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

Type 2 Diabetes Mellitus Clinical Trial

— SOTA-EMPA  

Official title:

A 26-week Randomized, Double-blind, Controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Empagliflozin, and Placebo in Participants With Type 2 Diabetes Who Have Inadequate Glycemic Control on Dipeptidyl Peptidase 4 Inhibitor (DPP4(i)) With or Without Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03351478
• Other study ID #: EFC14867
• Secondary ID: 2016-001803-22U1
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2017
• Est. completion date: May 16, 2019

Study information

• Verified date: April 2021
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 770
• Est. completion date: May 16, 2019
• Est. primary completion date: May 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sotagliflozin
Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.
• Empagliflozin
Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day.
• Placebo
Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.
• Placebo
Placebo was administered as one capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day.

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 1008011	Gabrovo
Bulgaria	Investigational Site Number 1008001	Plovdiv
Bulgaria	Investigational Site Number 1008006	Plovdiv
Bulgaria	Investigational Site Number 1008005	Ruse
Bulgaria	Investigational Site Number 1008007	Ruse
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
Canada	Investigational Site Number 1248001	Brampton
Canada	Investigational Site Number 1248007	Burlington
Canada	Investigational Site Number 1248003	Newmarket
Canada	Investigational Site Number 1248010	Quebec
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
Czechia	Investigational Site Number 2038007	Brandys
Czechia	Investigational Site Number 2038003	Havirov
Czechia	Investigational Site Number 2038004	Krnov
Czechia	Investigational Site Number 2038011	Ostrava
Czechia	Investigational Site Number 2038006	Pardubice
Czechia	Investigational Site Number 2038010	Plzen
Czechia	Investigational Site Number 2038005	Prague
Czechia	Investigational Site Number 2038009	Praha 1
Czechia	Investigational Site Number 2038001	Praha 10 - Uhrineves
Czechia	Investigational Site Number 2038013	Praha 2
Czechia	Investigational Site Number 2038002	Praha 4
Czechia	Investigational Site Number 2038008	Praha 9
France	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 Cedex 1
France	Investigational Site Number 2508001	Paris
France	Investigational Site Number 2508004	Saint-Mandé
Italy	Investigational Site Number 3808003	Catania
Italy	Investigational Site Number 3808010	Catania
Italy	Investigational Site Number 3808002	Chieti
Italy	Investigational Site Number 3808004	Milano
Italy	Investigational Site Number 3808005	Milano
Italy	Investigational Site Number 3808009	Pavia
Italy	Investigational Site Number 3808001	Roma
Italy	Investigational Site Number 3808007	Roma
Italy	Investigational Site Number 3808008	Roma
Italy	Investigational Site Number 3808011	San Giovanni Rotondo
Italy	Investigational Site Number 3808006	Siena
Latvia	Investigational Site Number 4288004	Kuldiga
Latvia	Investigational Site Number 4288008	Limbazi
Latvia	Investigational Site Number 4288003	Ogre
Latvia	Investigational Site Number 4288001	Riga
Latvia	Investigational Site Number 4288002	Riga
Latvia	Investigational Site Number 4288007	Riga
Latvia	Investigational Site Number 4288006	Sigulda
Latvia	Investigational Site Number 4288005	Talsi
Mexico	Investigational Site Number 4848002	Chihuahua
Mexico	Investigational Site Number 4848003	Cuernavaca
Mexico	Investigational Site Number 4848007	Durango, Durango
Mexico	Investigational Site Number 4848011	Mexico City
Mexico	Investigational Site Number 4848001	Monterrey
Mexico	Investigational Site Number 4848005	Monterrey
Mexico	Investigational Site Number 4848012	Monterrey
Russian Federation	Investigational Site Number 6438008	Chelyabinsk
Russian Federation	Investigational Site Number 6438006	Dzerzhinsky
Russian Federation	Investigational Site Number 6438009	Kemerovo
Russian Federation	Investigational Site Number 6438010	Novosibirsk
Russian Federation	Investigational Site Number 6438001	Saint-Petersburg
Russian Federation	Investigational Site Number 6438002	Saint-Petersburg
Russian Federation	Investigational Site Number 6438003	Saint-Petersburg
Russian Federation	Investigational Site Number 6438005	Saint-Petersburg
Russian Federation	Investigational Site Number 6438013	Saint-Petersburg
Russian Federation	Investigational Site Number 6438012	Saratov
Russian Federation	Investigational Site Number 6438014	St. Petersburg
Russian Federation	Investigational Site Number 6438015	Volgograd
Russian Federation	Investigational Site Number 6438007	Vsevolozhsk
Russian Federation	Investigational Site Number 6438011	Yaroslavl
Slovakia	Investigational Site Number 7038005	Bardejov
Slovakia	Investigational Site Number 7038009	Bratislava
Slovakia	Investigational Site Number 7038001	Kosice
Slovakia	Investigational Site Number 7038006	Lucenec
Slovakia	Investigational Site Number 7038008	Nove Zamky
Slovakia	Investigational Site Number 7038004	Povazska Bystrica
Slovakia	Investigational Site Number 7038002	Roznava
Slovakia	Investigational Site Number 7038007	Sabinov
Slovakia	Investigational Site Number 7038003	Vrutky
Spain	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 7248001	Sevilla
Spain	Investigational Site Number 7248004	Sevilla
Spain	Investigational Site Number 7248008	Sevilla
Spain	Investigational Site Number 7248003	Valencia Valencia
Spain	Investigational Site Number 7248007	Zaragoza
United Kingdom	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 States	Investigational Site Number 8408035	Birmingham	Alabama
United States	Investigational Site Number 8408051	Blackfoot	Idaho
United States	Investigational Site Number 8408007	Bountiful	Utah
United States	Investigational Site Number 8408072	Brownsville	Texas
United States	Investigational Site Number 8408006	Burke	Virginia
United States	Investigational Site Number 8408061	Columbus	Georgia
United States	Investigational Site Number 8408052	Dallas	Texas
United States	Investigational Site Number 8408056	Dallas	Texas
United States	Investigational Site Number 8408082	Dallas	Texas
United States	Investigational Site Number 8408033	Elgin	Illinois
United States	Investigational Site Number 8408044	Fall River	Massachusetts
United States	Investigational Site Number 8408037	Fayetteville	North Carolina
United States	Investigational Site Number 8408008	Flint	Michigan
United States	Investigational Site Number 8408060	Fort Mill	South Carolina
United States	Investigational Site Number 8408012	Greensboro	North Carolina
United States	Investigational Site Number 8408053	Greensboro	North Carolina
United States	Investigational Site Number 8408047	Hawaiian Gardens	California
United States	Investigational Site Number 8408026	Holladay	Utah
United States	Investigational Site Number 8408001	Houston	Texas
United States	Investigational Site Number 8408016	Houston	Texas
United States	Investigational Site Number 8408017	Houston	Texas
United States	Investigational Site Number 8408022	Houston	Texas
United States	Investigational Site Number 8408032	Houston	Texas
United States	Investigational Site Number 8408036	Houston	Texas
United States	Investigational Site Number 8408018	Jefferson City	Tennessee
United States	Investigational Site Number 8408029	Katy	Texas
United States	Investigational Site Number 8408010	Knoxville	Tennessee
United States	Investigational Site Number 8408038	Knoxville	Tennessee
United States	Investigational Site Number 8408074	Macon	Georgia
United States	Investigational Site Number 8408004	Manassas	Virginia
United States	Investigational Site Number 8408054	McAllen	Texas
United States	Investigational Site Number 8408039	Mesquite	Texas
United States	Investigational Site Number 8408009	Miami	Florida
United States	Investigational Site Number 8408003	New Orleans	Louisiana
United States	Investigational Site Number 8408069	Northglenn	Colorado
United States	Investigational Site Number 8408049	Ocoee	Florida
United States	Investigational Site Number 8408045	Oklahoma City	Oklahoma
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 8408042	Plano	Texas
United States	Investigational Site Number 8408064	Port Charlotte	Florida
United States	Investigational Site Number 8408002	Rockville	Maryland
United States	Investigational Site Number 8408013	Salisbury	North Carolina
United States	Investigational Site Number 8408011	San Antonio	Texas
United States	Investigational Site Number 8408079	Savannah	Georgia
United States	Investigational Site Number 8408041	Schertz	Texas
United States	Investigational Site Number 8408028	Sheffield	Alabama
United States	Investigational Site Number 8408031	Spring Valley	California
United States	Investigational Site Number 8408059	Statesboro	Georgia
United States	Investigational Site Number 8408067	Van Nuys	California
United States	Investigational Site Number 8408068	Warwick	Rhode Island
United States	Investigational Site Number 8408027	West Seneca	New York

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  France,  Italy,  Latvia,  Mexico,  Russian Federation,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) % at Week 26	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline, Week 26
Secondary	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP = 130 mmHg	An ANCOVA model was used for the analysis.	Baseline, Week 12
Secondary	Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26	An ANCOVA model was used for the analysis.	Baseline, Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model was used for the analysis.	Baseline, Week 26
Secondary	Change From Baseline in Body Weight at Week 26	An ANCOVA model was used for the analysis.	Baseline, Week 26
Secondary	Change From Baseline in Sitting SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline, Week 12
Secondary	Percentage of Participants With HbA1c <6.5% at Week 26		Week 26
Secondary	Percentage of Participants With HbA1c <7.0% at Week 26		Week 26