E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Essential hypertension |
Ipertensione essenziale |
|
E.1.1.1 | Medical condition in easily understood language |
High blood pressure |
Pressione sanguigna alta |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015488 |
E.1.2 | Term | Essential hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular 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 evaluate the efficacy of oral aliskiren 300 mg given once daily in reduction of mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of 8 week treatment under light meal (fed) versus fasted conditions in patients with mild to moderate hypertension. |
Valutare l’efficacia di aliskiren 300 mg nel ridurre la pressione arteriosa sistolica ambulatoria media nelle 24 ore (mean 24 hour ambulatory Systolic Blood Pressure - maSBP) dal basale alla fine di un periodo di trattamento di 8 settimane, somministrato una volta al giorno per via orale con un pasto leggero rispetto alla somministrazione a digiuno in pazienti con ipertensione da lieve a moderata. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of oral aliskiren 300 mg in reduction of mean 24 hour maDBP from baseline to end of 8 week treatment under light meal versus fasted conditions in patients with mild to moderate hypertension; To evaluate the efficacy of oral aliskiren in reduction of the mean change of msSBP and msDBP; To evaluate the effect of a light meal versus fasted condition on aliskiren pharmacokinetics and PRA; To evaluate the proportion of patients achieving blood pressure control; To assess the proportion of patients achieving a successful response in SBP reduction; To evaluate the safety and tolerability of aliskiren under a light meal and fasted conditions in patients with mild to moderate hypertension. |
- Valutare l’efficacia di aliskiren 300 mg nel ridurre la pressione arteriosa diastolica ambulatoriale (maDBP) media nelle 24 ore dal basale alla fine di un periodo di trattamento di 8 settimane, somministrato una volta al giorno per via orale con un pasto leggero rispetto alla somministrazione a digiuno in pazienti con ipertensione da lieve a moderata; -Valutare l'efficacia di aliskiren 300 mg nel ridurre la variazione media di msSBP and msDBP; -Valutare l'effetto di un pasto leggero rispetto a condizioni di digiuno sulla farmacocinetica e PRA di aliskiren 300 mg; -Valutare la proporzione di pazienti che hanno ottenuto il controllo della pressione arteriosa; -Valutare la proporzione di pazienti che hanno ottenuto una risposta positiva nel ridurre la SBP |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed; 2. Male or female outpatients age ≥ 18 years old; 3. Patients with essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy); 4. Patients must have an office BP ≥ 140/90 mmHg and < 180/110 mmHg at the randomization visit and the preceding visit; 5. Patients must have an absolute difference of ≤ 10 mmHg in both their msSBP and in their msDBP between the randomization visit and the preceding visit; 6. Ability to communicate and comply with all study requirements. |
- Pazienti ambulatoriali di sesso maschile o femminile e di età ≥ 18 anni; - Pazienti con ipertensione essenziale, non trattati o che attualmente assumono una terapia antipertensiva (in monoterapia o in combinazione); - Pazienti con valori di pressione arteriosa misurati in ambulatorio ≥ 140/90 mmHg e < 180/110mmHg alla visita di randomizzazione e alla visita precedente; - Pazienti con una differenza assoluta ≤ 10 mmHg sia nella msSBP che nella msDBP tra la visita di randomizzazione e la visita precedente. Per maggiori dettagli consultare il paragrafo 4.1 del protocollo originale. |
|
E.4 | Principal exclusion criteria |
1. Malignant hypertension or severe hypertension (grade 3 of WHO classification; msSBP ≥180 mmHg or msDBP ≥110 mmHg); 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases; 3. History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, druginduced hypertension, pheochromocytoma and polycystic kidney disease (PKD); 4. History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneaous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease with in 6 months of Visit 1; 5. Type 1 or Type 2 diabetes mellitus with fasting glycosylated hemoglobin (HbA1c) > 8%; 6. Clinically significant valvular heart disease; 7. Previous or current diagnosis of congestive heart failure NYHA Class II to IV; 8. Second or third degree heart block without a pacemaker, potentially life threatening arrhythmia, symptomatic arrhythmia, or family history of torsade de pointe; 9. Evidence of hepatic disease as determined by one of the following: ALT or AST values ≥ 3 x ULN at Visit 1, or a history of liver cirrhosis, hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt; 10. Evidence of renal impairment as determined by one of the following: serum creatinine >1.5 x ULN or eGFR < 30 ml/min/1.73m2 at Visit 1, a history of dialysis, or a history of nephrotic syndrome; 11. Other significant laboratory findings such as anemia defined as Hb < 10 g/dL, serum sodium value < 132 mmol/L or serum potassium values <3.5 mmol/L or >5.3 mmol/L at Visit 1; 12. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of aliskiren, including but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active, or active inflammatory bowel syndrome within 12 months prior to Visit 1, regarded as clinically meaningful by the investigator; 13. Patients with active gastritis, active peptic ulcer, gastro-esophageal reflux requiring medical therapy, gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator.For a complete list of exclusion criteria please refer to the study protocol. |
- Ipertensione maligna o ipertensione severa (grado 3 secondo la classificazione WHO); msSBP ≥180 mmHg o msDBP ≥110 mmHg; - Storia o evidenza di una forma di ipertensione secondaria, come ipertensione parenchimale renale, ipertensione renovascolare, coartazione dell’aorta, iperaldosteronismo secondario, malattia di Cushing, ipertensione farmaco indotta, stenosi dell’arteria renale unilaterale o bilaterale, feocromocitoma, malattia del rene policistico; - Diabete mellito di tipo 1 o 2 con emoglobina glicosilata (HbA1c) a digiuno > 8%; - Qualsiasi condizione medica o chirurgica che possa alterare in modo significativo l’assorbimento, la distribuzione, il metabolismo o l’escrezione di aliskiren, compreso, a titolo esemplificativo, uno qualsiasi dei seguenti: storia di chirurgia maggiore del tratto gastrointestinale come gastrectomia, gastroenterostomia, resezione intestinale, bypass gastrico, stapling gastrico o bendaggio gastrico, sindrome intestinale infiammatoria attualmente attiva, o attiva nei 12 mesi precedenti la Visita 1, clinicamente significativa a giudizio dello sperimentatore. Per maggiori dettagli consultare il paragrafo 4.2 del protocollo originale. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
24 hours mean systolic ambulatory blood pressure |
Pressione arteriosa sistolica ambulatoria media nelle 24 ore |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks of treatment |
Dopo 8 settimane di trattamento |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Canada |
Taiwan |
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
|
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |