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

Type 2 Diabetes Mellitus Clinical Trial

— SOTA-GLIM  

Official title:

A 52-week Randomized, Double-blind, Double-dummy, Active and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Glimepiride or Placebo Added to Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03332771
• Other study ID #: EFC14838
• Secondary ID: 2016-001801-17U1
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2017
• Est. completion date: September 6, 2019

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 954
• Est. completion date: September 6, 2019
• Est. primary completion date: August 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sotagliflozin (SAR439954)
Pharmaceutical form: tablet Route of administration: oral
• Glimepiride
Pharmaceutical form: capsule Route of administration: oral
• Metformin
Pharmaceutical form: tablet Route of administration: oral
• Placebo
Pharmaceutical form: tablet Route of administration: oral
• Placebo
Pharmaceutical form: capsule Route of administration: oral

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 1007002	Gabrovo
Bulgaria	Investigational Site Number 1007003	Plovdiv
Bulgaria	Investigational Site Number 1007008	Plovdiv
Bulgaria	Investigational Site Number 1007001	Ruse
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
Hungary	Investigational Site Number 3487005	Balatonfured
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	Kecskemet
Hungary	Investigational Site Number 3487007	Nyiregyhaza
Hungary	Investigational Site Number 3487004	Nyíregyháza
Slovakia	Investigational Site Number 7037004	Bardejov
Slovakia	Investigational Site Number 7037007	Bratislava
Slovakia	Investigational Site Number 7037008	Bratislava
Slovakia	Investigational Site Number 7037005	Kosice
Slovakia	Investigational Site Number 7037002	Levice
Slovakia	Investigational Site Number 7037010	Nitra
Slovakia	Investigational Site Number 7037009	Roznava
Slovakia	Investigational Site Number 7037001	Sabinov
Slovakia	Investigational Site Number 7037003	Trnava
Slovakia	Investigational Site Number 7037006	Vrutky
United States	Investigational Site Number 8407050	Albuquerque	New Mexico
United States	Investigational Site Number 8407051	Anaheim	California
United States	Investigational Site Number 8407026	Austin	Texas
United States	Investigational Site Number 8407085	Baltimore	Maryland
United States	Investigational Site Number 8407029	Beaumont	Texas
United States	Investigational Site Number 8407104	Beaver	Pennsylvania
United States	Investigational Site Number 8407040	Birmingham	Alabama
United States	Investigational Site Number 8407048	Birmingham	Alabama
United States	Investigational Site Number 8407074	Bradenton	Florida
United States	Investigational Site Number 8407054	Bridgeton	Missouri
United States	Investigational Site Number 8407065	Canoga Park	California
United States	Investigational Site Number 8407078	Carmichael	California
United States	Investigational Site Number 8407070	Carrollton	Texas
United States	Investigational Site Number 8407016	Charleston	South Carolina
United States	Investigational Site Number 8407017	Chicago	Illinois
United States	Investigational Site Number 8407099	Cincinnati	Ohio
United States	Investigational Site Number 8407027	Clearwater	Florida
United States	Investigational Site Number 8407063	Clinton	Utah
United States	Investigational Site Number 8407045	Colorado Springs	Colorado
United States	Investigational Site Number 8407103	Cooper City	Florida
United States	Investigational Site Number 8407021	Coral Gables	Florida
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 8407089	Downey	California
United States	Investigational Site Number 8407018	Elgin	Illinois
United States	Investigational Site Number 8407068	Eugene	Oregon
United States	Investigational Site Number 8407013	Fort Worth	Texas
United States	Investigational Site Number 8407011	Gold River	California
United States	Investigational Site Number 8407044	Greenbrae	California
United States	Investigational Site Number 8407020	Greensboro	North Carolina
United States	Investigational Site Number 8407071	Greer	South Carolina
United States	Investigational Site Number 8407046	Gurnee	Illinois
United States	Investigational Site Number 8407025	Hatboro	Pennsylvania
United States	Investigational Site Number 8407055	Holladay	Utah
United States	Investigational Site Number 8407080	Houston	Texas
United States	Investigational Site Number 8407088	Houston	Texas
United States	Investigational Site Number 8407006	Huntington Park	California
United States	Investigational Site Number 8407014	Jefferson City	Tennessee
United States	Investigational Site Number 8407090	Katy	Texas
United States	Investigational Site Number 8407002	Knoxville	Tennessee
United States	Investigational Site Number 8407060	Lake Charles	Louisiana
United States	Investigational Site Number 8407062	Lake Worth	Florida
United States	Investigational Site Number 8407042	Lampasas	Texas
United States	Investigational Site Number 8407053	Lansdale	Pennsylvania
United States	Investigational Site Number 8407108	Las Vegas	Nevada
United States	Investigational Site Number 8407037	Lemon Grove	California
United States	Investigational Site Number 8407114	Lenoir	North Carolina
United States	Investigational Site Number 8407043	Lexington	Kentucky
United States	Investigational Site Number 8407087	Lexington	Kentucky
United States	Investigational Site Number 8407035	Little Rock	Arkansas
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 8407067	Lufkin	Texas
United States	Investigational Site Number 8407118	Lufkin	Texas
United States	Investigational Site Number 8407081	Lyndhurst	Ohio
United States	Investigational Site Number 8407124	Manassas	Virginia
United States	Investigational Site Number 8407059	McAllen	Texas
United States	Investigational Site Number 8407056	Memphis	Tennessee
United States	Investigational Site Number 8407012	Mesquite	Texas
United States	Investigational Site Number 8407015	Morehead City	North Carolina
United States	Investigational Site Number 8407022	Mount Pleasant	South Carolina
United States	Investigational Site Number 8407031	Mount Pleasant	South Carolina
United States	Investigational Site Number 8407009	New Orleans	Louisiana
United States	Investigational Site Number 8407058	New Orleans	Louisiana
United States	Investigational Site Number 8407086	New York	New York
United States	Investigational Site Number 8407116	New York	New York
United States	Investigational Site Number 8407122	New York	New York
United States	Investigational Site Number 8407049	Norfolk	Nebraska
United States	Investigational Site Number 8407057	Norman	Oklahoma
United States	Investigational Site Number 8407098	Northridge	California
United States	Investigational Site Number 8407094	Norwalk	California
United States	Investigational Site Number 8407121	Ocoee	Florida
United States	Investigational Site Number 8407097	Ogden	Utah
United States	Investigational Site Number 8407073	Oklahoma City	Oklahoma
United States	Investigational Site Number 8407110	Olive Branch	Mississippi
United States	Investigational Site Number 8407039	Omaha	Nebraska
United States	Investigational Site Number 8407024	Orlando	Florida
United States	Investigational Site Number 8407038	Palmetto Bay	Florida
United States	Investigational Site Number 8407061	Papillion	Nebraska
United States	Investigational Site Number 8407093	Pembroke Pines	Florida
United States	Investigational Site Number 8407007	Plano	Texas
United States	Investigational Site Number 8407106	Pomona	California
United States	Investigational Site Number 8407096	Rancho Cucamonga	California
United States	Investigational Site Number 8407028	Renton	Washington
United States	Investigational Site Number 8407105	Richmond	Virginia
United States	Investigational Site Number 8407001	Rockville	Maryland
United States	Investigational Site Number 8407036	Sacramento	California
United States	Investigational Site Number 8407030	Salisbury	North Carolina
United States	Investigational Site Number 8407072	Salt Lake City	Utah
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 8407107	Spring Hill	Florida
United States	Investigational Site Number 8407119	Springfield	Illinois
United States	Investigational Site Number 8407091	Tampa	Florida
United States	Investigational Site Number 8407113	Tampa	Florida
United States	Investigational Site Number 8407084	Tarzana	California
United States	Investigational Site Number 8407095	Topeka	Kansas
United States	Investigational Site Number 8407069	Troy	Michigan
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 8407075	Waterloo	Iowa
United States	Investigational Site Number 8407120	West Des Moines	Iowa
United States	Investigational Site Number 8407092	West Palm Beach	Florida
United States	Investigational Site Number 8407123	West Seneca	New York
United States	Investigational Site Number 8407083	Wichita	Kansas
United States	Investigational Site Number 8407117	Wildomar	California
United States	Investigational Site Number 8407041	Wilmington	North Carolina
United States	Investigational Site Number 8407101	Winston-Salem	North Carolina
United States	Investigational Site Number 8407115	Winter Haven	Florida
United States	Investigational Site Number 8407079	Zachary	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Hungary,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hypoglycemic Events	Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose = 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose = 70 mg/dL].	Up to Week 52
Primary	Change From Baseline in Hemoglobin A1c at Week 52	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline, Week 52
Secondary	Change From Baseline in Hemoglobin A1c at Week 26	An ANCOVA model was used for the analysis.	Baseline, Week 26
Secondary	Change From Baseline in Body Weight at Week 26 and 52	An ANCOVA model was used for the analysis.	Baseline, Week 26, Week 52
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP =130 mmHg at Week 12	An ANCOVA model was used for the analysis.	Baseline, Week 12
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12	An ANCOVA model was used for the analysis.	Baseline, Week 12
Secondary	Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event	Documented symptomatic hypoglycemia includes the typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose = 70 mg/dL (3.9 mmol/L).	Up to Week 52
Secondary	Percentage of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.	Up to Week 52