Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Subjects With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy

ID: NCT03332771
Status: Recruiting
Phase: Phase 3
Start Date: December 01, 2017
First Submitted: November 02, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Bulgaria, Hungary, United States
Conditions: Type 2 Diabetes Mellitus
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Study Description

Brief Summary

Primary Objective:

To demonstrate the non-inferiority of sotagliflozin dose 1 compared to glimepiride on HbA1c (glycosylated A1c) reduction in patients with T2D (type 2 diabetes) who have inadequate glycemic control with metformin.

Secondary Objectives:

To demonstrate the superiority of sotagliflozin dose 1 compared to glimepiride on change in body weight, SBP (systolic blood pressure) in patients with baseline SBP ≥130 mmHg, SBP in all patients, and proportion of patients with at least 1 documented symptomatic hypoglycemic event (≤70 mg/dL).

- To demonstrate the superiority of sotagliflozin dose 1 compared to placebo on change in HbA1c, body weight, SBP (systolic blood pressure) in patients with baseline SBP ≥130 mmHg, SBP in all patients.

- To demonstrate the superiority of sotagliflozin dose 2 compared to placebo on change in HbA1c.

- To demonstrate the non-inferiority of sotagliflozin dose 2 compared to glimepiride on change in HbA1c.

- To demonstrate the superiority of sotagliflozin dose 1 compared to glimepiride on change in HbA1c.

- To evaluate the safety and tolerability of sotagliflozin compared to glimepiride and placebo.

Detailed Description

Up to 58 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks, a 2-week single-blind placebo Run-in phase, a 52-week double-blind Treatment Period, and a 2-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: glimepiride
Other Names
Drug: metformin
Other Names
Drug: placebo
Other Names
Drug: placebo
Other Names
Phase 3

Tracking Information

First Submitted DateNovember 02, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateDecember 01, 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 hemoglobin A1c (for sotagliflozin dose1) [Time Frame: Baseline to Week 52]

    Absolute change from baseline to week 52 in hemoglobin A1c

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change in hemoglobin A1c (for sotagliflozin dose1) [Time Frame: Baseline to Week 26]

    Absolute change from baseline to week 26 in hemoglobin A1c

  • Change in body weight (for sotagliflozin dose1) [Time Frame: Baseline to Week 26]

    Absolute change from baseline to week 26 in body weight

  • Change in body weight (for sotagliflozin dose1) [Time Frame: Baseline to Week 52]

    Absolute change from baseline to week 52 in body weight

  • Change in SBP (systolic blood pressure) for patients with baseline SBP ≥130 mmHg (for sotagliflozin dose1) [Time Frame: Baseline to Week 12]

    Absolute change from baseline to week 12 in systolic blood pressure

  • Change in SBP for all patients (for sotagliflozin dose1) [Time Frame: Baseline to Week 12]

    Absolute change from baseline to week 12 in systolic blood pressure

  • At least one documented symptomatic hypoglycemic event (≤70 mg/dL) (for sotagliflozin dose1) [Time Frame: Baseline to Week 52]

    Proportion of participants with at least 1 documented symptomatic hypoglycemic event

  • Change in hemoglobin A1c (for sotagliflozin dose 2) [Time Frame: Baseline to Week 26]

    Absolute change from baseline to week 26 in hemoglobin A1c

  • Change in hemoglobin A1c (for sotagliflozin dose 2) [Time Frame: Baseline to Week 52]

    Absolute change from baseline to week 52 in hemoglobin A1c

  • Adverse events [Time Frame: Up to Week 52]

    Number of patients with adverse events

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Subjects With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy
Official TitleA 52-week Randomized, Double-blind, Double-dummy, Active and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Compared to Glimepiride or Placebo Added to Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin Monotherapy
Brief Summary

Primary Objective:

To demonstrate the non-inferiority of sotagliflozin dose 1 compared to glimepiride on HbA1c (glycosylated A1c) reduction in patients with T2D (type 2 diabetes) who have inadequate glycemic control with metformin.

Secondary Objectives:

To demonstrate the superiority of sotagliflozin dose 1 compared to glimepiride on change in body weight, SBP (systolic blood pressure) in patients with baseline SBP ≥130 mmHg, SBP in all patients, and proportion of patients with at least 1 documented symptomatic hypoglycemic event (≤70 mg/dL).

- To demonstrate the superiority of sotagliflozin dose 1 compared to placebo on change in HbA1c, body weight, SBP (systolic blood pressure) in patients with baseline SBP ≥130 mmHg, SBP in all patients.

