Clinical trial NCT03332771: Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Participants With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy
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
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: 2017-11-06
Enrollment: 954
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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in Hemoglobin A1c at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Body Weight at Week 26 and 52
timeFrame: Baseline, Week 26, Week 52
measure: Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event
timeFrame: Up to Week 52
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to Week 52
Other outcomes:
measure: Percentage of Participants With Hypoglycemic Events
timeFrame: Up to Week 52
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8407040
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 8407048
state: Alabama
city: Little Rock
country: United States
facility: Investigational Site Number 8407035
state: Arkansas
city: Anaheim
country: United States
facility: Investigational Site Number 8407051
state: California
city: Canoga Park
country: United States
facility: Investigational Site Number 8407065
state: California
city: Carmichael
country: United States
facility: Investigational Site Number 8407078
state: California
city: Downey
country: United States
facility: Investigational Site Number 8407089
state: California
city: Gold River
country: United States
facility: Investigational Site Number 8407011
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 8407044
state: California
city: Huntington Park
country: United States
facility: Investigational Site Number 8407006
state: California
city: Lemon Grove
country: United States
facility: Investigational Site Number 8407037
state: California
city: Lomita
country: United States
facility: Investigational Site Number 8407100
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 8407033
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8407019
state: California
city: Northridge
country: United States
facility: Investigational Site Number 8407098
state: California
city: Norwalk
country: United States
facility: Investigational Site Number 8407094
state: California
city: Pomona
country: United States
facility: Investigational Site Number 8407106
state: California
city: Rancho Cucamonga
country: United States
facility: Investigational Site Number 8407096
state: California
city: Sacramento
country: United States
facility: Investigational Site Number 8407036
state: California
city: Tarzana
country: United States
facility: Investigational Site Number 8407084
state: California
city: Upland
country: United States
facility: Investigational Site Number 8407034
state: California
city: Van Nuys
country: United States
facility: Investigational Site Number 8407032
state: California
city: Walnut Creek
country: United States
facility: Investigational Site Number 8407004
state: California
city: Wildomar
country: United States
facility: Investigational Site Number 8407117
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 8407045
state: Colorado
city: Bradenton
country: United States
facility: Investigational Site Number 8407074
state: Florida
city: Clearwater
country: United States
facility: Investigational Site Number 8407027
state: Florida
city: Cooper City
country: United States
facility: Investigational Site Number 8407103
state: Florida
city: Coral Gables
country: United States
facility: Investigational Site Number 8407021
state: Florida
city: Lake Worth
country: United States
facility: Investigational Site Number 8407062
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8407121
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8407024
state: Florida
city: Palmetto Bay
country: United States
facility: Investigational Site Number 8407038
state: Florida
city: Pembroke Pines
country: United States
facility: Investigational Site Number 8407093
state: Florida
city: Spring Hill
country: United States
facility: Investigational Site Number 8407107
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 8407091
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 8407113
state: Florida
city: West Palm Beach
country: United States
facility: Investigational Site Number 8407092
state: Florida
city: Winter Haven
country: United States
facility: Investigational Site Number 8407115
state: Florida
city: Chicago
country: United States
facility: Investigational Site Number 8407017
state: Illinois
city: Elgin
country: United States
facility: Investigational Site Number 8407018
state: Illinois
city: Gurnee
country: United States
facility: Investigational Site Number 8407046
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 8407119
state: Illinois
city: Waterloo
country: United States
facility: Investigational Site Number 8407075
state: Iowa
city: West Des Moines
country: United States
facility: Investigational Site Number 8407120
state: Iowa
city: Topeka
country: United States
facility: Investigational Site Number 8407095
state: Kansas
city: Wichita
country: United States
facility: Investigational Site Number 8407083
state: Kansas
city: Lexington
country: United States
facility: Investigational Site Number 8407043
state: Kentucky
city: Lexington
country: United States
facility: Investigational Site Number 8407087
state: Kentucky
city: Lake Charles
country: United States
facility: Investigational Site Number 8407060
state: Louisiana
city: New Orleans
country: United States
facility: Investigational Site Number 8407058
state: Louisiana
city: New Orleans
country: United States
facility: Investigational Site Number 8407009
state: Louisiana
city: Zachary
country: United States
facility: Investigational Site Number 8407079
state: Louisiana
city: Baltimore
country: United States
facility: Investigational Site Number 8407085
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 8407001
state: Maryland
city: Troy
country: United States
facility: Investigational Site Number 8407069
state: Michigan
city: Olive Branch
country: United States
facility: Investigational Site Number 8407110
state: Mississippi
city: Bridgeton
country: United States
facility: Investigational Site Number 8407054
state: Missouri
city: Norfolk
country: United States
facility: Investigational Site Number 8407049
state: Nebraska
city: Omaha
country: United States
facility: Investigational Site Number 8407039
state: Nebraska
city: Papillion
country: United States
facility: Investigational Site Number 8407061
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 8407108
state: Nevada
city: Albuquerque
country: United States
facility: Investigational Site Number 8407050
state: New Mexico
city: New York
country: United States
facility: Investigational Site Number 8407116
state: New York
city: New York
country: United States
facility: Investigational Site Number 8407086
state: New York
city: New York
country: United States
facility: Investigational Site Number 8407122
state: New York
city: West Seneca
country: United States
facility: Investigational Site Number 8407123
state: New York
city: Greensboro
country: United States
facility: Investigational Site Number 8407020
state: North Carolina
city: Lenoir
country: United States
facility: Investigational Site Number 8407114
state: North Carolina
city: Morehead City
country: United States
facility: Investigational Site Number 8407015
state: North Carolina
city: Salisbury
country: United States
facility: Investigational Site Number 8407030
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 8407041
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 8407101
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 8407099
state: Ohio
city: Lyndhurst
country: United States
facility: Investigational Site Number 8407081
state: Ohio
city: Norman
country: United States
facility: Investigational Site Number 8407057
state: Oklahoma
city: Oklahoma City
country: United States
facility: Investigational Site Number 8407073
state: Oklahoma
city: Eugene
country: United States
facility: Investigational Site Number 8407068
state: Oregon
city: Beaver
country: United States
facility: Investigational Site Number 8407104
state: Pennsylvania
city: Hatboro
country: United States
facility: Investigational Site Number 8407025
state: Pennsylvania
city: Lansdale
country: United States
facility: Investigational Site Number 8407053
state: Pennsylvania
city: Charleston
country: United States
facility: Investigational Site Number 8407016
state: South Carolina
city: Greer
country: United States
facility: Investigational Site Number 8407071
state: South Carolina
city: Mount Pleasant
country: United States
facility: Investigational Site Number 8407022
state: South Carolina
city: Mount Pleasant
country: United States
facility: Investigational Site Number 8407031
state: South Carolina
city: Jefferson City
country: United States
facility: Investigational Site Number 8407014
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 8407002
state: Tennessee
city: Memphis
country: United States
facility: Investigational Site Number 8407056
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 8407026
state: Texas
city: Beaumont
country: United States
facility: Investigational Site Number 8407029
state: Texas
city: Carrollton
country: United States
facility: Investigational Site Number 8407070
state: Texas
city: Corpus Christi
country: United States
facility: Investigational Site Number 8407102
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8407023
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8407111
state: Texas
city: Fort Worth
country: United States
facility: Investigational Site Number 8407013
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8407080
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8407088
state: Texas
city: Katy
country: United States
facility: Investigational Site Number 8407090
state: Texas
city: Lampasas
country: United States
facility: Investigational Site Number 8407042
state: Texas
city: Lufkin
country: United States
facility: Investigational Site Number 8407067
state: Texas
city: Lufkin
country: United States
facility: Investigational Site Number 8407118
state: Texas
city: McAllen
country: United States
facility: Investigational Site Number 8407059
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 8407012
state: Texas
city: Plano
country: United States
facility: Investigational Site Number 8407007
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8407005
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8407064
state: Texas
city: Schertz
country: United States
facility: Investigational Site Number 8407010
state: Texas
city: Splendora
country: United States
facility: Investigational Site Number 8407076
state: Texas
city: Clinton
country: United States
facility: Investigational Site Number 8407063
state: Utah
city: Holladay
country: United States
facility: Investigational Site Number 8407055
state: Utah
city: Ogden
country: United States
facility: Investigational Site Number 8407097
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 8407072
state: Utah
city: Manassas
country: United States
facility: Investigational Site Number 8407124
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 8407105
state: Virginia
city: Renton
country: United States
facility: Investigational Site Number 8407028
state: Washington
city: Gabrovo
country: Bulgaria
facility: Investigational Site Number 1007002
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1007008
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1007003
city: Ruse
country: Bulgaria
facility: Investigational Site Number 1007001
city: Smolyan
country: Bulgaria
facility: Investigational Site Number 1007004
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1007009
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 1007005
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 1007006
city: Varna
country: Bulgaria
facility: Investigational Site Number 1007007
city: Balatonfured
country: Hungary
facility: Investigational Site Number 3487005
city: Budapest
country: Hungary
facility: Investigational Site Number 3487001
city: Budapest
country: Hungary
facility: Investigational Site Number 3487010
city: Debrecen
country: Hungary
facility: Investigational Site Number 3487006
city: Debrecen
country: Hungary
facility: Investigational Site Number 3487008
city: Kecskemet
country: Hungary
facility: Investigational Site Number 3487002
city: Nyiregyhaza
country: Hungary
facility: Investigational Site Number 3487007
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number 3487004
city: Bardejov
country: Slovakia
facility: Investigational Site Number 7037004
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7037008
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7037007
city: Kosice
country: Slovakia
facility: Investigational Site Number 7037005
city: Levice
country: Slovakia
facility: Investigational Site Number 7037002
city: Nitra
country: Slovakia
facility: Investigational Site Number 7037010
city: Roznava
country: Slovakia
facility: Investigational Site Number 7037009
city: Sabinov
country: Slovakia
facility: Investigational Site Number 7037001
city: Trnava
country: Slovakia
facility: Investigational Site Number 7037003
city: Vrutky
country: Slovakia
facility: Investigational Site Number 7037006
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: