E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 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 |
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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 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. |
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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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following 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
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E.4 | Principal exclusion criteria |
Patients with any of the following physiological states or concomitant medical conditions at Visit 1, Visit 2, Optional Visit 201 or Visit 3 will be excluded from participation in the study.
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, drug-induced 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
14. Patients unwilling or unable to discontinue safely the use of current antihypertensive medications for a period up to 12 weeks, as required by the protocol. Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those anti-hypertensive medications requiring tapering down commencing at Visit 1 and completing by Visit 2
15. History of drug or alcohol abuse within the last 1 year
16. History of angioedema, drug-related or otherwise
17. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
18. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
19. Any surgical or medical condition which, at the discretion of the investigator, places 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 the trial period
20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
21. Pregnant or nursing (lactating) women, where pregnancy is 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)
22. Persons directly involved in the execution of this protocol
23. Third shift or night workers or upper arm circumference of > 42 cm.
24. Any condition – not identified in the protocol – that in the opinion of the investigator or the sponsor Medical Monitor would confound the evaluation and interpretation of the efficacy and/or safety data
For a complete list of exclusion criteria please refer to the study protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
24 hours mean systolic ambulatory blood pressure |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 8 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint: 24 hours mean diastolic ambulatory blood pressure |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 8 weeks of treatment |
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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 | 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.8.3 |
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 | 17 |
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 |
Belgium |
Canada |
Italy |
Slovakia |
Spain |
Taiwan |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 23 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 23 |