Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Participants With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy

NCT ID: NCT03332771

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 954 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2019-09-06

Brief Summary

Primary Objective:

To demonstrate the non-inferiority of Sotagliflozin 400 milligrams (mg) compared to Glimepiride on hemoglobin A1c (HbA1c) reduction at Week 52 in participants with Type 2 Diabetes (T2D) who have inadequate glycemic control with metformin.

Secondary Objectives:

To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in body weight, systolic blood pressure (SBP) in participants with baseline SBP ≥130 millimeter of mercury (mmHg), SBP in all participants, and proportion of participants with at least 1 documented symptomatic hypoglycemic event (≤70 milligrams per deciliter [mg/dL]).

• To demonstrate the superiority of Sotagliflozin 400 mg compared to placebo on change in HbA1c, body weight, SBP in participants with baseline SBP ≥130 mmHg, SBP in all participants.
• To demonstrate the superiority of Sotagliflozin 200 mg compared to placebo on change in HbA1c.
• To demonstrate the non-inferiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c.
• To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c.
• To evaluate the safety and tolerability of Sotagliflozin compared to Glimepiride and placebo.

Detailed Description

Up to 58 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks, a 2-week single-blind placebo Run-in phase, a 52-week double-blind Treatment Period, and a 2-week post-treatment Follow-up period to collect safety information.

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Sotagliflozin 400 mg

Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Group Type: EXPERIMENTAL

Sotagliflozin (SAR439954)

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Sotagliflozin 200 mg

Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Group Type: EXPERIMENTAL

Sotagliflozin (SAR439954)

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Glimepiride

Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks.

Group Type: PLACEBO_COMPARATOR

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Interventions

Sotagliflozin (SAR439954)

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Glimepiride

Pharmaceutical form: capsule

Route of administration: oral

Intervention Type: DRUG

Metformin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: capsule

Route of administration: oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants with Type 2 Diabetes (T2D) treated with metformin at a stable dose ≥1500 milligrams per day (mg/day) or maximum tolerated dose (documented) for at least 12 weeks prior to Screening Visit; in case of documented lack of tolerance, metformin dose <1500 mg/day is acceptable, and the dose should be stable for at least 12 weeks prior to Screening Visit.
• Participants has given written informed consent to participate in the study in accordance with local regulations.

Exclusion Criteria

• Age <18 years at the Screening Visit or <legal age of majority, whichever is greater.
• Type 1 diabetes mellitus.
• HbA1c, HbA1c <7.0% or HbA1c >10% at Screening.
• Fasting Plasma Glucose (FPG) >15 millimoles per liter (mmol/L) (>270 milligram per deciliter [mg/dL]) measured by the central laboratory at Screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [>270 mg/dL]) before randomization.
• Body mass index ≤20 or >45 kilogram per meter square (kg/m^2) at Screening.
• Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women.
• Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy (see Appendix A) during the study.
• Previous use of any antidiabetic drug other than Metformin within 12 weeks preceding the Screening Visit.
• Use of a selective Sodium-glucose co-transporter-2 (SGLT2) inhibitor (e.g., Canagliflozin, Dapagliflozin, or Empagliflozin) within 3 months prior to the Screening visit.
• Use of systemic glucocorticoids (excluding topical, or ophthalmic application, intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• Previous insulin use >1 month (at any time, except for treatment of gestational diabetes).
• History of prior gastric surgical procedure, including gastric banding, or inflammatory bowel disease within 3 years prior to the Screening Visit.
• Difficulty swallowing such that the participants cannot take the investigational medicinal product (IMP).
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• Mean of 3 separate blood pressure measurements >180 millimeter of mercury (mmHg) (SBP) or >100 mmHg (DBP).
• History of hypertensive emergency within 12 weeks prior to Screening.
• Participants who have previously been randomized in any clinical trial of Sotagliflozin/LX4211.
• Participants with severe renal disease as defined by an estimated glomerular filtration rate (eGFR) of <30 milliliter per minute per meter square (mL/min/1.73 m^2) at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation (or according to the renal function restrictions of metformin use defined in the local approved label).
• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
• Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN).
• Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome).
• Participants who have taken other investigational drugs within 12 weeks or 5 half-lives from Screening whichever is longer.
• Participants unwilling or unable to perform self-monitoring blood glucose (SMBG), complete the participant diary, or comply with study visits and other study procedures as required per protocol.
• Participants with contraindication to glimepiride as per local labelling.
• Participants with contraindication to metformin as per local labelling.

The above information is not intended to contain all considerations relevant to a Participants 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, MD

Role: STUDY_DIRECTOR

Lexicon Pharmaceuticals, Inc.

Locations

Investigational Site Number 8407040

Birmingham, Alabama, United States

Investigational Site Number 8407048

Birmingham, Alabama, United States

Investigational Site Number 8407035

Little Rock, Arkansas, United States

Investigational Site Number 8407051

Anaheim, California, United States

Investigational Site Number 8407065

Canoga Park, California, United States

Investigational Site Number 8407078

Carmichael, California, United States

Investigational Site Number 8407089

Downey, California, United States

Investigational Site Number 8407011

Gold River, California, United States

Investigational Site Number 8407044

Greenbrae, California, United States

Investigational Site Number 8407006

Huntington Park, California, United States

Investigational Site Number 8407037

Lemon Grove, California, United States

Investigational Site Number 8407100

Lomita, California, United States

Investigational Site Number 8407033

Long Beach, California, United States

Investigational Site Number 8407019

Los Angeles, California, United States

Investigational Site Number 8407098

Northridge, California, United States

Investigational Site Number 8407094

Norwalk, California, United States

Investigational Site Number 8407106

Pomona, California, United States

Investigational Site Number 8407096

Rancho Cucamonga, California, United States

Investigational Site Number 8407036

Sacramento, California, United States

Investigational Site Number 8407084

Tarzana, California, United States

Investigational Site Number 8407034

Upland, California, United States

Investigational Site Number 8407032

Van Nuys, California, United States

Investigational Site Number 8407004

Walnut Creek, California, United States

Investigational Site Number 8407117

Wildomar, California, United States

Investigational Site Number 8407045

Colorado Springs, Colorado, United States

Investigational Site Number 8407074

Bradenton, Florida, United States

Investigational Site Number 8407027

Clearwater, Florida, United States

Investigational Site Number 8407103

Cooper City, Florida, United States

Investigational Site Number 8407021

Coral Gables, Florida, United States

Investigational Site Number 8407062

Lake Worth, Florida, United States

Investigational Site Number 8407121

Ocoee, Florida, United States

Investigational Site Number 8407024

Orlando, Florida, United States

Investigational Site Number 8407038

Palmetto Bay, Florida, United States

Investigational Site Number 8407093

Pembroke Pines, Florida, United States

Investigational Site Number 8407107

Spring Hill, Florida, United States

Investigational Site Number 8407091

Tampa, Florida, United States

Investigational Site Number 8407113

Tampa, Florida, United States

Investigational Site Number 8407092

West Palm Beach, Florida, United States

Investigational Site Number 8407115

Winter Haven, Florida, United States

Investigational Site Number 8407017

Chicago, Illinois, United States

Investigational Site Number 8407018

Elgin, Illinois, United States

Investigational Site Number 8407046

Gurnee, Illinois, United States

Investigational Site Number 8407119

Springfield, Illinois, United States

Investigational Site Number 8407075

Waterloo, Iowa, United States

Investigational Site Number 8407120

West Des Moines, Iowa, United States

Investigational Site Number 8407095

Topeka, Kansas, United States

Investigational Site Number 8407083

Wichita, Kansas, United States

Investigational Site Number 8407043

Lexington, Kentucky, United States

Investigational Site Number 8407087

Lexington, Kentucky, United States

Investigational Site Number 8407060

Lake Charles, Louisiana, United States

Investigational Site Number 8407058

New Orleans, Louisiana, United States

Investigational Site Number 8407009

New Orleans, Louisiana, United States

Investigational Site Number 8407079

Zachary, Louisiana, United States

Investigational Site Number 8407085

Baltimore, Maryland, United States

Investigational Site Number 8407001

Rockville, Maryland, United States

Investigational Site Number 8407069

Troy, Michigan, United States

Investigational Site Number 8407110

Olive Branch, Mississippi, United States

Investigational Site Number 8407054

Bridgeton, Missouri, United States

Investigational Site Number 8407049

Norfolk, Nebraska, United States

Investigational Site Number 8407039

Omaha, Nebraska, United States

Investigational Site Number 8407061

Papillion, Nebraska, United States

Investigational Site Number 8407108

Las Vegas, Nevada, United States

Investigational Site Number 8407050

Albuquerque, New Mexico, United States

Investigational Site Number 8407116

New York, New York, United States

Investigational Site Number 8407086

New York, New York, United States

Investigational Site Number 8407122

New York, New York, United States

Investigational Site Number 8407123

West Seneca, New York, United States

Investigational Site Number 8407020

Greensboro, North Carolina, United States

Investigational Site Number 8407114

Lenoir, North Carolina, United States

Investigational Site Number 8407015

Morehead City, North Carolina, United States

Investigational Site Number 8407030

Salisbury, North Carolina, United States

Investigational Site Number 8407041

Wilmington, North Carolina, United States

Investigational Site Number 8407101

Winston-Salem, North Carolina, United States

Investigational Site Number 8407099

Cincinnati, Ohio, United States

Investigational Site Number 8407081

Lyndhurst, Ohio, United States

Investigational Site Number 8407057

Norman, Oklahoma, United States

Investigational Site Number 8407073

Oklahoma City, Oklahoma, United States

Investigational Site Number 8407068

Eugene, Oregon, United States

Investigational Site Number 8407104

Beaver, Pennsylvania, United States

Investigational Site Number 8407025

Hatboro, Pennsylvania, United States

Investigational Site Number 8407053

Lansdale, Pennsylvania, United States

Investigational Site Number 8407016

Charleston, South Carolina, United States

Investigational Site Number 8407071

Greer, South Carolina, United States

Investigational Site Number 8407022

Mt. Pleasant, South Carolina, United States

Investigational Site Number 8407031

Mt. Pleasant, South Carolina, United States

Investigational Site Number 8407014

Jefferson City, Tennessee, United States

Investigational Site Number 8407002

Knoxville, Tennessee, United States

Investigational Site Number 8407056

Memphis, Tennessee, United States

Investigational Site Number 8407026

Austin, Texas, United States

Investigational Site Number 8407029

Beaumont, Texas, United States

Investigational Site Number 8407070

Carrollton, Texas, United States

Investigational Site Number 8407102

Corpus Christi, Texas, United States

Investigational Site Number 8407023

Dallas, Texas, United States

Investigational Site Number 8407111

Dallas, Texas, United States

Investigational Site Number 8407013

Fort Worth, Texas, United States

Investigational Site Number 8407080

Houston, Texas, United States

Investigational Site Number 8407088

Houston, Texas, United States

Investigational Site Number 8407090

Katy, Texas, United States

Investigational Site Number 8407042

Lampasas, Texas, United States

Investigational Site Number 8407067

Lufkin, Texas, United States

Investigational Site Number 8407118

Lufkin, Texas, United States

Investigational Site Number 8407059

McAllen, Texas, United States

Investigational Site Number 8407012

Mesquite, Texas, United States

Investigational Site Number 8407007

Plano, Texas, United States

Investigational Site Number 8407005

San Antonio, Texas, United States

Investigational Site Number 8407064

San Antonio, Texas, United States

Investigational Site Number 8407010

Schertz, Texas, United States

Investigational Site Number 8407076

Splendora, Texas, United States

Investigational Site Number 8407063

Clinton, Utah, United States

Investigational Site Number 8407055

Holladay, Utah, United States

Investigational Site Number 8407097

Ogden, Utah, United States

Investigational Site Number 8407072

Salt Lake City, Utah, United States

Investigational Site Number 8407124

Manassas, Virginia, United States

Investigational Site Number 8407105

Richmond, Virginia, United States

Investigational Site Number 8407028

Renton, Washington, United States

Investigational Site Number 1007002

Gabrovo, , Bulgaria

Investigational Site Number 1007008

Plovdiv, , Bulgaria

Investigational Site Number 1007003

Plovdiv, , Bulgaria

Investigational Site Number 1007001

Rousse, , Bulgaria

Investigational Site Number 1007004

Smolyan, , Bulgaria

Investigational Site Number 1007009

Sofia, , Bulgaria

Investigational Site Number 1007005

Stara Zagora, , Bulgaria

Investigational Site Number 1007006

Stara Zagora, , Bulgaria

Investigational Site Number 1007007

Varna, , Bulgaria

Investigational Site Number 3487005

Balatonfüred, , Hungary

Investigational Site Number 3487001

Budapest, , Hungary

Investigational Site Number 3487010

Budapest, , Hungary

Investigational Site Number 3487006

Debrecen, , Hungary

Investigational Site Number 3487008

Debrecen, , Hungary

Investigational Site Number 3487002

Kecskemét, , Hungary

Investigational Site Number 3487004

Nyíregyháza, , Hungary

Investigational Site Number 3487007

Nyíregyháza, , Hungary

Investigational Site Number 7037004

Bardejov, , Slovakia

Investigational Site Number 7037008

Bratislava, , Slovakia

Investigational Site Number 7037007

Bratislava, , Slovakia

Investigational Site Number 7037005

Košice, , Slovakia

Investigational Site Number 7037002

Levice, , Slovakia

Investigational Site Number 7037010

Nitra, , Slovakia

Investigational Site Number 7037009

Rožňava, , Slovakia

Investigational Site Number 7037001

Sabinov, , Slovakia

Investigational Site Number 7037003

Trnava, , Slovakia

Investigational Site Number 7037006

Vrútky, , Slovakia

Countries

United States; Bulgaria; Hungary; Slovakia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001801-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1190-7596

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14838

Identifier Type: -

Identifier Source: org_study_id