| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015488 |
| E.1.2 | Term | Essential hypertension |
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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 demonstrate that 4 weeks of treatment with SPC Aliskiren 300 mg / Amlodipine 10 mg at Visit 6 provide additional mean sitting diastolic blood pressure reduction in hypertensive patients not adequately responding (i.e., msDBP ≥ 90 mmHg) to 4 weeks of treatment with an Angiotensin-receptor blocker plus Amlodipine 10 mg in SPC (Olmesartan 40 mg / Amlodipine 10 mg) at Visit 5. |
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| E.2.2 | Secondary objectives of the trial |
To evaluate the effects of 4 weeks of treatment with SPC Aliskiren 300 mg / Amlodipine 10 mg at Visit 6 in patients not adequately responding (i.e., msDBP ≥ 90 mmHg) to 4 weeks of treatment with an Angiotensin-receptor blocker plus Amlodipine 10 mg in SPC (Olmesartan 40 mg / Amlodipine 10 mg) on the difference in mean sitting systolic blood pressure, pulse pressure, heart rate, normalization, control and responder rate at Visit 5 (s. Section 7.4).
To assess the safety and tolerability of Aliskiren 300 mg / Amlodipine 10 mg.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patients 18 years
2. Patients with essential hypertension:
- At Visit 1, untreated (never been treated with antihypertensives or in the last 4 weeks not been treated with antihypertensives) patients must have an msDBP 100 mmHg and < 110 mmHg and msSBP 160 and < 180 mmHg and treated patients need to have an msDBP < 110 mmHg and msSBP < 180 mmHg. Untreated patients can be included as soon as the safety laboratory parameters are available, but not at the day of Visit 1. This inclusion visit will be recorded as Visit 3 in the CRF.
- At Visit 2, patients previously treated for hypertension need to have an msDBP 100 mmHg and < 110 and msSBP 160 and < 180 mmHg for entry into the first treatment phase. Patients previously treated for hypertension who have an msDBP < 100 mmHg and/or msSBP < 160 mmHg at Visit 2 will continue the wash-out phase and will be again evaluated with regard to BP criteria at Visit 3. Untreated patients do not perform Visit 2.
- At Visit 3, which is not performed for patients who entered the first treatment phase already at Visit 2, patients need to have an msDBP 100 mmHg and < 110 mmHg and msSBP 160 and < 180 mmHg for entry into the first treatment phase.
- At Visit 5, all patients need to have an msDBP 90 mmHg for entry into the second treatment phase
3. Written informed consent to participate in the study prior to any study procedures
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| E.4 | Principal exclusion criteria |
1. Patients with controlled blood pressure levels (msSBP < 140 mmHg and msDBP < 90 mmHg) under current antihypertensive therapy at Visit 1.
2. msDBP 110 mmHg or msSBP 180 mmHg at any time between Visit 1 and baseline
3. Inability to completely discontinue all antihypertensive medications safely for a period of up to 2 weeks, as required by the protocol
4. Known Keith-Wagener grade III or IV hypertensive retinopathy
5. Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal artery stenosis or pheochromocytoma
6. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures, known or suspected contraindications to angiotensin II receptor blockers, direct renin inhibitors or to calcium channel blockers as described in the SmPC (particularly Olmesartan 10-40 mg, Amlodipine 5-10 mg, Aliskiren 300 mg)
7. Concurrent treatment with cyclosporine or quinidine or verapamile at Visit 1 or during the trial
8. History of angiooedema due to Aliskiren treatment.
9. Bilateral renal artery stenosis
10. Heart failure NYHA II-IV
11. Second or third degree heart block without pacemaker
12. Current angina pectoris requiring pharmacological therapy
13. Concomitant potentially life-threatening arrhythmia or symptomatic arrhythmia
14. Clinically significant valvular heart disease
15. Transient ischemic cerebral attack, stroke, hypertensive encephalopathy or myocardial infarction prior to Visit 1
16. Type 1 diabetes mellitus
17. Type 2 diabetes mellitus with poor glucose control as defined by persistent fasting blood glucose > 11 mmol/l or > 200 mg/dl at Visit 1.
18. Advanced aortic stenosis
19. Shock and cardiogenic shock
20. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following:
History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
Currently active inflammatory bowel syndrome within 12 months prior to Visit 1
Currently active gastritis, ulcers or gastrointestinal/ rectal bleeding (hemorrhoids not included)
Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/ injury
Evidence of hepatic disease or cholestasis as determined by any one of the following: ALT or AST values > 2 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt, obstruction of the biliary tract
Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 x ULN or active acute glomerulonephritis at Visit 1, a history of dialysis, or a history of nephrotic syndrome
Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator
21. Therapy resistant hypokalemia, hypercalcemia, symptomatic hyperuricemia or sodium depletion (< 134 mmol/l), patients with volume depletion.
22. History of any severe, life-threatening disease
23. History of drug or alcohol abuse within the last 2 years
24. History of non-compliance to medical regimens, or those patients unwilling to comply with the trial protocol.
25. Any condition, which in the judgment of the investigator or medical monitor, would jeopardize the evaluation of efficacy or safety
26. Any surgical or medical conditions which, at the discretion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing it
27. Unwillingness or inability to give informed consent
28. Study personnel or first degree relatives of investigator(s) must not be included in the study
29. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
30. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
31. Women
o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml))
o who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The aim of this multicenter open-label trial is to evaluate the reduction in trough msDBP by a 4-week treatment with the single pill combination of Aliskiren 300 mg / Amlodipine 10 mg SPC in hypertensive patients not adequately controlled by Olmesartan 40 mg in SPC combination with Amlodipine 10 mg. The main interest is the estimation and testing of the changes in BP between Visit 5 and Visit 6. |
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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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 40 |
| 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 | Information not present in EudraCT |
| 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 | 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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