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 |
Diabetes mellitus de tipo 2 Insuficiencia renal grave (estadío 4) |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus Chronic kidney disease stage 4 |
Diabetes mellitus de tipo 2 Insuficiencia renal grave (estadío 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 | 20.0 |
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 | 100000070575 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 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 |
Demostrar la superioridad de la sotagliflozina a una dosis de 400 mg frente al placebo para reducir la hemoglobina A1c (HbA1c) en pacientes con diabetes mellitus de tipo 2 (DMT2) que tienen una insuficiencia renal grave con un control inadecuado de la glucemia. |
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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 |
Valorar los efectos de la sotagliflozina a una dosis de 400 mg frente a los del placebo en función del cambio de la HbA1c. Valorar los efectos de la sotagliflozina a una dosis de 200 mg y 400 mg frente a los del placebo Evaluar la seguridad de sotagliflozina a una dosis de 200 mg y 400 mg frente a los del placebo |
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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. |
- Pacientes con DMT2 (sin tratamiento previo o con un tratamiento antidiabético) e insuficiencia renal grave documentada –insuficiencia renal crónica (IRC) de estadio 4, definida de acuerdo con una ecuación de la TFGe (basada en la MDRD de cuatro variables) de ≥15 y <30 ml/min/1,73 m2. - Consentimiento informado por escrito firmado para participar en el estudio conforme a la normativa local. |
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E.4 | Principal exclusion criteria |
-At the time of screening, age <18 years. -Hemoglobin A1c (HbA1c) <7% or >11%. -Type 1 diabetes. -Women who could become pregnant. -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. |
- Tener menos de18 años o ser menor de edad en el momento de la selección - Hemoglobina A1c (HbA1c) inferior a 7% o superior a 11%. - Diabetes mellitus de tipo 1 - Mujeres fértiles que no están de acuerdo en utilizar métodos anticonceptivos de gran eficacia o que no desean o no pueden someterse a una prueba de embarazo durante el estudio. - Tomar un inhibidor selectivo del cotransportador de sodio-glucosa tipo 2 (SGLT2) como, por ejemplo, canagliflozina, dapagliflozina o empagliflozina, en los 12 meses previos al inicio del estudio. - Tensión arterial alta no controlada, anemia grave, enfermedad cardiovascular grave (p.ej. una insuficiencia cardiaca congestiva de clase IV), un tumor maligno activo u otras enfermedades sistémicas graves con una esperanza de vida corta que, a juicio del investigador. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c |
Cambio de la HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to Week 26 |
Desde el inicio del estudio hasta la semana 26 |
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E.5.2 | Secondary end point(s) |
- Change in HbA1c - Change in Fasting Plasma Glucose (FPG) - Change in Systolic Blood Pressure (SBP) for patients with SBP ≥130 mmHg - Change in SBP - Change in body weight - Change in urinary albumin-to-creatinine ratio (UACR) - Patients with HbA1c < 6.5% - Patients with HbA1c < 7.0% - Adverse events |
- Cambio de la HbA1c - Cambio en la glucemia plasmática en ayunas (GPA) - Cambio de la tensión arterial sistólica (TAS) para los pacientes con una TAS basal de ≥130 mmHg - Cambio de la tensión arterial sistólica TAS. - Cambio en el peso corporal - Cambio porcentual del cociente albúmina/creatinina (CAC) - Pacientes con HbA1c inferior a 6.5% - Pacientes con HbA1c inferior a 7.0% - Acontecimientos adversos |
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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 |
- Cambio de la HbA1c: Desde el inicio del estudio hasta la semana 26 - Cambio en la glucemia plasmática en ayunas (GPA): Desde el inicio del estudio hasta la semana 26 - Cambio de la tensión arterial sistólica (TAS) para los pacientes con una TAS basal de ≥130 mmHg: Desde el inicio del estudio hasta la semana 12 - Cambio de la tensión arterial sistólica TAS: Desde el inicio del estudio hasta la semana 12 - Cambio en el peso corporal:Desde el inicio del estudio hasta la semana 26 - Cambio porcentual del cociente albúmina/creatinina (CAC):Desde el inicio del estudio hasta la semana 26 - Pacientes con HbA1c inferior a 6.5%: Semana 26 - Pacientes con HbA1c inferior a 7.0%: Semana 26 - Acontecimientos adversos: Semana 26 |
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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 | 8 |
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 |
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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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Last Subject Last Visist (LSLV) |
Última visita del último paciente (LPLV) |
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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 | 2 |
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 | 2 |