- To demonstrate the superiority of sotagliflozin dose 2 compared to placebo on change in HbA1c.

- To demonstrate the non-inferiority of sotagliflozin dose 2 compared to glimepiride on change in HbA1c.

- To demonstrate the superiority of sotagliflozin dose 1 compared to glimepiride on change in HbA1c.

- To evaluate the safety and tolerability of sotagliflozin compared to glimepiride and placebo.

Detailed Description

Up to 58 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks, a 2-week single-blind placebo Run-in phase, a 52-week double-blind Treatment Period, and a 2-week post-treatment Follow-up period to collect safety information

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
930
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: glimepiride

Pharmaceutical form: capsule Route of administration: oral

Other Names
Drug: metformin

Pharmaceutical form: tablet 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 dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day

Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day

Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day

Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day

Study Arms
Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : glimepiride
Pharmaceutical form: capsule Route of administration: oral

Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: tablet Route of administration: oral

Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: capsule Route of administration: oral

Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: tablet Route of administration: oral

Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : sotagliflozin (SAR439954)
Pharmaceutical form: tablet Route of administration: oral

Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: capsule Route of administration: oral

Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: capsule Route of administration: oral

Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Pharmaceutical form: tablet Route of administration: oral

Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : sotagliflozin (SAR439954)
Pharmaceutical form: tablet Route of administration: oral

Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Arm Intervention/Treatment
Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : glimepiride
Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : metformin
Active Comparator Glimepiride
Two sotagliflozin-matching placebo tablets, and combination of 2 glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day
Drug : placebo
Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Placebo Comparator Placebo
Two sotagliflozin-matching placebo tablets and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin
Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : sotagliflozin (SAR439954)
Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin
Experimental Sotagliflozin dose 1
Sotagliflozin dose 1, given as two tablets, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : placebo
Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : sotagliflozin (SAR439954)
Experimental Sotagliflozin dose 2
Sotagliflozin dose 2, given as one tablet and one sotagliflozin-matching placebo tablet, and two glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day
Drug : metformin

Recruitment Information

Recruitment Status:Recruiting
Enrollment930
Completion DateMay 01, 2019
Eligibility Criteria: Inclusion criteria :
- Patients with Type 2 Diabetes (T2D) treated with metformin at a stable dose ≥1500 mg/day or maximum tolerated dose (documented) for at least 12 weeks prior to Screening Visit; in case of documented lack of tolerance, metformin dose <1500 mg/day is acceptable, and the dose should be stable for at least 12 weeks prior to Screening Visit.
- Patient has given written informed consent to participate in the study in accordance with local regulations.
Exclusion criteria:
- Age <18 years at the Screening Visit or - Type 1 diabetes mellitus.
- HbA1c <7.0% or HbA1c >10% at Screening.
- Fasting Plasma Glucose >15 mmol/L (>270 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.
- Body mass index ≤20 or >45 kg/m² at Screening.
- Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women.
- Women of childbearing potential (WOCBP) not willing to use highly effective 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 (see Appendix A) during the study.
- Previous use of any antidiabetic drug other than metformin within 12 weeks preceding the Screening Visit.
- Use of systemic glucocorticoids (excluding topical, or ophthalmic application, intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
- Previous insulin use >1 month (at any time, except for treatment of gestational diabetes).
- History of prior gastric surgical procedure, including gastric banding, or inflammatory bowel disease within 3 years prior to the Screening Visit.
- Difficulty swallowing such that the patient cannot take the Investigational Medicinal Product.
- 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 (DBP).
- History of hypertensive emergency within 12 weeks prior to Screening.
- Patients who have previously been randomized in any clinical trial of sotagliflozin/LX4211.
- Patients with severe renal disease as defined by an eGFR of <30 mL/min/1.73 m² at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation (or according to the renal function restrictions of metformin use defined in the local approved label).
- Patients with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease 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.
- 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).
- Patients who have taken other investigational drugs within 12 weeks or 5 half-lives from Screening whichever is longer.
- Patients who are unwilling to perform self-monitoring blood glucose (SMBG) and complete the patient diary as required per protocol.
- Patients with contraindication to glimepiride as per local labeling.
- Patients with contraindication to metformin as per local labeling.
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
Hungary
United States

Administrative Information

NCT Number:NCT03332771
Other Study ID Numbers
EFC14838
2016-001801-17
U1111-1190-7596
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