Clinical trial NCT02926937: Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2016-10-06
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Baseline to Week 26
measure: Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo)
timeFrame: Baseline to Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Baseline to Week 26
measure: 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)
timeFrame: Baseline to Week 12
measure: Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Baseline to Week 12
measure: Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo)
timeFrame: Baseline to Week 12
measure: Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Baseline to Week 26
measure: Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo)
timeFrame: Baseline to Week 26
measure: Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Week 26
measure: Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Week 26
measure: Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo)
timeFrame: Baseline to Week 26
Other outcomes:
measure: Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo)
timeFrame: Week 26
measure: Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo)
timeFrame: Week 26
Locations:
city: Tucson
country: United States
facility: Investigational Site Number 8401049
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 8401026
state: Arizona
city: Anaheim
country: United States
facility: Investigational Site Number 8401028
state: California
city: Canoga Park
country: United States
facility: Investigational Site Number 8401057
state: California
city: Garden Grove
country: United States
facility: Investigational Site Number 8401058
state: California
city: Hawaiian Gardens
country: United States
facility: Investigational Site Number 8401029
state: California
city: Huntington Park
country: United States
facility: Investigational Site Number 8401017
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 8401056
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 8401013
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8401063
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8401011
state: California
city: Montclair
country: United States
facility: Investigational Site Number 8401022
state: California
city: Norwalk
country: United States
facility: Investigational Site Number 8401039
state: California
city: San Dimas
country: United States
facility: Investigational Site Number 8401035
state: California
city: Tustin
country: United States
facility: Investigational Site Number 8401025
state: California
city: Van Nuys
country: United States
facility: Investigational Site Number 8401015
state: California
city: Denver
country: United States
facility: Investigational Site Number 8401031
state: Colorado
city: Northglenn
country: United States
facility: Investigational Site Number 8401060
state: Colorado
city: Bradenton
country: United States
facility: Investigational Site Number 8401024
state: Florida
city: Clearwater
country: United States
facility: Investigational Site Number 8401040
state: Florida
city: Daytona Beach
country: United States
facility: Investigational Site Number 8401014
state: Florida
city: Hialeah
country: United States
facility: Investigational Site Number 8401007
state: Florida
city: Homestead
country: United States
facility: Investigational Site Number 8401046
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8401018
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8401008
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8401053
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 8401062
state: Florida
city: West Palm Beach
country: United States
facility: Investigational Site Number 8401061
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 8401033
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 8401044
state: Illinois
city: Newton
country: United States
facility: Investigational Site Number 8401052
state: Iowa
city: West Des Moines
country: United States
facility: Investigational Site Number 8401016
state: Iowa
city: Wichita
country: United States
facility: Investigational Site Number 8401034
state: Kansas
city: Lake Charles
country: United States
facility: Investigational Site Number 8401038
state: Louisiana
city: Fayetteville
country: United States
facility: Investigational Site Number 8401042
state: North Carolina
city: Greensboro
country: United States
facility: Investigational Site Number 8401012
state: North Carolina
city: Akron
country: United States
facility: Investigational Site Number 8401048
state: Ohio
city: Marion
country: United States
facility: Investigational Site Number 8401003
state: Ohio
city: Corvallis
country: United States
facility: Investigational Site Number 8401020
state: Oregon
city: Eugene
country: United States
facility: Investigational Site Number 8401006
state: Oregon
city: Levittown
country: United States
facility: Investigational Site Number 8401041
state: Pennsylvania
city: Anderson
country: United States
facility: Investigational Site Number 8401051
state: South Carolina
city: Greer
country: United States
facility: Investigational Site Number 8401002
state: South Carolina
city: Fort Worth
country: United States
facility: Investigational Site Number 8401005
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8401019
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8401050
state: Texas
city: Katy
country: United States
facility: Investigational Site Number 8401037
state: Texas
city: McAllen
country: United States
facility: Investigational Site Number 8401043
state: Texas
city: North Richland Hills
country: United States
facility: Investigational Site Number 8401059
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8401004
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8401054
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8401001
state: Texas
city: Schertz
country: United States
facility: Investigational Site Number 8401055
state: Texas
city: Sugar Land
country: United States
facility: Investigational Site Number 8401023
state: Texas
city: Chesapeake
country: United States
facility: Investigational Site Number 8401032
state: Virginia
city: Suffolk
country: United States
facility: Investigational Site Number 8401010
state: Virginia
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1241002
city: Toronto
country: Canada
facility: Investigational Site Number 1241005
city: Toronto
country: Canada
facility: Investigational Site Number 1241001
city: Vancouver
country: Canada
facility: Investigational Site Number 1241006
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 4841006
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 4841010
city: Cd. México, México
country: Mexico
facility: Investigational Site Number 4841003
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4841004
city: Culiacan
country: Mexico
facility: Investigational Site Number 4841001
city: Durango, Durango
country: Mexico
facility: Investigational Site Number 4841005
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4841009
city: Mexico
country: Mexico
facility: Investigational Site Number 4841007
city: Monterrey, Nuevo León
country: Mexico
facility: Investigational Site Number 4841002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4841008
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: