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

NCT02926950 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC148342016-001800-49U1111-1181-6145
• Study Type: interventional
• Target: 518
• Locations: 4 countries
• Sites: 93

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26

  Baseline and Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline and Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline and Week 26

• Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 mmHg

  Baseline and Week 12

• Change From Baseline in SBP at Week 12 for All Participants

  Baseline and Week 12

Other Outcomes (1)

• Percentage of Participants With Hypoglycemic Events

  Up to 79 weeks in the treatment period

Study Arms (2)

Sotagliflozin 400 mg + Metformin

EXPERIMENTAL

Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.

Drug: Sotagliflozin (SAR439954); Drug: Metformin

Placebo + Metformin

PLACEBO COMPARATOR

Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.

Drug: Placebo; Drug: Metformin

Interventions

Sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablet. Route of administration: oral.

Sotagliflozin 400 mg + Metformin

Placebo DRUG

Pharmaceutical form: tablet. Route of administration: oral.

Placebo + Metformin

Metformin DRUG

Pharmaceutical form: tablet. Route of administration: oral.

Placebo + Metformin; Sotagliflozin 400 mg + Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (93)

Investigational Site Number 8402003

Birmingham, Alabama, 35205, United States

Location

Investigational Site Number 8402017

Birmingham, Alabama, 35294, United States

Location

Investigational Site Number 8402052

Phoenix, Arizona, 85018, United States

Location

Investigational Site Number 8402056

Canoga Park, California, 91303, United States

Location

Investigational Site Number 8402020

Escondido, California, 92025, United States

Location

Investigational Site Number 8402028

Gold River, California, 95670, United States

Location

Investigational Site Number 8402067

Greenbrae, California, 94904, United States

Location

Investigational Site Number 8402025

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8402051

La Mirada, California, 90638, United States

Location

Investigational Site Number 8402042

Lemon Grove, California, 91945, United States

Location

Investigational Site Number 8402011

Lincoln, California, 95648, United States

Location

Investigational Site Number 8402014

Long Beach, California, 90807, United States

Location

Investigational Site Number 8402066

Long Beach, California, 90807, United States

Location

Investigational Site Number 8402029

Los Angeles, California, 90022, United States

Location

Investigational Site Number 8402041

Los Angeles, California, 90036, United States

Location

Investigational Site Number 8402001

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8402043

San Diego, California, 92103, United States

Location

Investigational Site Number 8402031

San Ramon, California, 94582, United States

Location

Investigational Site Number 8402047

Tarzana, California, 91356, United States

Location

Investigational Site Number 8402009

Boynton Beach, Florida, 33472, United States

Location

Investigational Site Number 8402016

Daytona Beach, Florida, 32117, United States

Location

Investigational Site Number 8402006

Hialeah, Florida, 33012, United States

Location

Investigational Site Number 8402035

Hialeah, Florida, 33012, United States

Location

Investigational Site Number 8402044

Hialeah, Florida, 33012, United States

Location

Investigational Site Number 8402045

Jacksonville, Florida, 32256, United States

Location

Investigational Site Number 8402026

Miami, Florida, 33126, United States

Location

Investigational Site Number 8402036

Miami, Florida, 33143, United States

Location

Investigational Site Number 8402064

Miami, Florida, 33183, United States

Location

Investigational Site Number 8402007

Miami, Florida, 33185, United States

Location

Investigational Site Number 8402061

Miami, Florida, 33186, United States

Location

Investigational Site Number 8402060

Miami Beach, Florida, 33140-3608, United States

Location

Investigational Site Number 8402033

Opa-locka, Florida, 33054, United States

Location

Investigational Site Number 8402039

Orlando, Florida, 32825, United States

Location

Investigational Site Number 8402063

West Palm Beach, Florida, 33406-5854, United States

Location

Investigational Site Number 8402038

Winter Haven, Florida, 33880, United States

Location

Investigational Site Number 8402008

Macon, Georgia, 31210, United States

Location

Investigational Site Number 8402054

Chicago, Illinois, 60607, United States

Location

Investigational Site Number 8402069

Newton, Iowa, 50208, United States

Location

Investigational Site Number 8402022

West Des Moines, Iowa, 50265, United States

Location

Investigational Site Number 8402059

Lexington, Kentucky, 40503, United States

Location

Investigational Site Number 8402068

Baton Rouge, Louisiana, 70808-4124, United States

Location

Investigational Site Number 8402012

Metairie, Louisiana, 70006, United States

Location

Investigational Site Number 8402037

New Orleans, Louisiana, 70119-6302, United States

Location

Investigational Site Number 8402053

New Orleans, Louisiana, 70124, United States

Location

Investigational Site Number 8402021

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 8402062

Omaha, Nebraska, 68114-3755, United States

Location

Investigational Site Number 8402005

Las Vegas, Nevada, 89148, United States

Location

Investigational Site Number 8402018

Greensboro, North Carolina, 27401, United States

Location

Investigational Site Number 8402002

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 8402019

Oklahoma City, Oklahoma, 73104, United States

Location

Investigational Site Number 8402015

Eugene, Oregon, 97404-3233, United States

Location

Investigational Site Number 8402058

Lansdale, Pennsylvania, 19446-1002, United States

Location

Investigational Site Number 8402030

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8402050

DeSoto, Texas, 75115, United States

Location

Investigational Site Number 8402010

Fort Worth, Texas, 76164, United States

Location

Investigational Site Number 8402040

Houston, Texas, 77008, United States

Location

Investigational Site Number 8402065

Houston, Texas, 77058, United States

Location

Investigational Site Number 8402057

Houston, Texas, 77079, United States

Location

Investigational Site Number 8402049

Magnolia, Texas, 77355, United States

Location

Investigational Site Number 8402046

Odessa, Texas, 79761, United States

Location

Investigational Site Number 8402013

San Antonio, Texas, 78218, United States

Location

Investigational Site Number 8402004

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8402023

Schertz, Texas, 78154, United States

Location

Investigational Site Number 8402027

Clinton, Utah, 84015, United States

Location

Investigational Site Number 8402032

Salt Lake City, Utah, 84107, United States

Location

Investigational Site Number 8402024

Virginia Beach, Virginia, 23454, United States

Location

Investigational Site Number 8402034

Seattle, Washington, 98105, United States

Location

Investigational Site Number 1242014

Barrie, L4M 7G1, Canada

Location

Investigational Site Number 1242004

Brampton, L6S 0C6, Canada

Location

Investigational Site Number 1242005

Brampton, L6T 0G1, Canada

Location

Investigational Site Number 1242001

Concord, L4K 4M2, Canada

Location

Investigational Site Number 1242007

Etobicoke, M9R 4E1, Canada

Location

Investigational Site Number 1242010

Lévis, G6W 0M5, Canada

Location

Investigational Site Number 1242012

Newmarket, L3Y 5G8, Canada

Location

Investigational Site Number 1242013

Oakville, L6M 1M1, Canada

Location

Investigational Site Number 1242006

Pointe-Claire, H9R 4S3, Canada

Location

Investigational Site Number 1242008

Sherbrooke, J1L 0H8, Canada

Location

Investigational Site Number 1242015

Toronto, M3M 3E5, Canada

Location

Investigational Site Number 1242002

Toronto, M4G 3E8, Canada

Location

Investigational Site Number 1242003

Toronto, M9W 4L6, Canada

Location

Investigational Site Number 1242011

Vancouver, V5X 0C4, Canada

Location

Investigational Site Number 3482002

Budapest, 1033, Hungary

Location

Investigational Site Number 3482003

Budapest, 1088, Hungary

Location

Investigational Site Number 3482006

Budapest, 1213, Hungary

Location

Investigational Site Number 3482004

Debrecen, 4025, Hungary

Location

Investigational Site Number 3482001

Esztergom, 2500, Hungary

Location

Investigational Site Number 3482007

Nyíregyháza, 4400, Hungary

Location

Investigational Site Number 7032001

Bratislava, 851 01, Slovakia

Location

Investigational Site Number 7032005

Bratislava, 851 01, Slovakia

Location

Investigational Site Number 7032003

Malacky, 901 01, Slovakia

Location

Investigational Site Number 7032002

Nitra, 949 11, Slovakia

Location

Investigational Site Number 7032004

Štúrovo, 943 01, Slovakia

Location

Investigational Site Number 7032006

Trenčín, 911 01, Slovakia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Medical Affairs
• Organization: Lexicon Pharmaceuticals, Inc.

medical-information@lexpharma.com

(510) 338-6064

Study Officials

• Suman Wason, MD

  Lexicon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 6, 2016
• Study Start: November 1, 2016
• Primary Completion: February 26, 2019
• Study Completion: March 22, 2019
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

SL (6); HU (6); CA (14); US (67)