Clinical trial NCT03351478: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-11-22
Enrollment: 770
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) % at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥ 130 mmHg
timeFrame: Baseline, Week 12
measure: Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Body Weight at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Sitting SBP at Week 12 for All Participants
timeFrame: Baseline, Week 12
measure: Percentage of Participants With HbA1c <6.5% at Week 26
timeFrame: Week 26
measure: Percentage of Participants With HbA1c <7.0% at Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8408035
state: Alabama
city: Sheffield
country: United States
facility: Investigational Site Number 8408028
state: Alabama
city: Hawaiian Gardens
country: United States
facility: Investigational Site Number 8408047
state: California
city: Spring Valley
country: United States
facility: Investigational Site Number 8408031
state: California
city: Van Nuys
country: United States
facility: Investigational Site Number 8408067
state: California
city: Northglenn
country: United States
facility: Investigational Site Number 8408069
state: Colorado
city: Miami
country: United States
facility: Investigational Site Number 8408009
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8408049
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8408005
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8408040
state: Florida
city: Palmetto Bay
country: United States
facility: Investigational Site Number 8408019
state: Florida
city: Port Charlotte
country: United States
facility: Investigational Site Number 8408064
state: Florida
city: Columbus
country: United States
facility: Investigational Site Number 8408061
state: Georgia
city: Macon
country: United States
facility: Investigational Site Number 8408074
state: Georgia
city: Savannah
country: United States
facility: Investigational Site Number 8408079
state: Georgia
city: Statesboro
country: United States
facility: Investigational Site Number 8408059
state: Georgia
city: Blackfoot
country: United States
facility: Investigational Site Number 8408051
state: Idaho
city: Elgin
country: United States
facility: Investigational Site Number 8408033
state: Illinois
city: New Orleans
country: United States
facility: Investigational Site Number 8408003
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 8408002
state: Maryland
city: Fall River
country: United States
facility: Investigational Site Number 8408044
state: Massachusetts
city: Flint
country: United States
facility: Investigational Site Number 8408008
state: Michigan
city: West Seneca
country: United States
facility: Investigational Site Number 8408027
state: New York
city: Fayetteville
country: United States
facility: Investigational Site Number 8408037
state: North Carolina
city: Greensboro
country: United States
facility: Investigational Site Number 8408053
state: North Carolina
city: Greensboro
country: United States
facility: Investigational Site Number 8408012
state: North Carolina
city: Salisbury
country: United States
facility: Investigational Site Number 8408013
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigational Site Number 8408045
state: Oklahoma
city: Warwick
country: United States
facility: Investigational Site Number 8408068
state: Rhode Island
city: Fort Mill
country: United States
facility: Investigational Site Number 8408060
state: South Carolina
city: Jefferson City
country: United States
facility: Investigational Site Number 8408018
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 8408010
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 8408038
state: Tennessee
city: Brownsville
country: United States
facility: Investigational Site Number 8408072
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8408056
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8408082
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8408052
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408001
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408032
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408016
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408017
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408036
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8408022
state: Texas
city: Katy
country: United States
facility: Investigational Site Number 8408029
state: Texas
city: McAllen
country: United States
facility: Investigational Site Number 8408054
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 8408039
state: Texas
city: Plano
country: United States
facility: Investigational Site Number 8408042
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8408011
state: Texas
city: Schertz
country: United States
facility: Investigational Site Number 8408041
state: Texas
city: Bountiful
country: United States
facility: Investigational Site Number 8408007
state: Utah
city: Holladay
country: United States
facility: Investigational Site Number 8408026
state: Utah
city: Burke
country: United States
facility: Investigational Site Number 8408006
state: Virginia
city: Manassas
country: United States
facility: Investigational Site Number 8408004
state: Virginia
city: Gabrovo
country: Bulgaria
facility: Investigational Site Number 1008011
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1008006
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1008001
city: Ruse
country: Bulgaria
facility: Investigational Site Number 1008005
city: Ruse
country: Bulgaria
facility: Investigational Site Number 1008007
city: Smolyan
country: Bulgaria
facility: Investigational Site Number 1008002
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1008008
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1008012
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 1008003
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 1008010
city: Varna
country: Bulgaria
facility: Investigational Site Number 1008004
city: Brampton
country: Canada
facility: Investigational Site Number 1248001
city: Burlington
country: Canada
facility: Investigational Site Number 1248007
city: Newmarket
country: Canada
facility: Investigational Site Number 1248003
city: Quebec
country: Canada
facility: Investigational Site Number 1248010
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1248009
city: Thornhill
country: Canada
facility: Investigational Site Number 1248002
city: Toronto
country: Canada
facility: Investigational Site Number 1248004
city: Toronto
country: Canada
facility: Investigational Site Number 1248011
city: Vancouver
country: Canada
facility: Investigational Site Number 1248005
city: Victoriaville
country: Canada
facility: Investigational Site Number 1248008
city: Brandys
country: Czechia
facility: Investigational Site Number 2038007
city: Havirov
country: Czechia
facility: Investigational Site Number 2038003
city: Krnov
country: Czechia
facility: Investigational Site Number 2038004
city: Ostrava
country: Czechia
facility: Investigational Site Number 2038011
city: Pardubice
country: Czechia
facility: Investigational Site Number 2038006
city: Plzen
country: Czechia
facility: Investigational Site Number 2038010
city: Prague
country: Czechia
facility: Investigational Site Number 2038005
city: Praha 10 - Uhrineves
country: Czechia
facility: Investigational Site Number 2038001
city: Praha 1
country: Czechia
facility: Investigational Site Number 2038009
city: Praha 2
country: Czechia
facility: Investigational Site Number 2038013
city: Praha 4
country: Czechia
facility: Investigational Site Number 2038002
city: Praha 9
country: Czechia
facility: Investigational Site Number 2038008
city: Corbeil-Essonnes
country: France
facility: Investigational Site Number 2508005
city: La Roche Sur Yon
country: France
facility: Investigational Site Number 2508006
city: La Tronche
country: France
facility: Investigational Site Number 2508007
city: Mulhouse
country: France
facility: Investigational Site Number 2508003
city: Nantes Cedex 1
country: France
facility: Investigational Site Number 2508002
city: Paris
country: France
facility: Investigational Site Number 2508001
city: Saint-Mandé
country: France
facility: Investigational Site Number 2508004
city: Catania
country: Italy
facility: Investigational Site Number 3808010
city: Catania
country: Italy
facility: Investigational Site Number 3808003
city: Chieti
country: Italy
facility: Investigational Site Number 3808002
city: Milano
country: Italy
facility: Investigational Site Number 3808004
city: Milano
country: Italy
facility: Investigational Site Number 3808005
city: Pavia
country: Italy
facility: Investigational Site Number 3808009
city: Roma
country: Italy
facility: Investigational Site Number 3808008
city: Roma
country: Italy
facility: Investigational Site Number 3808001
city: Roma
country: Italy
facility: Investigational Site Number 3808007
city: San Giovanni Rotondo
country: Italy
facility: Investigational Site Number 3808011
city: Siena
country: Italy
facility: Investigational Site Number 3808006
city: Kuldiga
country: Latvia
facility: Investigational Site Number 4288004
city: Limbazi
country: Latvia
facility: Investigational Site Number 4288008
city: Ogre
country: Latvia
facility: Investigational Site Number 4288003
city: Riga
country: Latvia
facility: Investigational Site Number 4288007
city: Riga
country: Latvia
facility: Investigational Site Number 4288001
city: Riga
country: Latvia
facility: Investigational Site Number 4288002
city: Sigulda
country: Latvia
facility: Investigational Site Number 4288006
city: Talsi
country: Latvia
facility: Investigational Site Number 4288005
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4848002
city: Cuernavaca
country: Mexico
facility: Investigational Site Number 4848003
city: Durango, Durango
country: Mexico
facility: Investigational Site Number 4848007
city: Mexico City
country: Mexico
facility: Investigational Site Number 4848011
city: Monterrey
country: Mexico
facility: Investigational Site Number 4848005
city: Monterrey
country: Mexico
facility: Investigational Site Number 4848001
city: Monterrey
country: Mexico
facility: Investigational Site Number 4848012
city: Chelyabinsk
country: Russian Federation
facility: Investigational Site Number 6438008
city: Dzerzhinsky
country: Russian Federation
facility: Investigational Site Number 6438006
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6438009
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 6438010
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6438013
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6438003
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6438002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6438005
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6438001
city: Saratov
country: Russian Federation
facility: Investigational Site Number 6438012
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 6438014
city: Volgograd
country: Russian Federation
facility: Investigational Site Number 6438015
city: Vsevolozhsk
country: Russian Federation
facility: Investigational Site Number 6438007
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 6438011
city: Bardejov
country: Slovakia
facility: Investigational Site Number 7038005
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7038009
city: Kosice
country: Slovakia
facility: Investigational Site Number 7038001
city: Lucenec
country: Slovakia
facility: Investigational Site Number 7038006
city: Nove Zamky
country: Slovakia
facility: Investigational Site Number 7038008
city: Povazska Bystrica
country: Slovakia
facility: Investigational Site Number 7038004
city: Roznava
country: Slovakia
facility: Investigational Site Number 7038002
city: Sabinov
country: Slovakia
facility: Investigational Site Number 7038007
city: Vrutky
country: Slovakia
facility: Investigational Site Number 7038003
city: Barcelona
country: Spain
facility: Investigational Site Number 7248006
city: Córdoba
country: Spain
facility: Investigational Site Number 7248002
city: Malaga Malaga
country: Spain
facility: Investigational Site Number 7248005
city: Santa Coloma De Gramenet
country: Spain
facility: Investigational Site Number 7248010
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 7248009
city: Sevilla
country: Spain
facility: Investigational Site Number 7248004
city: Sevilla
country: Spain
facility: Investigational Site Number 7248008
city: Sevilla
country: Spain
facility: Investigational Site Number 7248001
city: Valencia Valencia
country: Spain
facility: Investigational Site Number 7248003
city: Zaragoza
country: Spain
facility: Investigational Site Number 7248007
city: Darlington
country: United Kingdom
facility: Investigational Site Number 8268008
city: Dundee
country: United Kingdom
facility: Investigational Site Number 8268004
city: Exeter
country: United Kingdom
facility: Investigational Site Number 8268006
city: Hull
country: United Kingdom
facility: Investigational Site Number 8268001
city: Huntingdon
country: United Kingdom
facility: Investigational Site Number 8268002
city: Sheffield
country: United Kingdom
facility: Investigational Site Number 8268007
city: Southampton
country: United Kingdom
facility: Investigational Site Number 8268003
city: Wolverhampton
country: United Kingdom
facility: Investigational Site Number 8268005
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason
role: STUDY_DIRECTOR
References: