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

NCT03351478 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC148672016-001803-22U1111-1190-7607
• Study Type: interventional
• Target: 770
• Locations: 12 countries
• Sites: 160

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥ 130 mmHg

  Baseline, Week 12

• Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26

  Baseline, Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline, Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline, Week 26

• Change From Baseline in Sitting SBP at Week 12 for All Participants

  Baseline, Week 12

Study Arms (3)

Sotagliflozin 400 mg

EXPERIMENTAL

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.

Drug: Sotagliflozin; Drug: Placebo

Empagliflozin 25 mg

ACTIVE COMPARATOR

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.

Drug: Empagliflozin; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Sotagliflozin DRUG

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

Also known as: SAR439954

Sotagliflozin 400 mg

Empagliflozin DRUG

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

Empagliflozin 25 mg

Placebo DRUG

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

Empagliflozin 25 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (160)

Investigational Site Number 8408035

Birmingham, Alabama, 35205, United States

Location

Investigational Site Number 8408028

Sheffield, Alabama, 35660, United States

Location

Investigational Site Number 8408047

Hawaiian Gardens, California, 90716, United States

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Investigational Site Number 8408031

Spring Valley, California, 91978, United States

Location

Investigational Site Number 8408067

Van Nuys, California, 91405, United States

Location

Investigational Site Number 8408069

Northglenn, Colorado, 80234, United States

Location

Investigational Site Number 8408009

Miami, Florida, 33183-4825, United States

Location

Investigational Site Number 8408049

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 8408005

Orlando, Florida, 32810, United States

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Investigational Site Number 8408040

Orlando, Florida, 32825, United States

Location

Investigational Site Number 8408019

Palmetto Bay, Florida, 33157-5503, United States

Location

Investigational Site Number 8408064

Port Charlotte, Florida, 33952, United States

Location

Investigational Site Number 8408061

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 8408074

Macon, Georgia, 31210, United States

Location

Investigational Site Number 8408079

Savannah, Georgia, 31406, United States

Location

Investigational Site Number 8408059

Statesboro, Georgia, 30461-0845, United States

Location

Investigational Site Number 8408051

Blackfoot, Idaho, 83221, United States

Location

Investigational Site Number 8408033

Elgin, Illinois, 60124, United States

Location

Investigational Site Number 8408003

New Orleans, Louisiana, 70124, United States

Location

Investigational Site Number 8408002

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 8408044

Fall River, Massachusetts, 02721-3005, United States

Location

Investigational Site Number 8408008

Flint, Michigan, 48532, United States

Location

Investigational Site Number 8408027

West Seneca, New York, 14224, United States

Location

Investigational Site Number 8408037

Fayetteville, North Carolina, 28314, United States

Location

Investigational Site Number 8408053

Greensboro, North Carolina, 27408-7042, United States

Location

Investigational Site Number 8408012

Greensboro, North Carolina, 27408, United States

Location

Investigational Site Number 8408013

Salisbury, North Carolina, 28144-2742, United States

Location

Investigational Site Number 8408045

Oklahoma City, Oklahoma, 73104-3252, United States

Location

Investigational Site Number 8408068

Warwick, Rhode Island, 02888-3360, United States

Location

Investigational Site Number 8408060

Fort Mill, South Carolina, 29707-4514, United States

Location

Investigational Site Number 8408018

Jefferson City, Tennessee, 37760, United States

Location

Investigational Site Number 8408010

Knoxville, Tennessee, 37912-4707, United States

Location

Investigational Site Number 8408038

Knoxville, Tennessee, 37938, United States

Location

Investigational Site Number 8408072

Brownsville, Texas, 78520-7512, United States

Location

Investigational Site Number 8408056

Dallas, Texas, 75208, United States

Location

Investigational Site Number 8408082

Dallas, Texas, 75230, United States

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Investigational Site Number 8408052

Dallas, Texas, 75231, United States

Location

Investigational Site Number 8408001

Houston, Texas, 77004, United States

Location

Investigational Site Number 8408032

Houston, Texas, 77004, United States

Location

Investigational Site Number 8408016

Houston, Texas, 77040, United States

Location

Investigational Site Number 8408017

Houston, Texas, 77058, United States

Location

Investigational Site Number 8408036

Houston, Texas, 77061, United States

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Investigational Site Number 8408022

Houston, Texas, 77099, United States

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Investigational Site Number 8408029

Katy, Texas, 77450, United States

Location

Investigational Site Number 8408054

McAllen, Texas, 78504, United States

Location

Investigational Site Number 8408039

Mesquite, Texas, 75149, United States

Location

Investigational Site Number 8408042

Plano, Texas, 75024, United States

Location

Investigational Site Number 8408011

San Antonio, Texas, 78229-3818, United States

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Investigational Site Number 8408041

