Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy

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 as Monotherapy in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02926937
• Other study ID #: EFC14833
• Secondary ID: 2016-001799-31U1
• Status: Completed
• Phase: Phase 3
• Start date: November 11, 2016
• Est. completion date: May 17, 2019

Study information

• Verified date: June 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 400 milligrams (mg) versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise.

Secondary Objectives:

• To compare Sotagliflozin 400 mg versus placebo based on:

• 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 per mercury (mmHg).

• Change from baseline in SBP for all participants.

• Change from baseline in body weight.

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

• To compare Sotagliflozin 200 mg versus placebo based on:

• Change from baseline in HbA1c.

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

• Change from baseline in body weight.

• Change from baseline in SBP for all participants.

• To evaluate the safety of Sotagliflozin 400 and 200 mg versus placebo.

Description:

Up to 34 weeks, including a Screening Period consisting of a Screening Phase of up to 2 weeks and a 2-week single-blind placebo Run-in Phase, a 26-week double-blind Treatment Period, and a 4-week post-treatment Follow-up visit to collect safety information.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 399
• Est. completion date: May 17, 2019
• Est. primary completion date: April 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Participants (male and female) with T2D, who are treated with diet and exercise only during the 12 weeks prior to screening.

• 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 kilogram per meter square (kg/m^2) at Screening.

• Hemoglobin A1c (HbA1c) <7% or >10% via central laboratory test at Screening.

• Fasting plasma glucose (FPG) >15 millimole 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.

• Women of childbearing potential not willing to use highly effective contraceptive 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 during the study.

• Treated with an antidiabetic pharmacological agent within the 12 weeks prior to the Screening Visit.

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

• History of 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 millimeter of mercury (mmHg) (systolic) or >100 mmHg (diastolic).

• History of hypertensive 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 that, according to the 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.

• 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. Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research.

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

• Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of <30 millimeter per minute (mL/min)/1.73 meter square (m^2)² at screening by the 4 variable Modification of Diet in Renal Disease (MDRD) equation.

• Participant 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.

• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.

The above information is not intended to contain all considerations relevant to a Participant 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

Locations

Country	Name	City	State
Canada	Investigational Site Number 1241002	Sherbrooke
Canada	Investigational Site Number 1241001	Toronto
Canada	Investigational Site Number 1241005	Toronto
Canada	Investigational Site Number 1241006	Vancouver
Mexico	Investigational Site Number 4841006	Aguascalientes
Mexico	Investigational Site Number 4841010	Aguascalientes
Mexico	Investigational Site Number 4841003	Cd. México, México
Mexico	Investigational Site Number 4841004	Chihuahua
Mexico	Investigational Site Number 4841001	Culiacan
Mexico	Investigational Site Number 4841005	Durango, Durango
Mexico	Investigational Site Number 4841009	Guadalajara
Mexico	Investigational Site Number 4841007	Mexico
Mexico	Investigational Site Number 4841008	Monterrey
Mexico	Investigational Site Number 4841002	Monterrey, Nuevo León
United States	Investigational Site Number 8401048	Akron	Ohio
United States	Investigational Site Number 8401028	Anaheim	California
United States	Investigational Site Number 8401051	Anderson	South Carolina
United States	Investigational Site Number 8401033	Atlanta	Georgia
United States	Investigational Site Number 8401024	Bradenton	Florida
United States	Investigational Site Number 8401057	Canoga Park	California
United States	Investigational Site Number 8401032	Chesapeake	Virginia
United States	Investigational Site Number 8401044	Chicago	Illinois
United States	Investigational Site Number 8401040	Clearwater	Florida
United States	Investigational Site Number 8401020	Corvallis	Oregon
United States	Investigational Site Number 8401014	Daytona Beach	Florida
United States	Investigational Site Number 8401031	Denver	Colorado
United States	Investigational Site Number 8401006	Eugene	Oregon
United States	Investigational Site Number 8401042	Fayetteville	North Carolina
United States	Investigational Site Number 8401005	Fort Worth	Texas
United States	Investigational Site Number 8401058	Garden Grove	California
United States	Investigational Site Number 8401012	Greensboro	North Carolina
United States	Investigational Site Number 8401002	Greer	South Carolina
United States	Investigational Site Number 8401029	Hawaiian Gardens	California
United States	Investigational Site Number 8401007	Hialeah	Florida
United States	Investigational Site Number 8401046	Homestead	Florida
United States	Investigational Site Number 8401019	Houston	Texas
United States	Investigational Site Number 8401050	Houston	Texas
United States	Investigational Site Number 8401017	Huntington Park	California
United States	Investigational Site Number 8401037	Katy	Texas
United States	Investigational Site Number 8401038	Lake Charles	Louisiana
United States	Investigational Site Number 8401041	Levittown	Pennsylvania
United States	Investigational Site Number 8401013	Long Beach	California
United States	Investigational Site Number 8401056	Long Beach	California
United States	Investigational Site Number 8401011	Los Angeles	California
United States	Investigational Site Number 8401063	Los Angeles	California
United States	Investigational Site Number 8401003	Marion	Ohio
United States	Investigational Site Number 8401043	McAllen	Texas
United States	Investigational Site Number 8401008	Miami	Florida
United States	Investigational Site Number 8401018	Miami	Florida
United States	Investigational Site Number 8401022	Montclair	California
United States	Investigational Site Number 8401052	Newton	Iowa
United States	Investigational Site Number 8401059	North Richland Hills	Texas
United States	Investigational Site Number 8401060	Northglenn	Colorado
United States	Investigational Site Number 8401039	Norwalk	California
United States	Investigational Site Number 8401053	Orlando	Florida
United States	Investigational Site Number 8401062	Palm Harbor	Florida
United States	Investigational Site Number 8401001	San Antonio	Texas
United States	Investigational Site Number 8401004	San Antonio	Texas
United States	Investigational Site Number 8401054	San Antonio	Texas
United States	Investigational Site Number 8401035	San Dimas	California
United States	Investigational Site Number 8401055	Schertz	Texas
United States	Investigational Site Number 8401010	Suffolk	Virginia
United States	Investigational Site Number 8401023	Sugar Land	Texas
United States	Investigational Site Number 8401026	Tucson	Arizona
United States	Investigational Site Number 8401049	Tucson	Arizona
United States	Investigational Site Number 8401025	Tustin	California
United States	Investigational Site Number 8401015	Van Nuys	California
United States	Investigational Site Number 8401016	West Des Moines	Iowa
United States	Investigational Site Number 8401061	West Palm Beach	Florida
United States	Investigational Site Number 8401034	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo)	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.	Week 26
Other	Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo)	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.	Week 26
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo)	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP =130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo)		Week 26
Secondary	Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo)		Week 26
Secondary	Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo)	An ANCOVA model was used for the analysis.	Baseline to Week 26