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Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03066830
Recruitment Status : Completed
First Posted : February 28, 2017
Results First Posted : May 11, 2021
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Lexicon Pharmaceuticals

Brief Summary:

Primary Objective:

To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on Hemoglobin A1c (HbA1c) reduction at Week 26 in participant with type 2 diabetes (T2D) who have inadequate glycemic control with a Sulfonylurea alone or in combination with Metformin.

Secondary Objectives:

  • To compare Sotagliflozin 400 mg versus placebo based on:
  • 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 (mm Hg).
  • Change from baseline in SBP for all participants.
  • Change from baseline in body weight.
  • Percentage of participants with HbA1c <6.5% and <7.0%.
  • To evaluate the safety of Sotagliflozin 400 mg versus placebo throughout the 79-week trial.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Sotagliflozin (SAR439954) Drug: Placebo Drug: Metformin Drug: Sulfonylurea Phase 3

Detailed Description:
The duration per participants is up to 85 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, and a 2-week post treatment Follow-up period to collect safety information.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 507 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to a Sulfonylurea Alone or in Combination With Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on a Sulfonylurea Alone or With Metformin
Actual Study Start Date : February 24, 2017
Actual Primary Completion Date : April 17, 2019
Actual Study Completion Date : April 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sotagliflozin 400 mg
Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: tablet

Route of administration: oral


Placebo Comparator: Placebo
Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Drug: Placebo

Pharmaceutical form: tablet

Route of administration: oral


Drug: Metformin

Pharmaceutical form: tablet

Route of administration: oral


Drug: Sulfonylurea

Pharmaceutical form: tablet

Route of administration: oral





Primary Outcome Measures :
  1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [ Time Frame: Baseline to Week 26 ]
    Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.


Secondary Outcome Measures :
  1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: Baseline to Week 26 ]
    Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

  2. Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg [ Time Frame: Baseline to Week 12 ]
    Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis.

  3. Change From Baseline in SBP at Week 12 for All Participants [ Time Frame: Baseline to Week 12 ]
    Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis.

  4. Change From Baseline in Body Weight at Week 26 [ Time Frame: Baseline to Week 26 ]
    Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

  5. Percentage of Participants With HbA1c <6.5% at Week 26 [ Time Frame: Week 26 ]
  6. Percentage of Participants With HbA1c <7.0% at Week 26 [ Time Frame: Week 26 ]

Other Outcome Measures:
  1. Percentage of Participants With Hypoglycemic Events [ Time Frame: Up to 79 weeks in the treatment period ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Participants with T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose [documented]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose [documented]) each at a stable dose for at least 12 weeks without a dose adjustment before screening.
  • Signed written informed consent.

Exclusion criteria:

  • At the time of screening, age <18 years or < legal age of majority, whichever is greater.
  • Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening.
  • Hemoglobin A1c (HbA1c) <7% or HbA1c >10% via central lab test at screening.
  • Fasting plasma glucose (FPG) >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.
  • Women of childbearing potential with no effective contraceptive method.
  • Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit.
  • Previous insulin use >1 month (at any time, aside from treatment of gestational diabetes).
  • History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit.
  • History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
  • History of severe hypoglycemia within 6 months prior to the Screening visit.
  • Systolic blood pressure (SBP) >180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg or history of hypertensive emergency.
  • 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).
  • 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.
  • Pregnancy, breastfeeding.
  • Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03066830


Locations
Show Show 76 study locations
Sponsors and Collaborators
Lexicon Pharmaceuticals
Sanofi
Investigators
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Study Director: Suman Wason Lexicon Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Lexicon Pharmaceuticals:
Study Protocol  [PDF] December 21, 2017
Statistical Analysis Plan  [PDF] February 20, 2020

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Responsible Party: Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03066830    
Other Study ID Numbers: EFC14835
2016-002826-35 ( EudraCT Number )
U1111-1186-2612 ( Other Identifier: UTN )
First Posted: February 28, 2017    Key Record Dates
Results First Posted: May 11, 2021
Last Update Posted: May 11, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action