| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| elderly Hypertensive patients |
| pazienti anziani con ipertensione |
|
| E.1.1.1 | Medical condition in easily understood language |
| elderly Hypertensive patients |
| pazienti anziani ipertesi |
|
| 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 | 10020772 |
| E.1.2 | Term | Hypertension |
| 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 | 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 demonstrate superiority of an LCZ696 regimen compared to an olmesartan regimen, as measured by change from baseline in mean Central Aortic Systolic Blood Pressure (CASP) after 12 weeks of treatment in elderly patients with essential hypertension. |
| Obiettivo Primario: dimostrare la superiorità di un regime di trattamento con LCZ696 rispetto ad un regime di trattamento con olmesartan, misurata tramite la variazione rispetto al basale della pressione sistolica aortica centrale (CASP) dopo 12 settimane di trattamento in pazienti anziani con ipertensione essenziale. |
|
| E.2.2 | Secondary objectives of the trial |
| Key Secondary Objective: To demonstrate superiority of an LCZ696 regimen compared to an olmesartan regimen, as measured by change from baseline in mean Central Pulse Pressure (CPP) after 12 weeks of treatment. |
| Obiettivo Secondario Principale: dimostrare la superiorità di un regime di trattamento con LCZ696 rispetto ad un regime di trattamento con olmesartan, misurata tramite la variazione rispetto al basale della pressione differenziale centrale (Central Pulse Pressure – CPP) dopo 12 settimane di terapia. |
|
| 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 |
PHARMACOGENETIC:
Vers:original
Date:2012/07/02
Title:A randomized, double-blind, active-controlled, multicenter, 52-week study to evaluate the safety and efficacy of an LCZ696 regimen on arterial stiffness through assessment of central blood pressure in elderly patients with essential hypertension
Objectives:n.a.
|
FARMACOGENETICA:
Vers:original
Data:2012/07/02
Titolo:Studio multicentrico, randomizzato, in doppio cieco, verso controllo attivo, della durata di 52 settimane per valutare la sicurezza e l’efficacia di un regime di trattamento con LCZ696 sulla rigidità arteriosa tramite la valutazione della pressione arteriosa centrale in pazienti anziani affetti da ipertensione essenziale.
Obiettivi:Vi informiamo che, anche se il protocollo non prevede un sottostudio formalmente definito (ovvero strutturato con un protocollo specifico) ma una indagine complementare opzionale, la stessa viene classificata come sottostudio e quindi formalizzata nell’apposita sezione del CTA Form. Di seguito il dettaglio: • Indagine di farmacogenetica, a cui parteciperanno tutti i centri italiani coinvolti nello studio. L’eventuale non accettazione di tale sottostudio da parte del Comitato Etico e/o da parte del paziente non comprometterà in alcun modo la partecipazione allo studio principale.
|
|
| E.3 | Principal inclusion criteria |
| • Written informed consent must be obtained before any assessment is performed • Male and female patients ≥ 60 years of age. • Patients with essential hypertension, untreated or currently taking antihypertensive therapy. • Untreated patients must have an office msSBP ≥150 mmHg and <180 mmHg at Visit 101 and Visit 201 if they are newly diagnosed or have not been treated with antihypertensive drugs for the 4 weeks prior to Visit 1. • Treated patients must have an office msSBP ≥140 mmHg and <180 mmHg at Visit 102 (or Visit 103) and msSBP ≥150 mmHg and <180 mmHg at Visit 201 if they have been treated with antihypertensive drugs for the 4 weeks prior to Visit 1. • All patients must have pulse pressure >60 mmHg at Visit 201. Pulse pressure is defined as msSBP- msDBP. • Patients must have a difference in msSBP of +/-15 mmHg betweenv Visit 201 (randomization) and the visit immediately prior to Visit 201. • Patients with the ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥80% compliance rate) during the run-in epoch (Epoch 2). |
| Consenso informato scritto ottenuto prima dell’effettuazione di qualsiasi valutazione. Pazienti di sesso maschile e femminile di età ≥ 60 anni. Pazienti affetti da ipertensione essenziale, non trattati o attualmente in trattamento con terapia antiipertensiva. I pazienti non trattati devono avere una misurazione effettuata in ospedale di msSBP ≥150 mmHg e <180 mmHg alla Visita 101 e alla Visita 201 se sono pazienti di nuova diagnosi o se non sono stati trattati con farmaci antiipertensivi nelle 4 settimane precedenti la Visita 1. I pazienti trattati devono avere una misurazione effettuata in ospedale di msSBP ≥140 mmHg e <180 mmHg alla Visita 102 (o alla Visita 103) e msSBP ≥150 mmHg e <180 mmHg alla Visita 201 se sono stati trattati con farmaci antiipertensivi nelle 4 settimane precedenti la Visita 1. Tutti pazienti devono presentare una pressione differenziale > 60 mmHg alla Visita 201. La pressione differenziale è definita come msSBP- msDBP. I pazienti devono presentare una differenza nella msSBP di +/-15 mmHg tra la Visita 201 (randomizzazione) e la visita immediatamente precedente alla Visita 201. |
|
| E.4 | Principal exclusion criteria |
| Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥180 mmHg). History of angioedema, drug-related or otherwise. 4. History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension. 5. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke. 6. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1. 7. Current angina pectoris requiring pharmacological therapy (other than patients on a stable dose of oral or topical nitrates). 8. Type 1 or Type 2 diabetes mellitus not well controlled based on the investigator's clinical judgment. Patients currently being treated for diabetes mellitus should be on stable dose of anti-diabetic medication for at least 4 weeks prior to Visit 1. 9. Previous or current diagnosis of heart failure (NYHA Class II-IV). 10. Clinically significant valvular heart disease at Visit 1. 11. History of atrial fibrillation or atrial flutter during the 3 months prior to Visit 1, or active atrial fibrillation or atrial flutter on the ECG at Visit 101. 12. History or current diagnosis of the following cardiac abnormalities: • Second or third degree AV block without a pacemaker. • History of familial long QT syndrome or family history of torsade de pointe.... |
| Ipertensione maligna o severa (grado 3 della classificazione WHO; msDBP ≥110 mmHg e/o msSBP ≥ 180 mmHg). Storia di angioedema, correlato o meno a farmaco. Anamnesi o evidenza di una forma secondaria di ipertensione, compresi, a titolo esemplificativo, uno qualsiasi dei seguenti: ipertensione parenchimale renale, ipertensione renovascolare (stenosi unilaterale o bilaterale dell’arteria renale), coartazione dell’aorta, iperaldosteronismo primario, malattia di Cushing, feocromocitoma, malattia renale policistica e ipertensione farmaco indotta. Attacco ischemico cerebrale transitorio (Transient Ischemic Attack -TIA) nei 12 mesi precedenti la Visita 1 o pregresso ictus in anamnesi. Anamnesi di infarto miocardico, chirurgia per bypass coronarico o qualsiasi intervento percutaneo coronarico (Percutaneous Coronary Intervention - PCI) nei 12 mesi precedenti la Visita 1. Anamnesi di fibrillazione atriale o di flutter atriale nei 3 mesi precedenti la Visita 1, o fibrillazione atriale o flutter atriale attivi all’ECG alla Visita 101. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint for this phase 2 study is change from baseline in central aortic systolic pressure (CASP) after 12 weeks of treatment with LCZ696 (4 weeks of 200 mg with an additional 8 weeks of 400 mg) or olmesartan (4 weeks of 20 mg with an additional 8 weeks of 40 mg). |
| L'end point primario é il cambiamento rispetto al basale della pressione sistolica dell'aorta (CASP) dopo 12 settimane con LCZ696 (4 settimane da 200 mg con addizionali 8 settimane da 400 mg) o olmesartan (4 settimane da 20 mg con addizionali 8 settimane da 40 mg). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| primary endpoint at Week 12 |
| 12 settimane |
|
| E.5.2 | Secondary end point(s) |
| 1. Change from baseline in mean central pulse pressure 2. Change from baseline in mean aortic pulse wave velocity 3. Change from baseline in mean central aortic systolic blood pressure at 52 weeks 4. Change from baseline in mean sitting systolic blood pressure 5. Change from baseline in mean sitting diastolic blood pressure 6. Change from baseline in mean sitting pulse pressure 7. Change from baseline in mean arterial pressure 8. Change from baseline in mean 24-hour systolic blood pressure 9. Change from baseline in mean 24-hour diastolic blood pressure 10. Change from baseline in mean 24-hour ambulatory pulse pressure |
| Pressioni aortiche centrali. Pressione differenziale centrale. Velocità dell’onda sfigmica aortica. Pressione arteriosa misurata in ospedale. Misurazione ambulatoria della pressione arteriosa nelle 24 ore. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| baseline, 12 weeks, and 52 weeks (1, 2, 4, 5, 6, 7, 8, 9, 10) baseline, 52 weeks (3) |
| basale, 12 settimane, e 52 settimane |
|
| 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 | 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 | 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 | No |
| E.8.2.3 | Other | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| 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 |
| Japan |
| Korea, Republic of |
| Taiwan |
| United States |
|
| 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
|
| LVLS 19/NOV/2014 |
| LVLS 19/11/2014 |
|
| 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 | 20 |
| 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 | 23 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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