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Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin (SOTA-EMPA)

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ClinicalTrials.gov Identifier: NCT03351478
Recruitment Status : Completed
First Posted : November 22, 2017
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate the superiority of sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in patients with type 2 diabetes (T2D) who have inadequate glycemic control on a Dipeptidyl Peptidase 4 Inhibitor (DPP4(i)) with or without metformin.

Secondary Objectives:

  • To demonstrate non-inferiority of sotagliflozin versus empagliflozin on HbA1c reduction.
  • To demonstrate the superiority of sotagliflozin versus placebo on 2-hour postprandial glucose (PPG) reduction, fasting plasma glucose (FPG) reduction, body weight reduction, on the proportion of patients with HbA1c <6.5% and <7.0%, and on sitting systolic blood pressure (SBP) reduction.
  • To demonstrate the superiority of sotagliflozin versus empagliflozin on HbA1c reduction and sitting SBP reduction.
  • To evaluate the safety of sotagliflozin versus empagliflozin, and placebo, throughout the trial.

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

Detailed Description:
Up to 34 weeks, including a Screening Phase of up to 2 weeks, a 2 week Run-In Phase, a 26-week double-blind Treatment Period and a 4-week post-treatment Follow-up Period to collect safety information.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 770 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 26-week Randomized, Double-blind, Controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Empagliflozin, and Placebo in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Dipeptidyl Peptidase 4 Inhibitor (DPP4(i)) With or Without Metformin
Actual Study Start Date : November 27, 2017
Actual Primary Completion Date : May 16, 2019
Actual Study Completion Date : May 16, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sotagliflozin
Sotagliflozin will be given as two tablets and one placebo capsule (identical to empagliflozin capsule in appearance), once daily before the first meal of the day.
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: tablet

Route of administration: oral


Drug: Placebo

Pharmaceutical form: capsule

Route of administration: oral


Active Comparator: Empagliflozin
Empagliflozin will be given as two placebo tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin, once daily before the first meal of the day.
Drug: Empagliflozin

Pharmaceutical form: capsule

Route of administration: oral


Drug: Placebo

Pharmaceutical form: tablet

Route of administration: oral


Placebo Comparator: Placebo
Placebo given as two placebo tablets (identical to sotagliflozin) and one placebo capsule (identical to empagliflozin) once daily before the first meal of the day.
Drug: Placebo

Pharmaceutical form: tablet

Route of administration: oral


Drug: Placebo

Pharmaceutical form: capsule

Route of administration: oral





Primary Outcome Measures :
  1. Change in HbA1c [ Time Frame: Baseline to week 26 ]
    Absolute change from baseline to week 26 in Hemoglobin A1 (HbA1c)


Secondary Outcome Measures :
  1. Change in sitting SBP in patients with SBP ≥130 mmHg at Baseline [ Time Frame: Baseline to week 12 ]
    Absolute change from baseline to week 12 in sitting systolic blood pressure (SBP)

  2. Change in 2-hour PPG following a MMTT [ Time Frame: Baseline to week 26 ]
    Absolute change in 2-hour post prandial glucose (PPG) following a mixed meal tolerance test (MMTT) from baseline to week 26

  3. Change in FPG [ Time Frame: Baseline to week 26 ]
    Absolute change in fasting plasma glucose (FPG) from baseline to week 26

  4. Change in body weight [ Time Frame: Baseline to week 26 ]
    Absolute change in body weight from baseline to week 26

  5. Change in sitting SBP in all patients [ Time Frame: Baseline to week 12 ]
    Absolute change from baseline to week 12 in sitting systolic blood pressure (SBP) in all patients

  6. Patients with HbA1c <6.5% [ Time Frame: At week 26 ]
    Proportion of patients with Hemoglobin A1c (HbA1c) <6.5% at week 26

  7. Patients with HbA1c <7.0% [ Time Frame: At week 26 ]
    Proportion of patients with Hemoglobin A1c (HbA1c) <7.0% at week 26



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 :

  • Patients with Type 2 Diabetes on Dipeptidyl peptidase-4 inhibitors(DPP4(i)) with or without metformin at a stable dose for at least 12 weeks prior to Screening Visit. Metformin dose will be ≥1500 mg per day (or maximum tolerated dose [documented]). DPP4(i) dose must be the appropriate dose as per local label.
  • Signed written informed consent.

Exclusion criteria:

  • Body mass index (BMI) ≤20 kg/m² or >45 kg/m² at Screening.
  • Use of any antidiabetic drug other than DPP4 inhibitors and metformin within 12 weeks preceding the Screening Visit.
  • Patients who have previously participated in any clinical trial of sotagliflozin/LX4211.
  • Use of a selective sodium-glucose co-transporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to screening visit.
  • Patients with severe anemia, severe cardiovascular disease (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients with short life expectancy 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.
  • Current diagnosis of chronic hepatitis and/or other clinically active liver disease requiring treatment.
  • Patients with contraindication to empagliflozin as per local labeling.
  • Patients with contraindication to metformin as per local labeling.
  • Hemoglobin A1c <7.0% or >11.0% at Screening (central laboratory).
  • Fasting plasma glucose >270 mg/dL (>15.0 mmol/L) measured by the central laboratory at Screening (Visit 1), and confirmed by a repeat test (>270 mg/dL [>15.0 mmol/L]) before Randomization.
  • Previous use of any types of insulin for >1 month (except for treatment of gestational diabetes).
  • Pregnant (confirmed by serum pregnancy test at Screening) or breast-feeding women.
  • Women of childbearing potential not willing to use highly effective method(s) of birth control during the study treatment period and follow-up period, or who are unwilling or unable to be tested for pregnancy during the study.
  • Mean of 3 separate blood pressure (BP) measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).
  • History of hypertensive crisis resulting in emergency medical care within 12 weeks prior to Screening Visit.
  • Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.
  • Laboratory findings with the central laboratory tests at Visit 1:
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range (ULN);
  • Total bilirubin >1.5 times the ULN (except in case of Gilbert's syndrome);
  • Neutrophils <1 500/mm3 (or according to ethnic group) and/or platelets <100 000/mm3;
  • Amylase and/or lipase >3 times the ULN;
  • Patients with renal impairment as defined by the estimated glomerular filtration rate (eGFR) criterion that precludes initiation of empagliflozin as per the approved local label (eg, <45 mL/min/1.73 m2 in US; <60 mL/min/1.73 m2 in EU).
  • Secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
  • If the patient is on hypertensive medications, the antihypertensive has been changed in the 8 weeks prior to Screening (new drug or new dose).

The above information is not intended to contain all considerations relevant to a patient'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): NCT03351478


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Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03351478     History of Changes
Other Study ID Numbers: EFC14867
2016-001803-22 ( EudraCT Number )
U1111-1190-7607 ( Other Identifier: UTN )
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
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
Empagliflozin
(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