E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with type 2 diabetes mellitus and heart failure |
pacientes con diabetes mellitus tipo 2 con insuficiencia cardíaca |
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E.1.1.1 | Medical condition in easily understood language |
diabetic patients with heart failure |
pacientes diabéticos con insuficiencia cardiaca |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 assess the dose-response relationship of three dose regimens of LIK066 as measured by the change from baseline in NT-proBNP relative to placebo after 12 weeks of treatment in T2DM patients with HF |
Evaluar la relación dosis-respuesta de tres regímenes de dosis de LIK066 medida por el cambio respecto al valor basal (BL) en NT-proBNP comparado frente al placebo después de 12 semanas de tratamiento en pacientes con DMT2 con IC |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of all LIK066 doses vs placebo or empagliflozin at 12 weeks and 36 weeks on: - Change from baseline (BL) in HbA1c - Change from BL in fasting plasma glucose - Change from BL in body weight - Change from BL in body composition - Change from BL in sitting SBP and DBP - Change from BL in 24h urinary glucose and sodium excretion - Change from BL in the fasting lipid profile and hsCRP 2. Change from BL in left atrial size and volume assessed by echocardiography relative to placebo after 12 and 36 weeks of treatment 3. Change from BL in NYHA class relative to placebo after 12 and 36 weeks of treatment 4. To evaluate the change from BL to 36 weeks in all LIK066 doses vs placebo on NT-proBNP. 5. To evaluate bone mineral density and 24h urinary calcium and phosphate excretion |
1. Evaluar el efecto de todas las dosis de LIK066 vs placebo a las 12 y 36 semanas en el: -Cambio respecto al valor BL en la HbA1c -Cambio respecto al valor BL en la glucosa plasmática en ayunas -Cambio respecto al valor BL en el peso -Cambio respecto al valor BL en la composición corporal -Cambio respecto al valor BL en la PAS y PAD en sedestación -Cambio respecto al valor BL en la excreción de glucosa y sodio en orina de 24h -Cambio respecto al valor BL en el perfil lipídico en ayunas y hsCRP 2.Cambio respecto al valor BL en el tamaño y volumen de la aurícula izquierda evaluados por ecocardiografía respecto al placebo despues de la semana 12 y 36 de tratamiento. 3. Cambio respecto al valor BL en la clase de la NYHA respecto al placebo despues de la semana 12 y 36 de tratamiento. 4. Evaluar el cambio desde la BL hasta las 36 semanas en todas las dosis de LIK066 vs placebo en NT-proBNP. 5. Evaluar la densidad mineral ósea y la excreción de calcio y fosfato en orina de 24h |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There are two sub-studies which are part of the main study protocol CLIK066B2204. - Sub-study 1: In about 25% of patients at participating sites, a DXA scan to assess body composition will be performed as indicated in the study protocol; in addition bone mineral density will be assessed, also as noted in the protocol. - Sub-study 2: UGE, albumin, creatinine and sodium excretion will be measured from a 24h urine collection from about 25% of randomized patients as indicated in the study protocol; bone biomarkers and renal biomarkers will be measured from the same urine collection and serum samples. |
Hay dos sub –estudios que forman parte del protocolo del estudio CLIK066B2204. -Sub.estudio 1; A aproximadamente un 25% de los pacientes en los centros participantes se les realizará una exploración DXA para evaluar la composición corporal tal y como indica el protocolo, además se evaluará la densidad mineral ósea, también indicada en el protocolo -Sub-estudio 2; Se medirán la EGO, la excreción de albúmina, creatinina y sodio en una muestra de orina de 24h de aproximadamente el 25% de los pacientes aleatorizados en las visitas que se indican en protocolo; Se medirán biomarcadores óseos y biomarcadores renales utilizando la misma recogida de orina |
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E.3 | Principal inclusion criteria |
• BMI > = 22kg/m^2 • Type 2 diabetes with HbA1c between 7.0% and 10.0% • Documented symptomatic chronic heart failure (NYHA II-IV) • Plasma NT-proBNP > 400pg/ml • eGFR > = 45ml/min/1.73m^2 (calculated by MDRD) |
-IMC > = 22kg/m2 -Diabetes tipo 2 con HbA1c entre 7,0% y 10,0% -Insuficiencia cardíaca crónica sintomática documentada (NYHA II-IV) -NT-proBNP en plasma > 400pg/ml -TFGe > = 45ml/min/1,73m2 (calculada con MDRD) |
|
E.4 | Principal exclusion criteria |
• Pregnant or nursing (lactating) women • Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes • Ketoacidosis, lactic acidosis, or hyperosmolar coma within 6 months of screening • Symptomatic genital infection or UTI within 4 weeks of screening • Myocardial infarction, stroke, surgery for heart disease, percutaneous coronary intervention within 3 months of screening • Unstable angina within 3 months of screening • Isolated right HF due to pulmonary disease • Patients with a mean sitting systolic blood pressure <= 100mmHg, at randomization |
- Mujeres embarazadas o en period de lactancia -Diabetes tipo 1, diabetes monogénica, diabetes como consecuencia de una lesión pancreática, o formas secundarias de diabetes -Cetoacidosis, acidosis láctica, o coma hiperosmolar dentro de los 6 meses anteriores a la selección -Infección genital sintomática o ITU dentro de las 4 semanas anteriores a la selección -Infarto de miocardio, ictus, cirugía debido a cardiopatía, intervención coronaria percutánea dentro de los 3 meses anteriores a la selección -Angina inestable dentro de los 3 meses anteriores a la selección -IC derecha aislada debido a enfermedad pulmonary -Pacientes con presión arterial sistólica en sedestación media <= 100 mmHg, en la aleatorización |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in NTproBNP at week 12 |
Cambio respect a la basal en NTproBNP en la semana 12 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, week 12 |
basal, semana 12 |
|
E.5.2 | Secondary end point(s) |
- Change from baseline (BL) in HbA1c - Change from BL in fasting plasma glucose - Change from BL in body weight - Change from BL in body composition - Change from BL in sitting SBP and DBP - Change from BL in the fasting lipid profile and hsCRP - Change from BL in 24h urinary glucose and sodium excretion - Change from BL in left atrial size and volume assessed by echocardiography - Change from BL in NYHA class - Change from BL in NT-proBNP - 24h urinary calcium and phosphate excretion - bone mineral density |
-Cambio respecto al valor BL en HbA1c -Cambio respecto al valor BL en la GPA -Cambio respecto al valor BL en el peso -Cambio respecto al valor BL en la composición corporal -Cambio respecto al valor BL en la PAS y PAD en sedestación -Cambio respecto al valor BL en el perfil lipídico en ayunas y hsCRP -Cambio respecto al valor BL en la excreción de glucosa y sodio en orina -Cambio respecto al valor BL en el tamaño y volumen de la aurícula izquierda evaluados por ecocardiografía -Cambio respecto al valor BL en la clase de la NYHA -Cambio respecto al valor BL en NT-proBNP -Excreción de calcio y fosfato en orina de 24h -Densidad mineral ósea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, week 12, week 36 |
Basal, semana 12, semana 36 |
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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 | No |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Denmark |
Germany |
Guatemala |
Hungary |
Ireland |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Norway |
Poland |
Singapore |
South Africa |
Spain |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
LVLS |
Última paciente última visita |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |