Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin

Lexicon Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Metformin; Drug: Sotagliflozin (SAR439954)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02926950

EFC14834

U1111-1181-6145 (Other Identifier)

2016-001800-49 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To demonstrate the superiority of Sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control with metformin.

Secondary Objectives:

• To compare Sotagliflozin versus placebo for.
• Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.
• Change from baseline in fasting plasma glucose (FPG).
• Change from Baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter of mercury (mmHg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Proportion of participants with HbA1c <6.5% and <7.0%.
• To evaluate the safety of Sotagliflozin versus placebo.

Full description

The duration of the study period is up to 87 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks and a 2 week single blind Run-in phase, a 26 week double-blind Core Treatment Period, a 53-week double-blind Extension Period, a 4 week post treatment Follow-up period to collect safety information.

Enrollment: 518 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Participants with Type 2 Diabetes currently treated with diet and exercise and on metformin at a stable dose ≥1500 milligrams per day (mg/day) for at least 12 weeks. However, participants on metformin at a dose <1500 mg/day at the time of enrollment (stable dose for at least 12 weeks before enrollment) may be eligible for screening if documentation of lack of tolerance of a metformin dose ≥1500 mg/day can be provided.
• Signed written informed consent.

Exclusion criteria:

• Age <18 years at Screening or < legal age of majority, whichever is greater.
• Type 1 diabetes mellitus.
• Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening
• Hemoglobin A1c <7% or >10% via central laboratory test at screening.
• Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligrams per deciliter [mg/dL]) measured by the central laboratory at screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [270 mg/dL]) before randomization.
• Women of childbearing potential not willing to use highly effective method(s) of birth control or who are unwilling or unable to be tested for pregnancy during the study.
• Treated with an antidiabetic pharmacological regimen other than metformin ≥1500 mg per day (or maximum tolerated dose) within the 12 weeks preceding the Screening Visit.
• Previous use of any types of insulin for >1 month (at any time, aside from pregnancy for treatment of gestational diabetes).
• History of prior gastric surgical procedure, including gastric banding, within 3 years before the Screening Visit.
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic blood pressure [DBP]).
• History of hypertensive urgency or emergency within 12 weeks prior to Screening.
• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association [NYHA] IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with short life expectancy making implementation of the protocol or interpretation of the study results difficult.
• Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range.
• Total bilirubin: >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).
• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from screening or randomization, whichever is longer.
• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
• Participants is unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the participants diary, or comply with study visits and other study procedures as required per protocol.
• Contraindication to metformin as per local labelling.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

518 participants in 2 patient groups, including a placebo group

Sotagliflozin 400 mg + Metformin

Experimental group

Description:

Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.

Treatment:

Drug: Metformin

Drug: Sotagliflozin (SAR439954)

Placebo + Metformin

Placebo Comparator group

Description:

Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.

Treatment:

Drug: Placebo

Drug: Metformin