Clinical trial NCT03058029: Effect of Gelesis200 on Body Weight in Overweight and Obese Subjects w/o Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Overweight
Diabetes
PreDiabetes
Obesity
Lead sponsor: Gelesis, Inc.
Sponsor class: INDUSTRY
First posted: 2017-02-20
Enrollment: 300
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to one of two groups in parallel for the duration of the study
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Male or female
2. Age ≥22 years and ≤65 years
3. Ambulatory
4. BMI ≥27 kg/M2 and ≤40 kg/M2
5. Non-diabetic subjects, including:

   1. Normoglycemic subjects with FPG \<100 mg/dL \[\<5.6 mmol/L\] at both Screening Visits with HbA1c \<5.7% (\<39 mmol/mol), or
   2. Prediabetic subjects with FPG ≥100 mg/dL and \<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:

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   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 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
6. Ability to follow verbal and written instructions
7. Consent obtained via signed ICF

Exclusion Criteria:

1. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential)
2. 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)
3. History of allergic reaction to CMC, citric acid, sodium stearyl fumarate, maltodextrin, gelatin, or titanium dioxide
4. Participation in a weight loss study within the past six (6) months
5. Administration of GSP2, GSP3, Gelesis100, or Gelesis200 in a previous study
6. Administration of investigational products within one (1) month prior to Screening Visit 1
7. Blood transfusion within three (3) months prior to Screening Visit 1
8. Smoking cessation within six (6) months prior to Screening Visit 1 or considering smoking cessation during the study
9. Anticipated surgical intervention during the study period
10. Known Type 1 Diabetes
11. 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
12. Weight change ≥3% within three (3) months prior to and during the Screening period
13. Supine SBP \>160 mm Hg and/or supine DBP \>95 mm Hg
14. Angina, coronary bypass, or myocardial infarction within six (6) months prior to Screening Visit 1
15. History of swallowing disorders within six (6) months prior to Screening Visit 1
16. Esophageal anatomic abnormalities (e.g., webs, diverticuli, rings)
17. History of gastric or duodenal ulcer within six (6) months prior to Screening Visit 1
18. History of gastroparesis (e.g., chronic nausea, vomiting ≥2 occurrences per week, heartburn, etc.) within six (6) months prior to Screening Visit 1
19. History of gastric bypass or any other gastric surgery
20. History of inflammatory bowel diseases
21. History of intestinal stricture (e.g., Crohn's disease)
22. History of intestinal obstruction or high risk of intestinal obstruction, including suspected small bowel adhesions
23. History of pancreatitis within six (6) months prior to Screening Visit 1
24. History of malabsorption within six (6) months prior to Screening Visit 1
25. Laxative users, except those on stable doses within one (1) month prior to Screening Visit 1
26. History of hepatitis B or C within six (6) months prior to Screening Visit 1
27. History of HIV
28. History of cancer within the past five (5) years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
29. Any other clinically significant disease interfering with the assessments of Gelesis200 (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)
30. Abnormal serum TSH
31. HbA1c \>8.5% (\>69 mmol/mol)
32. Serum LDL cholesterol ≥160 mg/dL (≥4.15 mmol/L)
33. Serum triglycerides ≥350 mg/dL (≥3.96 mmol/L)
34. Positive test for drugs of abuse in the urine
35. Any relevant biochemical abnormality interfering with the assessments of Gelesis200
36. Anti-obesity medications (including herbal preparations) within one (1) month prior to Screening Visit 1
37. Systemic corticosteroids within one (1) month prior to Screening Visit 1
38. Thyroid hormones or preparations within one (1) month prior to Screening Visit 1 \[except stable dose of replacement therapy for at least two (2) months\]
39. TSH suppression therapy for thyroid cancer
40. Estrogen within one (1) month prior to Screening Visit 1 \[except stable dose of replacement therapy or contraceptives for at least one (1) month\]
41. Any other medication known to cause weight loss or weight gain within one (1) month prior to Screening Visit 1
42. Antidiabetic medications within one (1) month prior to Screening Visit 1 \[except stable doses of metformin and DPP-4 inhibitors for at least one (1) month in subjects with Type 2 Diabetes\]
43. Change in medications treating hypertension within one (1) month \[one (1) week for diuretics\] prior to Screening Visit 1
44. Change in medications treating dyslipidemia within one (1) month prior to Screening Visit 1
45. Anticipated requirement for use of prohibited concomitant medications
46. Any other condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to participate in the study

Primary outcomes:
measure: Proportion of subjects with weight loss ≥5.0%
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in body weight
timeFrame: Change from baseline to day 171 (week 25)
Secondary outcomes:
measure: Proportion of subjects with weight loss ≥10.0%
timeFrame: Up to 25 weeks
measure: Proportion of subjects with weight loss ≥10.0%
timeFrame: Up to 25 weeks
measure: Proportion of subjects with weight loss ≥10.0%
timeFrame: Up to 25 weeks
measure: Proportion of subjects with weight loss ≥5.0%
timeFrame: Up to 25 weeks
measure: Proportion of subjects with weight loss ≥5.0%
timeFrame: Up to 25 weeks
measure: Percent change in FSI
timeFrame: Up to 25 weeks
measure: Percent change in insulin AUC during OGTT
timeFrame: Up to 25 weeks
measure: Change in HbA1c
timeFrame: Up to 25 weeks
Other outcomes:
measure: Proportion of subjects with weight loss ≥7.5%
timeFrame: Change from baseline to day 171 (week 25)
measure: Proportion of subjects with weight loss ≥7.5%
timeFrame: Change from baseline to day 171 (week 25)
measure: Proportion of subjects with weight loss ≥7.5%
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in body weight
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in body weight
timeFrame: Change from baseline to day 171 (week 25)
measure: Change in waist circumference
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in estimated excess body weight
timeFrame: Change from baseline to day 171 (week 25)
measure: Change in BMI
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in FSI
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in HOMA-IR and log HOMA-IR
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in QUICKI
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in fasting serum lipids
timeFrame: Change from baseline to day 171 (week 25)
measure: Change in blood pressure
timeFrame: Change from baseline to day 171 (week 25)
measure: Proportion of subjects with weight loss ≥5.0%
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in body weight
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in FSI
timeFrame: Change from baseline to day 171 (week 25)
measure: Percent change in insulin AUC during OGTT
timeFrame: Change from baseline to day 171 (week 25)
measure: Proportion of subjects with weight loss ≥7.5%
timeFrame: Change from baseline to day 171 (week 25)
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Bradenton
country: United States
facility: Meridien Research, Inc - Bradenton
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, P.A.
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research
state: Kansas
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Cincinnati
country: United States
facility: Radiant Research
state: Ohio
city: Greer
country: United States
facility: Mountain View Clinical Research - Greer
state: South Carolina
city: Knoxville
country: United States
facility: Volunteer Research Group and New Orleans Center for Clinical Research - Knoxville
state: Tennessee
city: San Antonio
country: United States
facility: SAMCRC
state: Texas
city: Sugar Land
country: United States
facility: Tarheel Clinical Research, LLC
state: Texas
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
city: Ottawa
country: Canada
facility: University of Ottawa - Institut de Recherche de l'Hospital d'Ottawa (IRHO) (Ottawa Hospital Research Institute (OHRI))
state: Ontario
city: Quebec City
country: Canada
facility: Université Laval
state: Quebec
city: Prague
country: Czechia
facility: Health&Care, s.r.o
city: Frederiksberg
country: Denmark
facility: University of Copenhagen - Department of Nutrition, Exercise and Sports
city: Budapest
country: Hungary
facility: Qualiclinic Kft
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
city: Lodz
country: Poland
facility: NZOZ All - Med Centrum Medyczne Specjalistyczne Gabinety Lekarskie Marcin Ogorek
city: Oswiecim
country: Poland
facility: MEDICOME Sp. z o.o.
city: Poznan
country: Poland
facility: Centrum Zdrowia Metabolicznego Pawel Bogdanski
city: Warszawa
country: Poland
facility: Centrum Badawcze Wspolczesnej Terapii
city: Blackburn
country: United Kingdom
facility: Oakenhurst Medical Practice
city: Chesterfield
country: United Kingdom
facility: Ashgate Medical Practice (Research Office)
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
References: