| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067585 |
| E.1.2 | Term | Type 2 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
- 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 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Patients with Type 2 Diabetes 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. |
|
| E.4 | Principal exclusion criteria |
-Age <18 years at the Screening Visit or <legal age of majority, whichever is greater.
-Type 1 diabetes mellitus.
-HbA1c <7.0% or HbA1c >10% at Screening.
-Fasting Plasma Glucose (FPG) >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 a selective SGLT2 inhibitor (e.g., canagliflozin, dapagliflozin or empagliflozin) within 3 months prior to 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 IMP.
-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 unwilling or unable to perform self-monitoring blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol.
-Patients with contraindication to glimepiride as per local labeling.
-Patients with contraindication to metformin as per local labeling. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in hemoglobin A1c (for sotagliflozin dose1): Absolute change from baseline to week 52 in hemoglobin A1c |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1) Change in hemoglobin A1c (for sotagliflozin dose1): Absolute change from baseline to week 26 in hemoglobin A1c
2) Change in body weight (for sotagliflozin dose1): Absolute change from baseline to week 26 in body weight
3) Change in body weight (for sotagliflozin dose1): Absolute change from baseline to week 52 in body weight
4) Change in SBP (systolic blood pressure) for patients with baseline SBP ≥130 mmHg (for sotagliflozin dose1): Absolute change from baseline to week 12 in systolic blood pressure
5) Change in SBP for all patients (for sotagliflozin dose1): Absolute change from baseline to week 12 in systolic blood pressure
6) At least one documented symptomatic hypoglycemic event (≤70 mg/dL) (for sotagliflozin dose1): Proportion of participants with at least 1 documented symptomatic hypoglycemic event
7) Change in hemoglobin A1c (for sotagliflozin dose 2): Absolute change from baseline to week 26 in hemoglobin A1c
8) Change in hemoglobin A1c (for sotagliflozin dose 2): Absolute change from baseline to week 52 in hemoglobin A1c
9) Adverse events: Number of patients with adverse events |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1), 2) and 7) Baseline to Week 26
3), 6) and 8) Baseline to Week 52
4) and 5) Baseline to Week 12
9) Up to Week 52 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient-reported outcomes |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Hungary |
| Slovakia |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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