Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02926950
• Other study ID #: EFC14834
• Secondary ID: 2016-001800-49U1
• Status: Completed
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: March 22, 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 superiority of Sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control with metformin.

Secondary Objectives:

• To compare Sotagliflozin versus placebo for.

• Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.

• Change from baseline in fasting plasma glucose (FPG).

• Change from Baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter of mercury (mmHg).

• Change from baseline in SBP for all participants.

• Change from baseline in body weight.

• Proportion of participants with HbA1c <6.5% and <7.0%.

• To evaluate the safety of Sotagliflozin versus placebo.

Description:

The duration of the study period is up to 87 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks and a 2 week single blind Run-in phase, a 26 week double-blind Core Treatment Period, a 53-week double-blind Extension Period, a 4 week post treatment Follow-up period to collect safety information.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 518
• Est. completion date: March 22, 2019
• Est. primary completion date: February 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Participants with Type 2 Diabetes currently treated with diet and exercise and on metformin at a stable dose =1500 milligrams per day (mg/day) for at least 12 weeks. However, participants on metformin at a dose <1500 mg/day at the time of enrollment (stable dose for at least 12 weeks before enrollment) may be eligible for screening if documentation of lack of tolerance of a metformin dose =1500 mg/day can be provided.

• Signed written informed consent.

Exclusion criteria:

• Age <18 years at Screening or < legal age of majority, whichever is greater.

• Type 1 diabetes mellitus.

• Body Mass Index (BMI) =20 or >45 kilograms per meter square (kg/m^2) at Screening

• Hemoglobin A1c <7% or >10% via central laboratory test at screening.

• Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligrams 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.

• Women of childbearing potential not willing to use highly effective method(s) of birth control or who are unwilling or unable to be tested for pregnancy during the study.

• Treated with an antidiabetic pharmacological regimen other than metformin =1500 mg per day (or maximum tolerated dose) within the 12 weeks preceding the Screening Visit.

• Previous use of any types of insulin for >1 month (at any time, aside from pregnancy for treatment of gestational diabetes).

• History of prior gastric surgical procedure, including gastric banding, within 3 years before the Screening Visit.

• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.

• Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic blood pressure [DBP]).

• History of hypertensive urgency or emergency within 12 weeks prior to Screening.

• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association [NYHA] IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with short life expectancy making 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.

• Total bilirubin: >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).

• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.

• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from screening or randomization, whichever is longer.

• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

• Participants is unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the participants diary, or comply with study visits and other study procedures as required per protocol.

• Contraindication to metformin as per local labelling.

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 (SAR439954)
Pharmaceutical form: tablet. Route of administration: oral.
• Placebo
Pharmaceutical form: tablet. Route of administration: oral.
• Metformin
Pharmaceutical form: tablet. Route of administration: oral.

