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 | 14.0 |
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 assess the effect of single (150 mg) and multiple (150 mg and 300 mg) doses of aliskiren on the diuretic efficacy (efficacy index) of 60 mg furosemide at steady state. |
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E.2.2 | Secondary objectives of the trial |
•To assess the effect of multiple doses of aliskiren (150 mg and 300 mg) on the pharmacokinetics of 60 mg furosemide.
•To assess the effect of multiple doses of aliskiren (150 mg and 300 mg) on blood pressure when co administered with 60 mg furosemide at steady state.
•To assess the effect of single and multiple doses of aliskiren (150 mg) on urinary sodium, urinary potassium, and creatinine clearance when co administered with 60 mg furosemide at steady state.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females, aged between 18 and 75 years (inclusive) at screening.
2. Female patients of childbearing potential must be using an acceptable form of contraception, Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to screening.
Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to screening.
3. All patients must be diagnosed at least 3 months prior to screening with either systolic or diastolic heart failure with signs and symptoms of congestive heart failure and NYHA functional class II to III symptoms AND be on stable medication for at least 12 weeks (furosemide only stable for 3 weeks).
4. A patient has to fulfill either a), or b) to qualify for participation.
(a) Patients with a documented left ventricular ejection fraction (LVEF) greater than 20% but lower than 40%.
(b) Patients with a documented left ventricular ejection fraction (LVEF) greater than 40% AND with a history of NT-pro-BNP > 400 pg/mL (or BNP > 100 pg/mL) within 12 months of screening.
5. Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) of maximum 40 kg/m2.
6. Patients must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and to understand and sign the written informed consent.
For a detailed list of inclusion criteria, please refer to the full protocol.
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E.4 | Principal exclusion criteria |
1. Treatment with Angiotensin Receptor Blockers (ARBs), aldosterone receptor antagonists and diuretics (other than furosemide) within 3 weeks of first dose and during the study. Beta blockers are permitted providing the dose has been stable for at least 3 weeks before the first dose and remains so throughout the study.
2. Hypertrophic cardiomyopathy (HCMP).
3. If a subject is currently treated with furosemide, the dose must be stable for at least 3 weeks before the first dose and the dose must not exceed 60 mg daily. If a subject is not pre-treated with furosemide, this does not apply.
4. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors within 72 hours prior to first dose or during the 24 hour in-clinic study periods.
5. Treatment with sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) within 72 hours prior to first dose or during the 24 hour in-clinic study periods.
6. Commencing any new medication during the conduct of the study that could affect renal function or serum creatinine.
7. Stable heart failure requiring treatment with both an ACE inhibitor and an ARB.
8. msSBP ≥160 mmHg and/or msDBP ≥ 100mmHg and/or secondary forms of hypertension.
9. Persistent sitting systolic blood pressure <90 mmHg.
10. Signs or symptoms of dehydration (BUN/sCr ratio; orthostatic hypotension) as judged to be clinically significant by the investigator.
11. Uncontrolled diabetes based on the investigator’s clinical judgement, and glucose/HbA1c measurements.
12. History of angioedema.
For a full list of exclusion criteria, please refer to the full protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- urinary sodium concentration in 0-4h and 0-24h urine collection fractions
- urine volume in 0-4h and 0-24h urine collection fractions
- urinary furosemide concentration in 0-4h and 0-24h urine collection fractions |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points not applicable according to the protocol design. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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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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Provided in the protocol. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |