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

June 3, 2021 updated by: Lexicon Pharmaceuticals

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

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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

399

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sherbrooke, Canada, J1L 0H8
        • Investigational Site Number 1241002
      • Toronto, Canada, M3M 3E5
        • Investigational Site Number 1241005
      • Toronto, Canada, M9W 4L6
        • Investigational Site Number 1241001
      • Vancouver, Canada, V5X 0C4
        • Investigational Site Number 1241006
      • Aguascalientes, Mexico, 20230
        • Investigational Site Number 4841006
      • Aguascalientes, Mexico, 20230
        • Investigational Site Number 4841010
      • Cd. México, México, Mexico, 11410
        • Investigational Site Number 4841003
      • Chihuahua, Mexico, 31200
        • Investigational Site Number 4841004
      • Culiacan, Mexico, 80230
        • Investigational Site Number 4841001
      • Durango, Durango, Mexico, 34080
        • Investigational Site Number 4841005
      • Guadalajara, Mexico, 44600
        • Investigational Site Number 4841009
      • Mexico, Mexico, 11850
        • Investigational Site Number 4841007
      • Monterrey, Mexico, 64020
        • Investigational Site Number 4841008
      • Monterrey, Nuevo León, Mexico, 64460
        • Investigational Site Number 4841002
    • Arizona
      • Tucson, Arizona, United States, 85741
        • Investigational Site Number 8401049
      • Tucson, Arizona, United States, 85745
        • Investigational Site Number 8401026
    • California
      • Anaheim, California, United States, 92801
        • Investigational Site Number 8401028
      • Canoga Park, California, United States, 91303
        • Investigational Site Number 8401057
      • Garden Grove, California, United States, 92844-2751
        • Investigational Site Number 8401058
      • Hawaiian Gardens, California, United States, 90716
        • Investigational Site Number 8401029
      • Huntington Park, California, United States, 90255
        • Investigational Site Number 8401017
      • Long Beach, California, United States, 90806
        • Investigational Site Number 8401056
      • Long Beach, California, United States, 90807
        • Investigational Site Number 8401013
      • Los Angeles, California, United States, 90036
        • Investigational Site Number 8401063
      • Los Angeles, California, United States, 90057
        • Investigational Site Number 8401011
      • Montclair, California, United States, 91763
        • Investigational Site Number 8401022
      • Norwalk, California, United States, 90650
        • Investigational Site Number 8401039
      • San Dimas, California, United States, 91713
        • Investigational Site Number 8401035
      • Tustin, California, United States, 92780
        • Investigational Site Number 8401025
      • Van Nuys, California, United States, 91405
        • Investigational Site Number 8401015
    • Colorado
      • Denver, Colorado, United States, 80220
        • Investigational Site Number 8401031
      • Northglenn, Colorado, United States, 80234
        • Investigational Site Number 8401060
    • Florida
      • Bradenton, Florida, United States, 34201
        • Investigational Site Number 8401024
      • Clearwater, Florida, United States, 33756
        • Investigational Site Number 8401040
      • Daytona Beach, Florida, United States, 32117
        • Investigational Site Number 8401014
      • Hialeah, Florida, United States, 33012
        • Investigational Site Number 8401007
      • Homestead, Florida, United States, 33030
        • Investigational Site Number 8401046
      • Miami, Florida, United States, 33135
        • Investigational Site Number 8401018
      • Miami, Florida, United States, 33185
        • Investigational Site Number 8401008
      • Orlando, Florida, United States, 32825
        • Investigational Site Number 8401053
      • Palm Harbor, Florida, United States, 34684
        • Investigational Site Number 8401062
      • West Palm Beach, Florida, United States, 33406-5854
        • Investigational Site Number 8401061
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Investigational Site Number 8401033
    • Illinois
      • Chicago, Illinois, United States, 60602
        • Investigational Site Number 8401044
    • Iowa
      • Newton, Iowa, United States, 50208
        • Investigational Site Number 8401052
      • West Des Moines, Iowa, United States, 50265
        • Investigational Site Number 8401016
    • Kansas
      • Wichita, Kansas, United States, 67205-1138
        • Investigational Site Number 8401034
    • Louisiana
      • Lake Charles, Louisiana, United States, 70601
        • Investigational Site Number 8401038
    • North Carolina
      • Fayetteville, North Carolina, United States, 28314
        • Investigational Site Number 8401042
      • Greensboro, North Carolina, United States, 27401
        • Investigational Site Number 8401012
    • Ohio
      • Akron, Ohio, United States, 44311
        • Investigational Site Number 8401048
      • Marion, Ohio, United States, 43302
        • Investigational Site Number 8401003
    • Oregon
      • Corvallis, Oregon, United States, 97330
        • Investigational Site Number 8401020
      • Eugene, Oregon, United States, 97404
        • Investigational Site Number 8401006
    • Pennsylvania
      • Levittown, Pennsylvania, United States, 19056
        • Investigational Site Number 8401041
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Investigational Site Number 8401051
      • Greer, South Carolina, United States, 29651
        • Investigational Site Number 8401002
    • Texas
      • Fort Worth, Texas, United States, 76164
        • Investigational Site Number 8401005
      • Houston, Texas, United States, 77081
        • Investigational Site Number 8401019
      • Houston, Texas, United States, 77099
        • Investigational Site Number 8401050
      • Katy, Texas, United States, 77450
        • Investigational Site Number 8401037
      • McAllen, Texas, United States, 78504
        • Investigational Site Number 8401043
      • North Richland Hills, Texas, United States, 76180
        • Investigational Site Number 8401059
      • San Antonio, Texas, United States, 78218
        • Investigational Site Number 8401004
      • San Antonio, Texas, United States, 78229
        • Investigational Site Number 8401054
      • San Antonio, Texas, United States, 78231
        • Investigational Site Number 8401001
      • Schertz, Texas, United States, 78154
        • Investigational Site Number 8401055
      • Sugar Land, Texas, United States, 77478
        • Investigational Site Number 8401023
    • Virginia
      • Chesapeake, Virginia, United States, 23321-5205
        • Investigational Site Number 8401032
      • Suffolk, Virginia, United States, 23435-3763
        • Investigational Site Number 8401010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sotagliflozin 400 mg
Following a 2-week run-in period, participants were randomized to Sotagliflozin 400 milligrams (mg) administered as two 200 mg tablets, once daily (QD), before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Pharmaceutical form: tablet;

Route of administration: oral

Experimental: Sotagliflozin 200 mg
Following a 2-week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 Sotagliflozin tablet and 1 matching placebo tablet, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Pharmaceutical form: tablet;

Route of administration: oral

Pharmaceutical form: tablet;

Route of administration: oral

Placebo Comparator: Placebo
Following a 2-week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Pharmaceutical form: tablet;

Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Baseline to Week 26
An analysis of covariance (ANCOVA) model was used for the analysis.
Baseline to Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26
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)
Time Frame: Baseline to Week 12
An ANCOVA model was used for the analysis.
Baseline to Week 12
Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Baseline to Week 12
An ANCOVA model was used for the analysis.
Baseline to Week 12
Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo)
Time Frame: Baseline to Week 12
An ANCOVA model was used for the analysis.
Baseline to Week 12
Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26
Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26
Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Week 26
Week 26
Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Week 26
Week 26
Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo)
Time Frame: Baseline to Week 26
An ANCOVA model was used for the analysis.
Baseline to Week 26

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo)
Time Frame: Week 26
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
Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo)
Time Frame: Week 26
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2016

Primary Completion (Actual)

April 22, 2019

Study Completion (Actual)

May 17, 2019

Study Registration Dates

First Submitted

October 5, 2016

First Submitted That Met QC Criteria

October 5, 2016

First Posted (Estimate)

October 6, 2016

Study Record Updates

Last Update Posted (Actual)

June 21, 2021

Last Update Submitted That Met QC Criteria

June 3, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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