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 |
pazienti affetti da diabete mellito di tipo 2 e scompenso cardiaco |
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E.1.1.1 | Medical condition in easily understood language |
diabetic patients with heart failure |
pazienti diabetici e con scompenso cardiaco |
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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 | HLT |
E.1.2 | Classification code | 10012654 |
E.1.2 | Term | Diabetic complications cardiovascular |
E.1.2 | System Organ Class | 100000004860 |
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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 |
Determinare il segnale dose-risposta e valutare la relazione dose-risposta di tre regimi di dosaggio di LIK066 tramite la misurazione della variazione rispetto al basale di NT-proBNP rispetto a placebo, dopo 12 settimane di trattamento in pazienti affetti da T2DM e HF. |
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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. Valutare l’effetto di tutte le dosi di LIK066 rispetto a placebo a 12 settimane e a 36 settimane su: ¿ Variazione rispetto al basale dell’emoglobina glicata (HbA1c) ¿ Variazione rispetto al basale della glicemia a digiuno (Fasting Plasma Glucose – FPG) ¿ Variazione rispetto al basale del peso ¿ Variazione rispetto al basale della composizione corporea (bio-impedenza in tutti i pazienti laddove appropriato e assorbimetria a raggi x a doppia energia [Dual-energy X-ray Absorptiometry – DXA] in un sottogruppo di pazienti) ¿ Variazione rispetto al basale di pressione sistolica (Systolic Blood Pressure - SBP) e diastolica (Diastolic Blood Pressure - DBP) in posizione seduta ¿ Variazione rispetto al basale del profilo lipidico a digiuno e della proteina-C reattiva ad alta sensibilità (high-sensitivity C-reactive Protein – hsCRP) ¿ Variazione rispetto al basale dell’escrezione di glucosio e sodio urinario nelle 24 ore, in un sottogruppo di pazienti ¿per favore ved. prot/sinossi in italiano |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• BMI = 22kg/m^2 • Type 2 diabetes with HbA1c between 6.5% and 10.0% • Documented symptomatic chronic heart failure (NYHA II-IV) • Plasma NT-proBNP > 300pg/ml • eGFR = 45ml/min/1.73m^2 (calculated by MDRD) |
¿ Pazienti ambulatoriali di sesso maschile o femminile di età = 18 anni ¿ BMI = 22kg/m2 ¿ Diabete di tipo 2 con HbA1c tra 6.5% e 10.0% ¿ Scompenso cardiaco cronico sintomatico documentato (NYHA II-IV) ¿ NT-proBNP plasmatico > 300pg/ml ¿ I pazienti in trattamento con ACEi, ARBs, MRAs, ARNi e/o ß-bloccanti devono essere in trattamento con dosi stabili di questi farmaci ¿ eGFR = 45ml/min/1.73m2 (calcolato tramite MDRD) |
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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 • History of ketoacidosis, lactic acidosis, or hyperosmolar coma • 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 |
¿ Diabete di tipo 1, diabete monogenico, diabete risultante da danno pancreatico o forme secondarie di diabete ¿ Chetoacidosi, acidosi lattica, o coma iperosmolare verificatasi prima della randomizzazione ¿ Infezione genitale sintomatica o UTI nelle 4 settimane precedenti lo screening ¿ Infarto miocardico, ictus, intervento chirurgico per malattia cardiaca, intervento coronarico percutaneo nei 3 mesi precedenti la randomizzazione ¿ Angina instabile nei 3 mesi precedenti lo screening ¿ Scompenso cardiaco destro isolato dovuto a malattia polmonare ¿ Pazienti con pressione sistolica media in posizione seduta =100mmHg, alla randomizzazione ¿ Storia di amputazione degli arti inferiori (inclusa l’amputazione delle dita) verificatasi prima della randomizzazione ¿ Ulcera diabetica del piede allo screening, o prima della randomizzazione • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in NTproBNP at week 12 |
cambiamento dal basale alla settimana 12 nel NT-proBNP |
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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 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 |
- Cambiamento dal basale (BL) in HbA1c - Cambiamento dal BL nella glicemia a digiuno - Cambiamento dal BL nel peso corporeo - Cambiamento dal BL nella composizione corporea - Cambiamento dal BL in sitting SBP and DBP - Cambiamento dal BL in the fasting lipid profile and hsCRP - Cambiamento dal BL in 24h urinary glucose and sodium excretion - Cambiamento dal BL in left atrial size and volume assessed by echocardiography - Cambiamento dal BL in NYHA class - Cambiamento dal BL in NT-proBNP - 24h urinary calcium and phosphate excretion - bone mineral density |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, week 12, week 36 |
basale, settimana 12, settimana 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 | 9 |
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 | Information not present in EudraCT |
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 |
Canada |
Guatemala |
Korea, Republic of |
Mexico |
Singapore |
South Africa |
Taiwan |
United States |
Austria |
Belgium |
Bulgaria |
Denmark |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Slovakia |
Spain |
United Kingdom |
Argentina |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |