Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin (SOTA-EMPA)

Lexicon Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Sotagliflozin; Drug: Empagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03351478

U1111-1190-7607 (Other Identifier)

EFC14867

2016-001803-22 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is 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 on a DPP4(i) with or without metformin.

Enrollment: 770 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Participants with Type 2 Diabetes on Dipeptidyl peptidase-4 inhibitors(DPP4(i)) with or without metformin at a stable dose for at least 12 weeks prior to Screening Visit. Metformin dose will be ≥1500 mg per day (or maximum tolerated dose [documented]). DPP4(i) dose must be the appropriate dose as per local label.
• Signed written informed consent.

Exclusion criteria:

• Body mass index (BMI) ≤20 kg/m^2 or >45 kg/m^2 at Screening.
• Use of any antidiabetic drug other than DPP4 inhibitors and metformin within 12 weeks preceding the Screening Visit.
• Participants who have previously participated in any clinical trial of sotagliflozin/LX4211.
• Use of a selective sodium-glucose co-transporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the screening visit.
• Participants with severe anemia, severe cardiovascular disease (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with a short life expectancy that, according to Investigator, will preclude their safe participation in this study, or will make the implementation of the protocol or interpretation of the study results difficult.
• Current diagnosis of chronic hepatitis and/or other clinically active liver disease requiring treatment.
• Participants with contraindication to empagliflozin as per local labelling.
• Participants with contraindication to metformin as per local labelling.
• Hemoglobin A1c <7.0% or >11.0% at Screening (central laboratory).
• Fasting plasma glucose >270 mg/dL (>15.0 mmol/L) measured by the central laboratory at Screening (Visit 1), and confirmed by a repeat test (>270 mg/dL [>15.0 mmol/L]) before Randomization.
• Previous use of any type of insulin for >1 month (except for treatment of gestational diabetes).
• Pregnant (confirmed by serum pregnancy test at Screening) or breast-feeding women.
• Women of childbearing potential not willing to use highly effective method(s) of birth control during the study treatment period and follow-up period, or who are unwilling or unable to be tested for pregnancy during the study.
• Mean of 3 separate blood pressure (BP) measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).
• History of the hypertensive crisis resulting in emergency medical care within 12 weeks prior to Screening Visit.
• Lower extremity complications (such as skin ulcers, infection, osteomyelitis, and gangrene) identified during the Screening period, and still requiring treatment at Randomization.
• Laboratory findings with the central laboratory tests at Visit 1:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range (ULN);
• Total bilirubin >1.5 times the ULN (except in case of Gilbert's syndrome);
• Neutrophils <1 500/mm^3 (or according to ethnic group) and/or platelets <100 000/mm^3;
• Amylase and/or lipase >3 times the ULN;
• Participants with renal impairment as defined by the estimated glomerular filtration rate (eGFR) criterion that precludes initiation of empagliflozin as per the approved local label (eg, <45 mL/min/1.73 m^2 in US; <60 mL/min/1.73 m^2 in EU).
• Secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
• If the participant is on hypertensive medications, the antihypertensive has been changed in the 8 weeks prior to Screening (new drug or new dose).

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

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770 participants in 3 patient groups, including a placebo group

Sotagliflozin 400 mg

Experimental group

Description:

Following a 2-week run-in period, sotagliflozin 400 mg (milligrams) administered as two 200 mg tablets and one placebo capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day for up to 26 weeks.

Treatment:

Drug: Placebo

Drug: Sotagliflozin

Drug: Placebo

Empagliflozin 25 mg

Active Comparator group

Description:

Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks.

Treatment:

Drug: Placebo

Drug: Empagliflozin

Drug: Placebo

Placebo

Placebo Comparator group

Description:

Following a 2-week run-in period, placebo was given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day for up to 26 weeks.

Treatment:

Drug: Placebo

Drug: Placebo