Locations

Country	Name	City	State
Canada	Investigational Site Number 1242014	Barrie
Canada	Investigational Site Number 1242004	Brampton
Canada	Investigational Site Number 1242005	Brampton
Canada	Investigational Site Number 1242001	Concord
Canada	Investigational Site Number 1242007	Etobicoke
Canada	Investigational Site Number 1242010	Levis
Canada	Investigational Site Number 1242012	Newmarket
Canada	Investigational Site Number 1242013	Oakville
Canada	Investigational Site Number 1242006	Pointe Claire
Canada	Investigational Site Number 1242008	Sherbrooke
Canada	Investigational Site Number 1242002	Toronto
Canada	Investigational Site Number 1242003	Toronto
Canada	Investigational Site Number 1242015	Toronto
Canada	Investigational Site Number 1242011	Vancouver
Hungary	Investigational Site Number 3482002	Budapest
Hungary	Investigational Site Number 3482003	Budapest
Hungary	Investigational Site Number 3482006	Budapest
Hungary	Investigational Site Number 3482004	Debrecen
Hungary	Investigational Site Number 3482001	Esztergom
Hungary	Investigational Site Number 3482007	Nyiregyhaza
Slovakia	Investigational Site Number 7032001	Bratislava
Slovakia	Investigational Site Number 7032005	Bratislava
Slovakia	Investigational Site Number 7032003	Malacky
Slovakia	Investigational Site Number 7032002	Nitra
Slovakia	Investigational Site Number 7032004	Sturovo
Slovakia	Investigational Site Number 7032006	Trencin
United States	Investigational Site Number 8402068	Baton Rouge	Louisiana
United States	Investigational Site Number 8402003	Birmingham	Alabama
United States	Investigational Site Number 8402017	Birmingham	Alabama
United States	Investigational Site Number 8402009	Boynton Beach	Florida
United States	Investigational Site Number 8402056	Canoga Park	California
United States	Investigational Site Number 8402054	Chicago	Illinois
United States	Investigational Site Number 8402027	Clinton	Utah
United States	Investigational Site Number 8402030	Dallas	Texas
United States	Investigational Site Number 8402016	Daytona Beach	Florida
United States	Investigational Site Number 8402050	DeSoto	Texas
United States	Investigational Site Number 8402020	Escondido	California
United States	Investigational Site Number 8402015	Eugene	Oregon
United States	Investigational Site Number 8402010	Fort Worth	Texas
United States	Investigational Site Number 8402028	Gold River	California
United States	Investigational Site Number 8402067	Greenbrae	California
United States	Investigational Site Number 8402018	Greensboro	North Carolina
United States	Investigational Site Number 8402006	Hialeah	Florida
United States	Investigational Site Number 8402035	Hialeah	Florida
United States	Investigational Site Number 8402044	Hialeah	Florida
United States	Investigational Site Number 8402040	Houston	Texas
United States	Investigational Site Number 8402057	Houston	Texas
United States	Investigational Site Number 8402065	Houston	Texas
United States	Investigational Site Number 8402025	Huntington Park	California
United States	Investigational Site Number 8402045	Jacksonville	Florida
United States	Investigational Site Number 8402051	La Mirada	California
United States	Investigational Site Number 8402058	Lansdale	Pennsylvania
United States	Investigational Site Number 8402005	Las Vegas	Nevada
United States	Investigational Site Number 8402042	Lemon Grove	California
United States	Investigational Site Number 8402059	Lexington	Kentucky
United States	Investigational Site Number 8402011	Lincoln	California
United States	Investigational Site Number 8402014	Long Beach	California
United States	Investigational Site Number 8402066	Long Beach	California
United States	Investigational Site Number 8402001	Los Angeles	California
United States	Investigational Site Number 8402029	Los Angeles	California
United States	Investigational Site Number 8402041	Los Angeles	California
United States	Investigational Site Number 8402008	Macon	Georgia
United States	Investigational Site Number 8402049	Magnolia	Texas
United States	Investigational Site Number 8402012	Metairie	Louisiana
United States	Investigational Site Number 8402007	Miami	Florida
United States	Investigational Site Number 8402026	Miami	Florida
United States	Investigational Site Number 8402036	Miami	Florida
United States	Investigational Site Number 8402061	Miami	Florida
United States	Investigational Site Number 8402064	Miami	Florida
United States	Investigational Site Number 8402060	Miami Beach	Florida
United States	Investigational Site Number 8402002	Morehead City	North Carolina
United States	Investigational Site Number 8402037	New Orleans	Louisiana
United States	Investigational Site Number 8402053	New Orleans	Louisiana
United States	Investigational Site Number 8402069	Newton	Iowa
United States	Investigational Site Number 8402046	Odessa	Texas
United States	Investigational Site Number 8402019	Oklahoma City	Oklahoma
United States	Investigational Site Number 8402062	Omaha	Nebraska
United States	Investigational Site Number 8402033	Opa-locka	Florida
United States	Investigational Site Number 8402039	Orlando	Florida
United States	Investigational Site Number 8402052	Phoenix	Arizona
United States	Investigational Site Number 8402021	Rockville	Maryland
United States	Investigational Site Number 8402032	Salt Lake City	Utah
United States	Investigational Site Number 8402004	San Antonio	Texas
United States	Investigational Site Number 8402013	San Antonio	Texas
United States	Investigational Site Number 8402043	San Diego	California
United States	Investigational Site Number 8402031	San Ramon	California
United States	Investigational Site Number 8402023	Schertz	Texas
United States	Investigational Site Number 8402034	Seattle	Washington
United States	Investigational Site Number 8402047	Tarzana	California
United States	Investigational Site Number 8402024	Virginia Beach	Virginia
United States	Investigational Site Number 8402022	West Des Moines	Iowa
United States	Investigational Site Number 8402063	West Palm Beach	Florida
United States	Investigational Site Number 8402038	Winter Haven	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada,  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]. Participants may be reported in more than one category.	Up to 79 weeks in the treatment period
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline and Week 26
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 and Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model was used for the analysis.	Baseline and Week 26
Secondary	Change From Baseline in Body Weight at Week 26	An ANCOVA model was used for the analysis.	Baseline and Week 26
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP =130 mmHg	An ANCOVA model was used for the analysis.	Baseline and Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline and 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