E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes. |
Diabete di tipo 2. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015491 |
E.1.2 | Term | Essential hypertension, unspecified |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012612 |
E.1.2 | Term | Diabetes mellitus non insulin-dep |
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 compare the reduction in office systolic BP and albuminuria (mean of three consecutive measurements in 24-hour urine collections) after 5 weeks Rostafuroxin therapy between two subsets of hypertensive type 2 diabetic patients with or without a pre-defined genetic profile (Profile 1) expected to be associated with adducin/ouabain dependent arterial hypertension and glomerular dysfunction. |
Paragonare la riduzione della pressione sistolica e dell’albuminuria (media di tre misurazioni consecutive nella raccolta urinaria delle 24 ore) dopo 5 settimane di trattamento con Rostafuroxina tra i due sottogruppi di pazienti ipertesi con diabete di tipo 2 con o senza il profilo genetico descritto nell’Appendice 1 al protocollo, associato ad ipertensione arteriosa e disfunzione glomerulare adducina/ouabaina dipendente. . |
|
E.2.2 | Secondary objectives of the trial |
• To compare between-group treatment-induced changes in the following parameters: - In office diastolic, mean and pulse BP; - Mean 24-hour systolic, diastolic, mean and pulse BP; - Day-time and night-time systolic, mean, diastolic and pulse BP; - Pulse wave velocity and other markers of vascular stiffness; - Glomerular filtration rate (as measured by the iohexol plasma clearance); - Albumin and IgG fractional clearance. • To explore the relationships between treatment-induced changes in office and 24-hour BP and concomitant changes in albuminuria in the study group as a whole and within each genotype group considered separately. • To assess treatment safety and tolerability (by evaluation of vital signs and routine laboratory parameters) in the study group as a whole and within each genotype group considered separately. • To explore the possibility that the response to Rostafuroxin is confined or present in the subset of patients carrying the profile 1 |
• Paragonare tra i due gruppi i cambiamenti indotti dal trattamento sui seguenti parametri: - Pressione arteriosa diastolica, media e curva di pressione in ambulatorio; - Pressione sistolica, diastolica, media e curva di pressione delle 24 ore; - Pressione sistolica, diastolica, media e curva di pressione delle 24 ore durante il giorno e durante la notte; - Frequenza del polso e altri marcatori di rigidita' vascolare; - Velocita' di filtrazione glomerulare (misurata come clearance plasmatica dello ioexolo); - Clearance frazionata dell’albumina e delle IgG. • Esplorare la relazione tra i cambiamenti indotti dai due trattamenti nella pressione in ambulatorio e delle 24 ore, e i cambiamenti nell’albuminuria nel gruppo in studio nel suo complesso e all’interno di ciascun genotipo considerato separatamente. • Esplorare la possibilita' che la risposta alla Rostafuroxina sia confinata al gruppo che presenta un certo genotipo o presente in entrambi i gruppi. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients; - Age > 18 years; - Hypertensive type 2 diabetes never-treated office systolic BP >135 mmHg in at least two consecutive visits one week apart (see Appendix 2); - High-normal, micro- or macro- albuminuria (urinary albumin excretion >10 mg/24 hours); - Normal kidney function (serum creatinine levels <1.4 mg/dl); - Capable of understanding the purpose of the study; - Written informed consent (signed and dated by the patient). |
- Uomini e donne di eta' superiore ai 18 anni; - Pazienti diabetici di tipo 2 ipertesi mai trattati con pressione sistolica in ambulatorio >135 mmHg in almeno due visite consecutive eseguite ad una settimana di distanza (vedi Appendix 2); - Escrezione urinaria di albumina >10 mg/24 hours; - Funzione renale normale (creatinina sierica <1.4 mg/dl); - Capacita' di comprendere gli obiettivi dello studio; - Consenso informato scritto (firmato e datato dal paziente). |
|
E.4 | Principal exclusion criteria |
- Concomitant treatment with drugs potentially affecting arterial BP, albuminuria or kidney function; - Secondary or grade 3 or more arterial hypertension (according to 2007 ESH/ESC Hypertension guidelines); - Non-diabetic renal disease, urinary tract infection, cardiovascular events over the last six months; - Any clinically relevant conditions that might affect study participation and/or study results; - Any contraindication to be exposed to Rostafuroxin; - Pregnancy or lactating; - Women of childbearing potential without following a scientifically accepted form of contraception; - Legal incapacity. |
- Trattamenti concomitanti con farmaci che possano avere effetto sulla pressione, sull’albuminuria o sulla funzione renale; - Ipertensione arteriosa secondaria, di grado 3 o superiore (in accordo con le Linee Guida ESH/ESC sull’ipertensione del 2007)4; - Malattia renale non-diabetica, infezioni delle vie urinarie, eventi cardiovascolari nei sei mesi precedenti l’inizio dello studio; - Qualsiasi condizione clinica rilevante che possa compromettere la partecipazione allo studio e/o i risultati dello studio stesso; - Qualsiasi controindicazione all’assunzione di Rostafuroxin; - Gravidanza o allattamento; - Donne potenzialmente fertili che non utilizzino metodi contraccettivi scientificamente approvati; - Incapacita' legale. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Office systolic BP - Albuminuria (mean of three consecutive measurements in 24-hour urine collections) |
- Pressione sistolica misurata in ambulatorio - Albuminuria (media di tre misurazioni consecutive sulla raccolta delle 24 ore) |
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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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |