Obesity, Overweight
Conditions
Brief summary
This study will asses the decrease in body weight after repeated administration of Gelesis100 in overweight and obese subjects with and without Type 2 Diabetes.
Detailed description
To asses the decrease in body weight after repeated administration of Gelesis100 in overweight and obese subjects with and without Type 2 Diabetes.
Interventions
DEVICEGelesis100
DEVICEplacebo
Sponsors
Gelesis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 22 to 65 years of age, inclusive * Signed Informed Consent Form * BMI 27 to 40, inclusive (BMI of \<30 should have at least one comorbidity) * Fasting plasma glucose 90mg/dL to 145 mg/dL, inclusive; non-diabetic normoglycemic (fasting glucose 90 mg/dL to 100 mg/dL, inclusive); non-diabetic impaired fasting glucose 100mg/dL to 126 mg/dL; and diabetic: untreated (126 mg/dL to 145 mg/dL, inclusive) and metformin-treated (metformin dose 1500mg/DL and less, fasting glucose less than 145 mg/dL, inclusive)
Exclusion criteria
* Pregnancy or lactation * Absence of medically approved contraceptive methods in females of childbearing potential * History of allergic reaction to modified cellulose, citric acid, sodium stearyl fumarate, raw cane sugar, gelatin, and titanium oxide * Administration of investigational products within 1 month prior to Screening Visit * Subjects who stopped smoking within 6 months prior to Screening Visit or considering smoking cessation during the study * Subjects anticipating surgical intervention during the study * Known Type 1 diabetes * History of eating disorders * Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit * History of: swallowing disorders, esophogeal anatomic abnormalities, gastroesophageal reflux disease, gastric or duodenal ulcer, gastroparesis (chronic nausea, vomiting, heartburn...), gastric bypass or other gastric surgery, intestinal obstruction or at high risk of including suspected small bowel adhesion, pancreatitis, malabsorption, history of bowel resection (except if related to appendectomy), history of abdominal radiation treatment * Laxative users * History of: HIV, hepatitis B or C; cancer within the past 5 years * Abnormal serum thyroid-stimulating hormone (TSH) * Positive urine drug test * Anti-obesity medication within 1 month prior to Screening Visit (except stable doses of metformin, no more than 1500 mg/day, for at leaset 1 month in subjects with type 2 diabetes) * Systemic corticosteroids within 1 month prior to Screening Visit * Thyroid hormones or preparations within 1 month prior to Screening Visit * Estrogen within 1 month prior to Screening Visit * Any other medication known to cause weight loss or weight gain within 1 month prior to Screening Visit * TSH suppression therapy for thyroid cancer * medications requiring mandatory administration with meal (lunch or dinner), except metformin * Other medication or product used for chronic diseases if their impaired gastrointestinal absorption can cause safety issues * Change in medications treating hypertension and/or dyslipidemia within 1 month prior to Screening Visit (including change in dose) * Anticipated requirement for use of prohibited concomitant medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Co-Primary Outcome: Percentage of Subjects Who Achieve Body Weight Loss ≥ 5% | Baseline to Day 171 | Percentage of participants who achieve a body weight loss ≥ 5% from Baseline to Day 171 is presented. |
| Co-Primary Outcome: Percent Change in Body Weight | Baseline to Day 171 | Percent change in body weight from Baseline to Day 171 is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Baseline to Day 171 | Normal plasma glucose status is defined FPG ≤ 100mg/dL. Impaired plasma glucose status is defined as FPG ≥100mg/dL and \<126mg/dL. Diabetic plasma glucose status was defined as FPG \>126mg/dL. |
| Percent Change in Plasma Glucose | Baseline to Day 171 | Percent change in Plasma Glucose in subjects with impaired glucose and T2D at baseline. Impaired plasma glucose is defined as FPG≥100mg/dL and FPG\<126mg/dL. |
| Change in Hemoglobin HbA1c in Subjects With Type 2 Diabetes at Baseline | Baseline to Day 171 | To assess the decrease in HbA1c after repeated administration of Gelesis 100 over a period of 168 days in overweight and obese people with type 2 diabetes, The glycosylated hemoglobin was measured in mmol/mol. |
| Change in Body Mass Index (BMI) | Baseline to Day 171 | The BMI was calculated using height (in cm) and weight (in kg) according to the following formula: BMI (kg/m2((superscript 1)) = Weight (kg)/\[Height (cm)/100\]2(superscript2). |
| Percent Body Weight Change in Subjects With Impaired Plasma Glucose Status at Baseline | Baseline to Day 171 | Impaired plasma glucose status is defined as Fasting Plasma Glucose (FPG) ≥100mg/dL and \<126mg/dL at baseline measurement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assess Safety and Tolerability of Administration of Gelesis100 | Baseline to Day 197 | Adverse Events (AEs), Physical Examinations, Vital Signs, Laboratory Tests |
Countries
Canada, Czechia, Denmark, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gelesis100 Gelesis100 twice daily
Gelesis100 | 223 |
| Placebo Matching placebo twice daily
placebo | 213 |
| Total | 436 |
Baseline characteristics
| Characteristic | Gelesis100 | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 223 Participants | 436 Participants | 213 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 27 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 212 Participants | 409 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants | 50 Participants | 24 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 189 Participants | 369 Participants | 180 Participants |
| Region of Enrollment Europe | 126 participants | 245 participants | 119 participants |
| Region of Enrollment United States | 97 participants | 191 participants | 94 participants |
| Sex: Female, Male Female | 125 Participants | 245 Participants | 120 Participants |
| Sex: Female, Male Male | 98 Participants | 191 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 223 | 0 / 211 |
| other Total, other adverse events | 159 / 223 | 149 / 211 |
| serious Total, serious adverse events | 0 / 223 | 1 / 211 |
Outcome results
Primary
Co-Primary Outcome: Percentage of Subjects Who Achieve Body Weight Loss ≥ 5%
Percentage of participants who achieve a body weight loss ≥ 5% from Baseline to Day 171 is presented.
Time frame: Baseline to Day 171
Population: Overall Number of Participants Analyzed is equal to the intention to treat population (all randomized subjects).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gelesis100 | Co-Primary Outcome: Percentage of Subjects Who Achieve Body Weight Loss ≥ 5% | 58.6 percentage of participants |
| Placebo | Co-Primary Outcome: Percentage of Subjects Who Achieve Body Weight Loss ≥ 5% | 42.2 percentage of participants |
Comparison: H0: π (Gelesis100)\< 0.35p-value: <0.0001Binomial Proportion Test
Comparison: OR-trt refers to the odds ratio of being a body weight responder for Gelesis100 vs. Placebo.~H0: OR-trt= 1.p-value: 0.000895% CI: [1.34, 3.01]Regression, Logistic
Primary
Co-Primary Outcome: Percent Change in Body Weight
Percent change in body weight from Baseline to Day 171 is presented.
Time frame: Baseline to Day 171
Population: Overall number of patients analyzed is equal to the intention to treat population (all randomized subjects).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gelesis100 | Co-Primary Outcome: Percent Change in Body Weight | -6.41 percentage change in body weight | Standard Deviation 5.79 |
| Placebo | Co-Primary Outcome: Percent Change in Body Weight | -4.39 percentage change in body weight | Standard Deviation 5.52 |
Comparison: Simple Superiority, H0: μ (Placebo) -μ (Gelesis100) = 0p-value: 0.000795% CI: [-3.24, -0.9]ANCOVA
Comparison: Super-Superiority (\>3% difference), H0: μ(Placebo)-μ(Gelesis100) \< 3%p-value: 0.1193ANCOVA
Secondary
Change in Body Mass Index (BMI)
The BMI was calculated using height (in cm) and weight (in kg) according to the following formula: BMI (kg/m2((superscript 1)) = Weight (kg)/\[Height (cm)/100\]2(superscript2).
Time frame: Baseline to Day 171
Population: Overall number of patients analyzed is equal to the number of all participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gelesis100 | Change in Body Mass Index (BMI) | -2.12 kg/m^2 | Standard Deviation 1.92 |
| Placebo | Change in Body Mass Index (BMI) | -1.51 kg/m^2 | Standard Deviation 1.9 |
Secondary
Change in Hemoglobin HbA1c in Subjects With Type 2 Diabetes at Baseline
To assess the decrease in HbA1c after repeated administration of Gelesis 100 over a period of 168 days in overweight and obese people with type 2 diabetes, The glycosylated hemoglobin was measured in mmol/mol.
Time frame: Baseline to Day 171
Population: Overall number of patients analyzed is equal to the number of all participants with type 2 diabetes at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gelesis100 | Change in Hemoglobin HbA1c in Subjects With Type 2 Diabetes at Baseline | -0.64 mmol/mol | Standard Deviation 5.07 |
| Placebo | Change in Hemoglobin HbA1c in Subjects With Type 2 Diabetes at Baseline | -3.06 mmol/mol | Standard Deviation 4.18 |
Secondary
Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline.
Normal plasma glucose status is defined FPG ≤ 100mg/dL. Impaired plasma glucose status is defined as FPG ≥100mg/dL and \<126mg/dL. Diabetic plasma glucose status was defined as FPG \>126mg/dL.
Time frame: Baseline to Day 171
Population: Overall Number of Participants Analyzed is equal to the number of participants with impaired fasting glucose at Baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gelesis100 | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Normal | 23 participants |
| Gelesis100 | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Impaired (Pre-diabetic) | 35 participants |
| Gelesis100 | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Diabetic | 1 participants |
| Placebo | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Normal | 19 participants |
| Placebo | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Impaired (Pre-diabetic) | 34 participants |
| Placebo | Change in Plasma Glucose Status (Normal, Impaired, Diabetic) in Subjects With Impaired Plasma Glucose Status at Baseline. | Diabetic | 5 participants |
Secondary
Percent Body Weight Change in Subjects With Impaired Plasma Glucose Status at Baseline
Impaired plasma glucose status is defined as Fasting Plasma Glucose (FPG) ≥100mg/dL and \<126mg/dL at baseline measurement.
Time frame: Baseline to Day 171
Population: Overall Number of Participants Analyzed is equal to the number of participants with impaired fasting glucose at Baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gelesis100 | Percent Body Weight Change in Subjects With Impaired Plasma Glucose Status at Baseline | -6.46 percentage change in body weight | Standard Deviation 6.28 |
| Placebo | Percent Body Weight Change in Subjects With Impaired Plasma Glucose Status at Baseline | -5.54 percentage change in body weight | Standard Deviation 6.08 |
Secondary
Percent Change in Plasma Glucose
Percent change in Plasma Glucose in subjects with impaired glucose and T2D at baseline. Impaired plasma glucose is defined as FPG≥100mg/dL and FPG\<126mg/dL.
Time frame: Baseline to Day 171
Population: Overall Number of Participants Analyzed is equal to the number of participants with impaired fasting glucose at Baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gelesis100 | Percent Change in Plasma Glucose | -2.39 percentage of change in plasma glucose | Standard Deviation 20.55 |
| Placebo | Percent Change in Plasma Glucose | -1.95 percentage of change in plasma glucose | Standard Deviation 14.61 |
Other Pre-specified
Assess Safety and Tolerability of Administration of Gelesis100
Adverse Events (AEs), Physical Examinations, Vital Signs, Laboratory Tests
Time frame: Baseline to Day 197