Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy

Lexicon Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02926937

EFC14833

U1111-1180-6169 (Other Identifier)

2016-001799-31 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise.

Secondary Objectives:

• To compare Sotagliflozin 400 mg versus placebo based on:
• 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 per mercury (mmHg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Proportion of participants with HbA1c <6.5%, <7.0%.
• To compare Sotagliflozin 200 mg versus placebo based on:
• Change from baseline in HbA1c.
• Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.
• Change from baseline in body weight.
• Change from baseline in SBP for all participants.
• To evaluate the safety of Sotagliflozin 400 and 200 mg versus placebo.

Full description

Up to 34 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 26-week double-blind Treatment Period, and a 4-week post-treatment Follow-up visit to collect safety information.

Enrollment: 399 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Participants (male and female) with T2D, who are treated with diet and exercise only during the 12 weeks prior to screening.
• 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 kilogram per meter square (kg/m^2) at Screening.
• Hemoglobin A1c (HbA1c) <7% or >10% via central laboratory test at Screening.
• Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligram 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 contraceptive 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.
• Treated with an antidiabetic pharmacological agent within the 12 weeks prior to the Screening Visit.
• Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes).
• History of 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 millimeter of mercury (mmHg) (systolic) or >100 mmHg (diastolic).
• History of hypertensive 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 that, according to the Investigator, will preclude their safe participation in this study, or will make 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. Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research.
• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
• Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of <30 millimeter per minute (mL/min)/1.73 meter square (m^2)² at screening by the 4 variable Modification of Diet in Renal Disease (MDRD) equation.
• Participant 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.
• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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399 participants in 3 patient groups, including a placebo group

Sotagliflozin 400 mg

Experimental group

Description:

Following a 2-week run-in period, participants were randomized to Sotagliflozin 400 milligrams (mg) administered as two 200 mg tablets, once daily (QD), before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Treatment:

Drug: Sotagliflozin (SAR439954)

Sotagliflozin 200 mg

Experimental group

Description:

Following a 2-week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 Sotagliflozin tablet and 1 matching placebo tablet, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Treatment:

Drug: Placebo

Drug: Sotagliflozin (SAR439954)

Placebo

Placebo Comparator group

Description:

Following a 2-week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Treatment:

Drug: Placebo