E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus
Chronic kidney disease stage 4 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus
Chronic kidney disease stage 4 |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076411 |
E.1.2 | Term | Chronic kidney disease stage 4 |
E.1.2 | System Organ Class | 100000004857 |
|
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 |
|
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 superiority of sotagliflozin dose 1 versus placebo with respect to hemoglobin A1c (HbA1c) reduction in patients with Type 2 diabetes who have inadequate glycemic control and severe renal impairment |
|
E.2.2 | Secondary objectives of the trial |
-To assess the effects of sotagliflozin dose 2 versus placebo based on change from baseline in HbA1c
-To assess the effects of sotagloflozin doses 1 and 2 versus placebo
-To evaluate the safety of sotagliflozin doses 1 and 2 versus placebo
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with T2D (drug-naïve or on antidiabetic therapy) and documented severe renal insufficiency - CKD4 - defined by an eGFR equation (based on the 4 variable modification of diet in renal disease [MDRD] equation) of ≥15 and <30 mL/min/1.73 m2.
-Signed written informed consent to participate in the study in accordance with local regulations. |
|
E.4 | Principal exclusion criteria |
-At the time of screening, age <18 years.
-Hemoglobin A1c (HbA1c) <7% or >11%.
-Type 1 diabetes.
-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 during the study.
-Treatment with an SGLT2 inhbitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months.
-Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy, will
preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
-Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in HbA1c: Change from Baseline at Week 26 in HbA1c comparing sotagliflozin dose 2 versus placebo
- Change in Fasting Plasma Glucose (FPG): Change from Baseline at Week 26 in FPG (doses 1 and 2)
- Change in Systolic Blood Pressure (SBP) for patients with SBP ≥130 mmHg: Change from Baseline in SBP at Week 12 for patients with SBP greater than or equal to 130 mmHg (doses 1 and 2)
- Change in SBP: Change from Baseline at Week 12 in SBP in all patients (dose 1 and dose 2)
- Change in body weight: Change from Baseline at Week 26 in Body weight (doses 1 and 2)
- Change in urinary albumin-to-creatinine ratio (UACR): Percentage change in the UACR from Baseline to Week 26 for patients with a UACR > 30 mg/g at baseline (doses 1 and 2)
- Patients with HbA1c < 6.5%: Percentage of patients with HbA1c < 6.5% at Week 26 (doses 1 and 2)
- Patients with HbA1c < 7.0%: Percentage of patients with HbA1c < 7.0% at Week 26 (doses 1 and 2)
- Adverse events: Number of patients with adverse events up to week 52 (doses 1 and 2) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Change in HbA1c : Baseline to Week 26
- Change in Fasting Plasma Glucose (FPG) : Baseline to Week 26
- Change in Systolic Blood Pressure (SBP) for patients with SBP ≥130 mmHg : Baseline to Week 12
- Change in SBP : Baseline to Week 12
- Change in body weight : Baseline to Week 26
- Change in urinary albumin-to-creatinine ratio (UACR) : Baseline to Week 26
- Patients with HbA1c < 6.5% : Week 26
- Patients with HbA1c < 7.0% : Week 26
- Adverse events : Week 52 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Argentina |
Brazil |
Colombia |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Ukraine |
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
|
Last Subject Last Visist (LSLV) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 25 |
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 | 2 |