Schertz, Texas, 78154, United States

Location

Investigational Site Number 8408007

Bountiful, Utah, 84010-7717, United States

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Investigational Site Number 8408026

Holladay, Utah, 84117, United States

Location

Investigational Site Number 8408006

Burke, Virginia, 22015, United States

Location

Investigational Site Number 8408004

Manassas, Virginia, 20110, United States

Location

Investigational Site Number 1008011

Gabrovo, 5300, Bulgaria

Location

Investigational Site Number 1008006

Plovdiv, 4000, Bulgaria

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Investigational Site Number 1008001

Plovdiv, 4002, Bulgaria

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Investigational Site Number 1008005

Rousse, 7002, Bulgaria

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Investigational Site Number 1008007

Rousse, 7003, Bulgaria

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Investigational Site Number 1008002

Smolyan, 4700, Bulgaria

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Investigational Site Number 1008008

Sofia, 1606, Bulgaria

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Investigational Site Number 1008012

Sofia, 1632, Bulgaria

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Investigational Site Number 1008003

Stara Zagora, 6000, Bulgaria

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Investigational Site Number 1008010

Stara Zagora, 6000, Bulgaria

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Investigational Site Number 1008004

Varna, 9000, Bulgaria

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Investigational Site Number 1248001

Brampton, L6T 0G1, Canada

Location

Investigational Site Number 1248007

Burlington, L7M 4Y1, Canada

Location

Investigational Site Number 1248003

Newmarket, L3Y 5G8, Canada

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Investigational Site Number 1248010

Québec, G1N 4V3, Canada

Location

Investigational Site Number 1248009

Sherbrooke, J1L 0H8, Canada

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Investigational Site Number 1248002

Thornhill, L4J 1W3, Canada

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Investigational Site Number 1248004

Toronto, M3M 3E5, Canada

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Investigational Site Number 1248011

Toronto, M9W 4L6, Canada

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Investigational Site Number 1248005

Vancouver, V5Y 3W2, Canada

Location

Investigational Site Number 1248008

Victoriaville, G6P 6P6, Canada

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Investigational Site Number 2038007

Brandys, 250 01, Czechia

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Investigational Site Number 2038003

Havířov, 736 01, Czechia

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Investigational Site Number 2038004

Krnov, 794 01, Czechia

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Investigational Site Number 2038011

Ostrava, 710 00, Czechia

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Investigational Site Number 2038006

Pardubice, 530 02, Czechia

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Investigational Site Number 2038010

Pilsen, 363 01, Czechia

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Investigational Site Number 2038009

Prague, 110 00, Czechia

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Investigational Site Number 2038013

Prague, 128 00, Czechia

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Investigational Site Number 2038002

Prague, 149 00, Czechia

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Investigational Site Number 2038005

Prague, 18100, Czechia

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Investigational Site Number 2038008

Prague, 190 14, Czechia

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Investigational Site Number 2038001

Praha 10 - Uhrineves, 104 00, Czechia

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Investigational Site Number 2508005

Corbeil-Essonnes, 91106, France

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Investigational Site Number 2508006

La Roche-sur-Yon, 85925, France

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Investigational Site Number 2508007

La Tronche, 38700, France

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Investigational Site Number 2508003

Mulhouse, 68100, France

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Investigational Site Number 2508002

Nantes, 44093, France

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Investigational Site Number 2508001

Paris, 75018, France

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Investigational Site Number 2508004

Saint-Mandé, 94160, France

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Investigational Site Number 3808010

Catania, 95122, Italy

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Investigational Site Number 3808003

Catania, 95123, Italy

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Investigational Site Number 3808002

Chieti, 66100, Italy

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Investigational Site Number 3808004

Milan, 20122, Italy

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Investigational Site Number 3808005

Milan, 20132, Italy

Location

Investigational Site Number 3808009

Pavia, 27100, Italy

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Investigational Site Number 3808008

Roma, 00133, Italy

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Investigational Site Number 3808001

Roma, 00168, Italy

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Investigational Site Number 3808007

Roma, 161, Italy

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Investigational Site Number 3808011

San Giovanni Rotondo, 71013, Italy

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Investigational Site Number 3808006

Siena, 53100, Italy

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Investigational Site Number 4288004

Kuldīga, 3301, Latvia

Location

Investigational Site Number 4288008

Limbaži, 4000, Latvia

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Investigational Site Number 4288003

Ogre, 5001, Latvia

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Investigational Site Number 4288007

Riga, LV -1021, Latvia

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Investigational Site Number 4288001

Riga, LV-1002, Latvia

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Investigational Site Number 4288002

Riga, LV-1011, Latvia

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Investigational Site Number 4288006

Sigulda, LV-2150, Latvia

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Investigational Site Number 4288005

Talsi, LV-3200, Latvia

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Investigational Site Number 4848002

Chihuahua City, 31200, Mexico

Location

Investigational Site Number 4848003

Cuernavaca, 62250, Mexico

Location

Investigational Site Number 4848007

Durango, Durango, 34080, Mexico

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Investigational Site Number 4848011

Mexico City, 06700, Mexico

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Investigational Site Number 4848005

Monterrey, 07960-6136, Mexico

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Investigational Site Number 4848001

Monterrey, 64020, Mexico

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Investigational Site Number 4848012

Monterrey, 64460, Mexico

Location

Investigational Site Number 6438008

Chelyabinsk, 454047, Russia

Location

Investigational Site Number 6438006

Dzerzhinsky, 140091, Russia

Location

Investigational Site Number 6438009

Kemerovo, 650002, Russia

Location

Investigational Site Number 6438010

Novosibirsk, 630091, Russia

Location

Investigational Site Number 6438013

Saint Petersburg, 190013, Russia

Location

Investigational Site Number 6438003

Saint Petersburg, 192012, Russia

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Investigational Site Number 6438014

Saint Petersburg, 194354, Russia

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Investigational Site Number 6438002

Saint Petersburg, 194358, Russia

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Investigational Site Number 6438005

Saint Petersburg, 195213, Russia

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Investigational Site Number 6438001

Saint Petersburg, 196601, Russia

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Investigational Site Number 6438012

Saratov, 410054, Russia

Location

Investigational Site Number 6438015

Volgograd, 400001, Russia

Location

Investigational Site Number 6438007

Vsevolozhsk, 188643, Russia

Location

Investigational Site Number 6438011

Yaroslavl, 150002, Russia

Location

Investigational Site Number 7038005

Bardejov, 085 01, Slovakia

Location

Investigational Site Number 7038009

Bratislava, 8210, Slovakia

Location

Investigational Site Number 7038001

Košice, 4014, Slovakia

Location

Investigational Site Number 7038006

Lučenec, 984 01, Slovakia

Location

Investigational Site Number 7038008

Nové Zámky, 940 01, Slovakia

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Investigational Site Number 7038004

Považská Bystrica, 1701, Slovakia

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Investigational Site Number 7038002

Rožňava, 048 01, Slovakia

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Investigational Site Number 7038007

Sabinov, 08301, Slovakia

Location

Investigational Site Number 7038003

Vrútky, 038 61, Slovakia

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Investigational Site Number 7248006

Barcelona, 8035, Spain

Location

Investigational Site Number 7248002

Córdoba, 14011, Spain

Location

Investigational Site Number 7248005

Malaga Malaga, 29006, Spain

Location

Investigational Site Number 7248010

Santa Coloma de Gramenet, 08923, Spain

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Investigational Site Number 7248009

Santiago de Compostela, 15706, Spain

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Investigational Site Number 7248004

Seville, 41010, Spain

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Investigational Site Number 7248008

Seville, 41013, Spain

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Investigational Site Number 7248001

Seville, 41071, Spain

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Investigational Site Number 7248003

Valencia, 46014, Spain

Location

Investigational Site Number 7248007

Zaragoza, 50009, Spain

Location

Investigational Site Number 8268008

Darlington, DL3 6HX, United Kingdom

Location

Investigational Site Number 8268004

Dundee, DD1 9SY, United Kingdom

Location

Investigational Site Number 8268006

Exeter, EX2 5DW, United Kingdom

Location

Investigational Site Number 8268001

Hull, HU3 2RW, United Kingdom

Location

Investigational Site Number 8268002

Huntingdon, PE29 6NT, United Kingdom

Location

Investigational Site Number 8268007

Sheffield, S5 7AU, United Kingdom

Location

Investigational Site Number 8268003

Southampton, SO30 3JB, United Kingdom

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Investigational Site Number 8268005

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Affairs
• Organization: Lexicon Pharmaceuticals, Inc

medical-information@lexpharma.com

(510) 338-6064

Study Officials

• Suman Wason

  Lexicon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: November 22, 2017
• Study Start: November 27, 2017
• Primary Completion: May 16, 2019
• Study Completion: May 16, 2019
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (8); SL (9); BU (11); CA (10); RU (14); ME (7); ES (10); US (53); CZ (12); LA (8); IT (11); FR (7)