Clinical trial NCT02926950: Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin
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
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: 518
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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Body Weight at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 mmHg
timeFrame: Baseline and Week 12
measure: Change From Baseline in SBP at Week 12 for All Participants
timeFrame: Baseline and Week 12
measure: Percentage of Participants With HbA1c <6.5% at Week 26
timeFrame: Week 26
measure: Percentage of Participants With HbA1c <7.0% at Week 26
timeFrame: Week 26
Other outcomes:
measure: Percentage of Participants With Hypoglycemic Events
timeFrame: Up to 79 weeks in the treatment period
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8402003
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 8402017
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 8402052
state: Arizona
city: Canoga Park
country: United States
facility: Investigational Site Number 8402056
state: California
city: Escondido
country: United States
facility: Investigational Site Number 8402020
state: California
city: Gold River
country: United States
facility: Investigational Site Number 8402028
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 8402067
state: California
city: Huntington Park
country: United States
facility: Investigational Site Number 8402025
state: California
city: La Mirada
country: United States
facility: Investigational Site Number 8402051
state: California
city: Lemon Grove
country: United States
facility: Investigational Site Number 8402042
state: California
city: Lincoln
country: United States
facility: Investigational Site Number 8402011
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 8402014
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 8402066
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8402029
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8402041
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8402001
state: California
city: San Diego
country: United States
facility: Investigational Site Number 8402043
state: California
city: San Ramon
country: United States
facility: Investigational Site Number 8402031
state: California
city: Tarzana
country: United States
facility: Investigational Site Number 8402047
state: California
city: Boynton Beach
country: United States
facility: Investigational Site Number 8402009
state: Florida
city: Daytona Beach
country: United States
facility: Investigational Site Number 8402016
state: Florida
city: Hialeah
country: United States
facility: Investigational Site Number 8402006
state: Florida
city: Hialeah
country: United States
facility: Investigational Site Number 8402035
state: Florida
city: Hialeah
country: United States
facility: Investigational Site Number 8402044
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 8402045
state: Florida
city: Miami Beach
country: United States
facility: Investigational Site Number 8402060
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8402026
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8402036
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8402064
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8402007
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8402061
state: Florida
city: Opa-locka
country: United States
facility: Investigational Site Number 8402033
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8402039
state: Florida
city: West Palm Beach
country: United States
facility: Investigational Site Number 8402063
state: Florida
city: Winter Haven
country: United States
facility: Investigational Site Number 8402038
state: Florida
city: Macon
country: United States
facility: Investigational Site Number 8402008
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 8402054
state: Illinois
city: Newton
country: United States
facility: Investigational Site Number 8402069
state: Iowa
city: West Des Moines
country: United States
facility: Investigational Site Number 8402022
state: Iowa
city: Lexington
country: United States
facility: Investigational Site Number 8402059
state: Kentucky
city: Baton Rouge
country: United States
facility: Investigational Site Number 8402068
state: Louisiana
city: Metairie
country: United States
facility: Investigational Site Number 8402012
state: Louisiana
city: New Orleans
country: United States
facility: Investigational Site Number 8402037
state: Louisiana
city: New Orleans
country: United States
facility: Investigational Site Number 8402053
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 8402021
state: Maryland
city: Omaha
country: United States
facility: Investigational Site Number 8402062
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 8402005
state: Nevada
city: Greensboro
country: United States
facility: Investigational Site Number 8402018
state: North Carolina
city: Morehead City
country: United States
facility: Investigational Site Number 8402002
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigational Site Number 8402019
state: Oklahoma
city: Eugene
country: United States
facility: Investigational Site Number 8402015
state: Oregon
city: Lansdale
country: United States
facility: Investigational Site Number 8402058
state: Pennsylvania
city: Dallas
country: United States
facility: Investigational Site Number 8402030
state: Texas
city: DeSoto
country: United States
facility: Investigational Site Number 8402050
state: Texas
city: Fort Worth
country: United States
facility: Investigational Site Number 8402010
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8402040
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8402065
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8402057
state: Texas
city: Magnolia
country: United States
facility: Investigational Site Number 8402049
state: Texas
city: Odessa
country: United States
facility: Investigational Site Number 8402046
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8402013
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8402004
state: Texas
city: Schertz
country: United States
facility: Investigational Site Number 8402023
state: Texas
city: Clinton
country: United States
facility: Investigational Site Number 8402027
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 8402032
state: Utah
city: Virginia Beach
country: United States
facility: Investigational Site Number 8402024
state: Virginia
city: Seattle
country: United States
facility: Investigational Site Number 8402034
state: Washington
city: Barrie
country: Canada
facility: Investigational Site Number 1242014
city: Brampton
country: Canada
facility: Investigational Site Number 1242004
city: Brampton
country: Canada
facility: Investigational Site Number 1242005
city: Concord
country: Canada
facility: Investigational Site Number 1242001
city: Etobicoke
country: Canada
facility: Investigational Site Number 1242007
city: Levis
country: Canada
facility: Investigational Site Number 1242010
city: Newmarket
country: Canada
facility: Investigational Site Number 1242012
city: Oakville
country: Canada
facility: Investigational Site Number 1242013
city: Pointe Claire
country: Canada
facility: Investigational Site Number 1242006
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1242008
city: Toronto
country: Canada
facility: Investigational Site Number 1242015
city: Toronto
country: Canada
facility: Investigational Site Number 1242002
city: Toronto
country: Canada
facility: Investigational Site Number 1242003
city: Vancouver
country: Canada
facility: Investigational Site Number 1242011
city: Budapest
country: Hungary
facility: Investigational Site Number 3482002
city: Budapest
country: Hungary
facility: Investigational Site Number 3482003
city: Budapest
country: Hungary
facility: Investigational Site Number 3482006
city: Debrecen
country: Hungary
facility: Investigational Site Number 3482004
city: Esztergom
country: Hungary
facility: Investigational Site Number 3482001
city: Nyiregyhaza
country: Hungary
facility: Investigational Site Number 3482007
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7032001
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7032005
city: Malacky
country: Slovakia
facility: Investigational Site Number 7032003
city: Nitra
country: Slovakia
facility: Investigational Site Number 7032002
city: Sturovo
country: Slovakia
facility: Investigational Site Number 7032004
city: Trencin
country: Slovakia
facility: Investigational Site Number 7032006
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: