Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the superiority of sotagliflozin dose 1 versus placebo on hemoglobin A1c (HbA1c) reduction in Chinese patients with type 2 diabetes (T2D) who have inadequate glycemic control on metformin alone or metformin in combination with sulfonylurea. Secondary Objectives: To compare sotagliflozin dose 1 versus placebo for change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT), change in fasting plasma glucose (FPG), and change in body weight. * To compare sotagliflozin dose 2 versus placebo for change in HbA1c, change in 2-hour PPG following a MMTT, change in FPG, and change in body weight. * To compare sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo for change in systolic blood pressure (SBP) for all patients, and change in SBP for patients with baseline SBP ≥130 mmHg. * To evaluate the safety of sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo.
Detailed description
Total study duration is up to 30 weeks, including a screening period consisting of a screening phase of up to 2 weeks and a 2-week single-blind placebo run-in phase, a 24-week double-blind treatment period, and a 2-week post-treatment follow-up visit period to collect safety information.
Interventions
Pharmaceutical form: tablet Route of administration: oral
DRUGplacebo
Pharmaceutical form: tablet Route of administration: oral
DRUGmetformin
Pharmaceutical form: tablet Route of administration: oral
DRUGsulfonylurea
Pharmaceutical form: tablet Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Chinese patients with T2D diagnosed for at least 1 year, who are treated with diet/exercise and: * Metformin alone at a stable dose ( ≥1500 mg/day or maximum tolerated dose \[documented\]) for at least 8 weeks before the screening visit OR * Metformin in combination with sulfonylurea (≥ half maximum-labelled dose or maximum tolerated dose \[documented\]) each at a stable dose for at least 8 weeks before the screening visit. * Signed written informed consent.
Exclusion criteria
* Age \<18 years at the screening visit. * Type 1 diabetes. * Hemoglobin A1c \<7% or \>10.5% measured by the central laboratory at the screening visit. * Fasting plasma glucose \>15 mmol/L (\>270 mg/dL) measured by the central laboratory at the screening visit and confirmed by a repeat test (\>15 mmol/L \[\>270 mg/dL\]) before randomization. * Body mass index (BMI) ≤20 or \>45 kg/m2 at the screening visit. * Women of childbearing potential not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy during the study. * Previous use of any antidiabetic drug other than metformin and sulphonylurea within the 12 weeks prior to the screening visit. * Previous use of any types of insulin for \>1 month within 12 months before screening. * History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the screening visit. * History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar coma within 12 weeks prior to the screening visit. * History of serious hypoglycemia resulting in unconsciousness, seizure or hospitalization within 6 months prior to the screening visit. * Mean of 3 separate blood pressure measurements \>180 mmHg (SBP) or \>100 mmHg (diastolic blood pressure DBP (DBP)). * History of hypertensive emergency within 12 weeks prior to the screening visit. * Patients with severe anemia, severe cardiovascular (CV) (including congestive heart failure New York Heart Association (NYHA) IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients with short life expectancy that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of the normal (ULN) laboratory range. * Total bilirubin \>1.5 times the ULN (except in case of Gilbert's syndrome). * Use of systemic glucocorticoids (excluding topical or ophthalmic application, nasal spray, or inhaled forms) for more than 10 consecutive days within 90 days prior to the screening visit. * Patient who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives prior to the screening visit, whichever is longer. * Use of a selective SGLT2 inhibitor (eg, canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the screening visit. * Pregnant (confirmed by serum pregnancy test at the screening visit) or breastfeeding women. * Patients with severe renal disease as defined by an eGFR of \<30 mL/min/1.73m² at the screening visit, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation. * Patients with contraindication to metformin as per local labelling. * Patients with contraindication to sulfonylurea as per local labelling if the patient is taking metformin with sulfonylurea. * Patient unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol. * Patients unable to consume at least 50% of the standard meal during the MMTT at baseline (Day 1, Visit 3) before randomization. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin A1c (HbA1c) | Baseline to Week 24 | Absolute change from baseline to week 24 in HbA1c (for sotagliflozin dose 1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting plasma glucose (FPG) | Baseline to Week 24 | Absolute change from baseline to week 24 in FPG (for sotagliflozin dose 1 and 2) |
| Change in body weight | Baseline to Week 24 | Absolute change from baseline to week 24 in body weight (for sotagliflozin dose1 and 2) |
| Change in HbA1c | Baseline to Week 24 | Absolute change from baseline to week 24 in HbA1c (for sotagliflozin dose 2) |
| Change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT) | Baseline to Week 24 | Absolute change from baseline to week 24 in 2-hour PPG following a MMTT (for sotagliflozin dose1 and 2) |
| Change in SBP for patients with baseline SBP ≥130 mmHg | Baseline to Week 12 | Absolute change from baseline to week 12 in SBP for patients with baseline SBP ≥130 mmHg (for sotagliflozin dose 1 and 2) |
| Adverse events | Up to Week 24 | Number of patients with adverse events |
| Change in systolic blood pressure (SBP) for all patients | Baseline to Week 12 | Absolute change from baseline to week 12 in SBP for all patients (for sotagliflozin dose 1 and 2) |
Countries
China
Outcome results
None listed