabsorption Laxative users, except
those on stable doses within one (1) month prior to Screening Visit History of hepatitis B
or C History of human immunodeficiency virus(HIV) History of cancer within the past five(5)
years (except adequately-treated localized basal cell skin cancer or in situuterine
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 thyroid-stimulating hormone(TSH) HbA1c >8.5% (>69 mmol/mol)
Serum low-density lipoprotein (LDL) cholesterol≥160mg/dL (≥4.15mmol/L) Serum triglycerides
≥350 mg/dL (≥3.96mmol/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
Systemic corticosteroids within one (1) month prior to Screening Visit Thyroid hormones or
preparations within one (1) month prior to Screening Visit [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 [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 Antidiabetic
medications within one (1) month prior to Screening Visit [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 prior to Screening Visit Change in
medications treating dyslipidemia within one (1) month prior to Screening Visit 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