| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| Demonstrate the efficacy of the combination therapy of aliskiren 300 mg and HCTZ (12.5 mg and 25 mg) in hypertensive patients who do not show sufficient blood pressure response to a 4-week treatment of aliskiren 300 mg by testing the hypothesis of superior reduction in mean sitting diastolic blood pressure (msDBP) from baseline to end of study when compared to aliskiren 300 mg monotherapy. |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate the efficacy of the combination therapy of aliskiren 300 mg and HCTZ
(12.5 mg and 25 mg) in hypertensive patients who do not show sufficient blood
pressure response to a 4-week treatment of aliskiren 300 mg by testing the
hypothesis of superior reduction in mean sitting systolic blood pressure (msSBP)
from baseline to end of study when compared to aliskiren 300 mg monotherapy.
- Evaluate the safety and tolerability of the combination of aliskiren 300 mg and
HCTZ (12.5 mg and 25 mg) compared with aliskiren 300 mg monotherapy in
hypertensive patients who do not show sufficient blood pressure response to a 4-
week treatment of aliskiren 300 mg.
- Evaluate the proportion of patients achieving a blood pressure control target of <
140 / 90 mmHg at the end of study for all treatment arms |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
(For Full list, see protocol)
- Outpatients 18 years of age and older.
- Male or female patients are eligible.
- Patients with a diagnosis of hypertension:
- Newly diagnosed patients or patients who have not been treated for
hypertension within the 4 weeks prior to Visit 1 must have a msDBP ≥ 95 mmHg
and < 110 mmHg at Visit 1.
- All patients who have been treated for hypertension within the 4 weeks prior to
Visit 1 must have a msDBP > 85 mmHg and < 110 mmHg at Visit 2.
- All patients must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 4.
- Patients who are eligible and able to participate in the study, and who consent to
do so after the purpose and nature of the investigation has been clearly explained
to them (written informed consent) |
|
| E.4 | Principal exclusion criteria |
(For Full list, see protocol)
- Pregnant or nursing (lactating) women
- Women of child-bearing potential (WOCBP)
- Severe hypertension (msDBP ≥ 110 mmHg and/or msSBP ≥ 180 mmHg).
- History or evidence of a secondary form of hypertension.
- Known Keith-Wagener grade III or IV hypertensive retinopathy.
- Previous or current diagnosis of heart failure.
- History of hypertensive encephalopathy or cerebrovascular accident, transient
ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or
any percutaneous coronary intervention (PCI).
- Serum potassium < 3.5 mEq/L (mmol/L) or ≥ 5.3 mEq/L (mmol/L), serum sodium
less than the lower limit of normal or dehydration.
- Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based
on the investigator’s clinical judgment. Patients with diabetes mellitus enrolled in
this study should be well controlled. It is recommended that patients currently
being treated for diabetes mellitus be on a stable dose of oral antidiabetic
medication for at least 4 weeks prior to Visit 1.
- Current angina pectoris requiring pharmacological therapy.
- Second or third degree heart block without a pacemaker.
- Atrial fibrillation or atrial flutter at Visit 1, or potentially life threatening or any
symptomatic arrhythmia during the 12 months prior to Visit 1.
- Clinically significant valvular heart disease.
- Any medication, surgical or medical condition, which might significantly alter the
absorption, distribution, metabolism, or excretion of medications including, but not
limited to, any of the following:
- History of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection.
- History of active inflammatory bowel disease during the 12 months prior to
Visit 1.
- Currently active gastritis, duodenal or gastric ulcers, or history of
gastrointestinal bleeding during the 3 months prior to Visit 1.
- Evidence of hepatic disease as determined by any one of the following: ALT or
AST values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a
history of esophageal varices, or a history of portocaval shunt.
- Evidence of renal impairment as determined by any one of the following: serum
creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic
syndrome.
- Current treatment with cholestyramine or colestipol resins.
- History of hypersensitivity to any of the medications or to drugs belonging to the
similar therapeutic class (ARB’s, ACE-I’s, thiazide diuretics, or other sulfonamide
derived drugs) as the medications.
- History of angioedema due to usage of an ACE-I or ARB.
- 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.
- History of gouty arthritis.
- History or evidence of drug or alcohol abuse within the last 12 months.
- Any surgical or medical condition, which in the opinion of the investigator, may
place the patient at higher risk from his/her participation in the study, or is likely to
prevent the patient from complying with the requirements of the study or
completing the study.
- Patients who previously participated in a clinical trial that contained the treatment
combination of aliskiren/HCTZ and qualified to be randomized or enrolled in the
active drug treatment period.
- Use of other investigational drugs at the time of enrollment, or within 30 days or 5
half-lives of enrollment, whichever is longer.
- History of noncompliance to medical regimens or unwillingness to comply with the
study protocol.
- Any condition that in the opinion of the investigator or the Novartis Medical Monitor
would confound the evaluation and interpretation of efficacy and/or safety data.
- Persons directly involved in the execution of this protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is change from baseline (visit 5) in mean sitting diastolic blood pressure. For each patient, the last post-baseline measurement during the double-blind period will be carried forward to Week 8 as the endpoint measurement for the variable to be analyzed. The primary analysis timepoint will be the endpoint. |
|
| 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 | 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 | Yes |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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