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

ID: NCT03351478
Status: Recruiting
Phase: Phase 3
Start Date: November 27, 2017
First Submitted: November 20, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Bulgaria, Canada, United States
Conditions: Type 2 Diabetes Mellitus
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Study Description

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.

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.
Condition or disease Intervention/treatment Phase

Type 2 Diabetes Mellitus

Drug: Sotagliflozin (SAR439954)
Other Names
Drug: Empagliflozin
Other Names
Drug: Placebo
Other Names
Drug: Placebo
Other Names
Phase 3

Tracking Information

First Submitted DateNovember 20, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateNovember 27, 2017
Anticipated Completion DateMay 01, 2019
Actual Primary Completion DateMay 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change in HbA1c [Time Frame: Baseline to week 26]

    Absolute change from baseline to week 26 in Hemoglobin A1 (HbA1c)

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • 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)

  • 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

  • Change in FPG [Time Frame: Baseline to week 26]

    Absolute change in fasting plasma glucose (FPG) from baseline to week 26

  • Change in body weight [Time Frame: Baseline to week 26]

    Absolute change in body weight from baseline to week 26

  • 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

  • Patients with HbA1c <6.5% [Time Frame: At week 26]

    Proportion of patients with Hemoglobin A1c (HbA1c) <6.5% at week 26

  • Patients with HbA1c <7.0% [Time Frame: At week 26]

    Proportion of patients with Hemoglobin A1c (HbA1c) <7.0% at week 26

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy 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
Official TitleA 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
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.

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.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
700
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Type 2 Diabetes Mellitus
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: tablet Route of administration: oral

Other Names
Drug: Empagliflozin

Pharmaceutical form: capsule Route of administration: oral

Other Names
Drug: Placebo

Pharmaceutical form: tablet Route of administration: oral

Other Names
Drug: Placebo

Pharmaceutical form: capsule Route of administration: oral

Other Names
Study Groups/Cohorts
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.

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.

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.

Study Arms
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

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 : 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: capsule 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

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 : Placebo
Pharmaceutical form: capsule Route of administration: oral

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

Arm Intervention/Treatment
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
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 : Placebo
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
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
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 : Placebo
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)

Recruitment Information

Recruitment Status:Recruiting
Enrollment700
Completion DateMay 01, 2019
Eligibility 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-2 (SGLT2) inhibitor (eg, canagliflozin, dapagliflozin, or empagliflozin) within 12 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 BP measurements >180 mmHg (SBP) or >100 mmHg (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 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.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Bulgaria
Canada
United States

Administrative Information

NCT Number:NCT03351478
Other Study ID Numbers
EFC14867
2016-001803-22
U1111-1190-7607
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi