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

NCT ID: NCT03351478

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 770 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-27
• Study Completion Date: 2019-05-16

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sotagliflozin 400 mg

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.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.

Placebo

Intervention Type: DRUG

Placebo was administered as one capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day.

Empagliflozin 25 mg

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.

Group Type: ACTIVE_COMPARATOR

Empagliflozin

Intervention Type: DRUG

Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day.

Placebo

Intervention Type: DRUG

Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.

Interventions

Sotagliflozin

Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.

Intervention Type: DRUG

Empagliflozin

Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day.

Intervention Type: DRUG

Placebo

Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.

Intervention Type: DRUG

Placebo

Placebo was administered as one capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day.

Intervention Type: DRUG

Other Intervention Names

SAR439954

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Lexicon Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suman Wason

Role: STUDY_DIRECTOR

Lexicon Pharmaceuticals, Inc.

Locations

Investigational Site Number 8408035

Birmingham, Alabama, United States

Investigational Site Number 8408028

Sheffield, Alabama, United States

Investigational Site Number 8408047

Hawaiian Gardens, California, United States

Investigational Site Number 8408031

Spring Valley, California, United States

Investigational Site Number 8408067

Van Nuys, California, United States

Investigational Site Number 8408069

Northglenn, Colorado, United States

Investigational Site Number 8408009

Miami, Florida, United States

Investigational Site Number 8408049

Ocoee, Florida, United States

Investigational Site Number 8408005

Orlando, Florida, United States

Investigational Site Number 8408040

Orlando, Florida, United States

Investigational Site Number 8408019

Palmetto Bay, Florida, United States

Investigational Site Number 8408064

Port Charlotte, Florida, United States

Investigational Site Number 8408061

Columbus, Georgia, United States

Investigational Site Number 8408074

Macon, Georgia, United States

Investigational Site Number 8408079

Savannah, Georgia, United States

Investigational Site Number 8408059

Statesboro, Georgia, United States

Investigational Site Number 8408051

Blackfoot, Idaho, United States

Investigational Site Number 8408033

Elgin, Illinois, United States

Investigational Site Number 8408003

New Orleans, Louisiana, United States

Investigational Site Number 8408002

Rockville, Maryland, United States

Investigational Site Number 8408044

Fall River, Massachusetts, United States

Investigational Site Number 8408008

Flint, Michigan, United States

Investigational Site Number 8408027

West Seneca, New York, United States

Investigational Site Number 8408037

Fayetteville, North Carolina, United States

Investigational Site Number 8408053

Greensboro, North Carolina, United States

Investigational Site Number 8408012

Greensboro, North Carolina, United States

Investigational Site Number 8408013

Salisbury, North Carolina, United States

Investigational Site Number 8408045

Oklahoma City, Oklahoma, United States

Investigational Site Number 8408068

Warwick, Rhode Island, United States

Investigational Site Number 8408060

Fort Mill, South Carolina, United States

Investigational Site Number 8408018

Jefferson City, Tennessee, United States

Investigational Site Number 8408010

Knoxville, Tennessee, United States

Investigational Site Number 8408038

Knoxville, Tennessee, United States

Investigational Site Number 8408072

Brownsville, Texas, United States

Investigational Site Number 8408056

Dallas, Texas, United States

Investigational Site Number 8408082

Dallas, Texas, United States

Investigational Site Number 8408052

Dallas, Texas, United States

Investigational Site Number 8408001

Houston, Texas, United States

Investigational Site Number 8408032

Houston, Texas, United States

Investigational Site Number 8408016

Houston, Texas, United States

Investigational Site Number 8408017

Houston, Texas, United States

Investigational Site Number 8408036

Houston, Texas, United States

Investigational Site Number 8408022

Houston, Texas, United States

Investigational Site Number 8408029

Katy, Texas, United States

Investigational Site Number 8408054

McAllen, Texas, United States

Investigational Site Number 8408039

Mesquite, Texas, United States

Investigational Site Number 8408042

Plano, Texas, United States

Investigational Site Number 8408011

San Antonio, Texas, United States

Investigational Site Number 8408041

Schertz, Texas, United States

Investigational Site Number 8408007

Bountiful, Utah, United States

Investigational Site Number 8408026

Holladay, Utah, United States

Investigational Site Number 8408006

Burke, Virginia, United States

Investigational Site Number 8408004

Manassas, Virginia, United States

Investigational Site Number 1008011

Gabrovo, , Bulgaria

Investigational Site Number 1008006

Plovdiv, , Bulgaria

Investigational Site Number 1008001

Plovdiv, , Bulgaria

Investigational Site Number 1008005

Rousse, , Bulgaria

Investigational Site Number 1008007

Rousse, , Bulgaria

Investigational Site Number 1008002

Smolyan, , Bulgaria

Investigational Site Number 1008008

Sofia, , Bulgaria

Investigational Site Number 1008012

Sofia, , Bulgaria

Investigational Site Number 1008003

Stara Zagora, , Bulgaria

Investigational Site Number 1008010

Stara Zagora, , Bulgaria

Investigational Site Number 1008004

Varna, , Bulgaria

Investigational Site Number 1248001

Brampton, , Canada

Investigational Site Number 1248007

Burlington, , Canada

Investigational Site Number 1248003

Newmarket, , Canada

Investigational Site Number 1248010

Québec, , Canada

Investigational Site Number 1248009

Sherbrooke, , Canada

Investigational Site Number 1248002

Thornhill, , Canada

Investigational Site Number 1248004

Toronto, , Canada

Investigational Site Number 1248011

Toronto, , Canada

Investigational Site Number 1248005

Vancouver, , Canada

Investigational Site Number 1248008

Victoriaville, , Canada

Investigational Site Number 2038007

Brandys, , Czechia

Investigational Site Number 2038003

Havířov, , Czechia

Investigational Site Number 2038004

Krnov, , Czechia

Investigational Site Number 2038011

Ostrava, , Czechia

Investigational Site Number 2038006

Pardubice, , Czechia

Investigational Site Number 2038010

Pilsen, , Czechia

Investigational Site Number 2038009

Prague, , Czechia

Investigational Site Number 2038013

Prague, , Czechia

Investigational Site Number 2038002

Prague, , Czechia

Investigational Site Number 2038005

Prague, , Czechia

Investigational Site Number 2038008

Prague, , Czechia

Investigational Site Number 2038001

Praha 10 - Uhrineves, , Czechia

Investigational Site Number 2508005

Corbeil-Essonnes, , France

Investigational Site Number 2508006

La Roche-sur-Yon, , France

Investigational Site Number 2508007

La Tronche, , France

Investigational Site Number 2508003

Mulhouse, , France

Investigational Site Number 2508002

Nantes, , France

Investigational Site Number 2508001

Paris, , France

Investigational Site Number 2508004

Saint-Mandé, , France

Investigational Site Number 3808010

Catania, , Italy

Investigational Site Number 3808003

Catania, , Italy

Investigational Site Number 3808002

Chieti, , Italy

Investigational Site Number 3808004

Milan, , Italy

Investigational Site Number 3808005

Milan, , Italy

Investigational Site Number 3808009

Pavia, , Italy

Investigational Site Number 3808008

Roma, , Italy

Investigational Site Number 3808001

Roma, , Italy

Investigational Site Number 3808007

Roma, , Italy

Investigational Site Number 3808011

San Giovanni Rotondo, , Italy

Investigational Site Number 3808006

Siena, , Italy

Investigational Site Number 4288004

Kuldīga, , Latvia

Investigational Site Number 4288008

Limbaži, , Latvia

Investigational Site Number 4288003

Ogre, , Latvia

Investigational Site Number 4288007

Riga, , Latvia

Investigational Site Number 4288001

Riga, , Latvia

Investigational Site Number 4288002

Riga, , Latvia

Investigational Site Number 4288006

Sigulda, , Latvia

Investigational Site Number 4288005

Talsi, , Latvia

Investigational Site Number 4848002

Chihuahua City, , Mexico

Investigational Site Number 4848003

Cuernavaca, , Mexico

Investigational Site Number 4848007

Durango, Durango, , Mexico

Investigational Site Number 4848011

Mexico City, , Mexico

Investigational Site Number 4848005

Monterrey, , Mexico

Investigational Site Number 4848001

Monterrey, , Mexico

Investigational Site Number 4848012

Monterrey, , Mexico

Investigational Site Number 6438008

Chelyabinsk, , Russia

Investigational Site Number 6438006

Dzerzhinsky, , Russia

Investigational Site Number 6438009

Kemerovo, , Russia

Investigational Site Number 6438010

Novosibirsk, , Russia

Investigational Site Number 6438013

Saint Petersburg, , Russia

Investigational Site Number 6438003

Saint Petersburg, , Russia

Investigational Site Number 6438014

Saint Petersburg, , Russia

Investigational Site Number 6438002

Saint Petersburg, , Russia

Investigational Site Number 6438005

Saint Petersburg, , Russia

Investigational Site Number 6438001

Saint Petersburg, , Russia

Investigational Site Number 6438012

Saratov, , Russia

Investigational Site Number 6438015

Volgograd, , Russia

Investigational Site Number 6438007

Vsevolozhsk, , Russia

Investigational Site Number 6438011

Yaroslavl, , Russia

Investigational Site Number 7038005

Bardejov, , Slovakia

Investigational Site Number 7038009

Bratislava, , Slovakia

Investigational Site Number 7038001

Košice, , Slovakia

Investigational Site Number 7038006

Lučenec, , Slovakia

Investigational Site Number 7038008

Nové Zámky, , Slovakia

Investigational Site Number 7038004

Považská Bystrica, , Slovakia

Investigational Site Number 7038002

Rožňava, , Slovakia

Investigational Site Number 7038007

Sabinov, , Slovakia

Investigational Site Number 7038003

Vrútky, , Slovakia

Investigational Site Number 7248006

Barcelona, , Spain

Investigational Site Number 7248002

Córdoba, , Spain

Investigational Site Number 7248005

Malaga Malaga, , Spain

Investigational Site Number 7248010

Santa Coloma de Gramenet, , Spain

Investigational Site Number 7248009

Santiago de Compostela, , Spain

Investigational Site Number 7248004

Seville, , Spain

Investigational Site Number 7248008

Seville, , Spain

Investigational Site Number 7248001

Seville, , Spain

Investigational Site Number 7248003

Valencia, , Spain

Investigational Site Number 7248007

Zaragoza, , Spain

Investigational Site Number 8268008

Darlington, , United Kingdom

Investigational Site Number 8268004

Dundee, , United Kingdom

Investigational Site Number 8268006

Exeter, , United Kingdom

Investigational Site Number 8268001

Hull, , United Kingdom

Investigational Site Number 8268002

Huntingdon, , United Kingdom

Investigational Site Number 8268007

Sheffield, , United Kingdom

Investigational Site Number 8268003

Southampton, , United Kingdom

Investigational Site Number 8268005

Wolverhampton, , United Kingdom

Countries

United States; Bulgaria; Canada; Czechia; France; Italy; Latvia; Mexico; Russia; Slovakia; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001803-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1190-7607

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14867

Identifier Type: -

Identifier Source: org_study_id