Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

Lexicon Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03066830

2016-002826-35 (EudraCT Number)

EFC14835

U1111-1186-2612 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on Hemoglobin A1c (HbA1c) reduction at Week 26 in participant with type 2 diabetes (T2D) who have inadequate glycemic control with a Sulfonylurea alone or in combination with Metformin.

Secondary Objectives:

• To compare Sotagliflozin 400 mg versus placebo based on:
• 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 (mm Hg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Percentage of participants with HbA1c <6.5% and <7.0%.
• To evaluate the safety of Sotagliflozin 400 mg versus placebo throughout the 79-week trial.

Full description

The duration per participants is up to 85 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, and a 2-week post treatment Follow-up period to collect safety information.

Enrollment: 507 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Participants with T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose [documented]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose [documented]) each at a stable dose for at least 12 weeks without a dose adjustment before screening.
• Signed written informed consent.

Exclusion criteria:

• At the time of screening, age <18 years or < legal age of majority, whichever is greater.
• Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening.
• Hemoglobin A1c (HbA1c) <7% or HbA1c >10% via central lab test at screening.
• Fasting plasma glucose (FPG) >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.
• Women of childbearing potential with no effective contraceptive method.
• Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit.
• Previous insulin use >1 month (at any time, aside from treatment of gestational diabetes).
• History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit.
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• History of severe hypoglycemia within 6 months prior to the Screening visit.
• Systolic blood pressure (SBP) >180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg or history of hypertensive emergency.
• Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN).
• Total bilirubin: >1.5 times ULN (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.
• Pregnancy, breastfeeding.
• Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol.

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

---

507 participants in 2 patient groups, including a placebo group

Sotagliflozin 400 mg

Experimental group

Description:

Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Treatment:

Drug: Sotagliflozin (SAR439954)

Placebo

Placebo Comparator group

Description:

Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.

Treatment:

Drug: Placebo

Drug: Sulfonylurea

Drug: Metformin