E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus
Chronic kidney disease stage 3 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus
Chronic kidney disease stage 3 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 |
|
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 | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
E.1.2 | System Organ Class | 100000004857 |
|
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 and 2 versus placebo on HbA1c reduction in patients with Type 2 diabetes who have inadequate glycemic control and moderate renal impairment |
|
E.2.2 | Secondary objectives of the trial |
-To assess the effects of sotagliflozin dose 1 and 2 versus placebo with respect to additional measures of glycemic control, blood pressure, and body weight
-To evaluate the safety of sotagliflozin dose 1 and dose 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 moderate renal insufficiency defined by an eGFR (based on the 4 variable Modification of Diet in Renal Disease [MDRD] equation) of ≥30 and <60 mL/min/1.73 m2 (CKD 3A, 3B).
-Patient has given written informed consent to participate in the study in accordance with local regulations. |
|
E.4 | Principal exclusion criteria |
-Hemoglobin A1c (HbA1c) of <7.0% or >11.0%.
-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.
-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 or patients with short life expectancy that, according to the Investigator, 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c for dose 1 and dose 2 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Change in Fasting Plasma Glucose (FPG) (doses 1 and 2)
2. Change in Systolic Blood Pressure (SBP) for patients with SBP ≥130 mmHg (doses 1 and 2)
3. Change in Systolic Blood Pressure (SBP) (doses 1 and 2)
4. Change in body weight (doses 1 and 2)
5. Percentage change in UACR for patients with UACR > 30 mg/g (doses 1 and 2)
6. Proportion of patients with HbA1c < 6.5% (doses 1 and 2)
7. Proportion of patients with HbA1c < 7.0% (doses 1 and 2)
8. Proportion of patients with adverse events over the study period (doses 1 and 2) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Change in Fasting Plasma Glucose (FPG) : Baseline to Week 26
2. Change in Systolic Blood Pressure (SBP) for patients with SBP ≥130 mmHg : Baseline to Week 12
3. Change in Systolic Blood Pressure (SBP) : Baseline to Week 12
4. Change in body weight : Baseline to Week 26
5. Change in urinary albumin-to-creatinine ratio (UACR) : Baseline to Week 26
6. Patients with HbA1c <6.5% : Week 26
7. Patients with HbA1c <7.0% : Week 26
8. Patients with adverse events : Week 56 |
|
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 | 64 |
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 |
Canada |
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) |
|
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 |