E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate hypertension. |
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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 |
The primary objective of the study is to assess the efficacy of 2.5, 10, 35 and 50 mg AVE 7688 once daily on the change from baseline in trough seated diastolic blood pressure (SeDBP) , at the end of 12 weeks of treatment in patients with mild to moderate essential hypertension. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives, in order of importance, are: - To assess the efficacy of 2.5, 10, 35 and 50 mg AVE 7688 once daily on the change from baseline in trough seated systolic blood Pressure (SeSBP) at the end of 12 weeks of treatment. - To compare the percentages of responders after 12 weeks of treatment. - To evaluate the long-term safety and tolerability of AVE7688 at doses of 2.5, 10, 35 or 50 mg, with particular attention to angioedema.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients, 18 years of age or older, with mild-to-moderate, treated or untreated, essential hypertension, as defined by the JNC VII guidelines, who meet the following BP eligibility criteria: - At the first qualifying visit in the placebo lead-in phase (either visit P2 or P3), mean SeSBP ≥140 mm Hg and <180 mm Hg and mean SeDBP ≥90 mm Hg and <110 mm Hg (mean of at least 3 readings) - At the second qualifying visit in the placebo lead-in phase (either visit P3 or P4 separated from the first qualifying visit by at least 1 week), SeSBP ≥140 mm Hg and <180 mm Hg and mean SeDBP ≥90 mm Hg and <110 mm Hg (mean of at least 3 readings). If the patient does not meet the criteria at the second qualifying visit, he or she will be excluded from randomization. - The patient can be included in the study only when the variability between the mean BP measurements on the two consecutive qualifying visits (either P2 and P3 or P3 and P4 (if applicable)) is less or equal than 7 mm Hg for SeDBP.
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E.4 | Principal exclusion criteria |
Criteria related to study methodology: - Refusal or inability to give informed consent - Patients who have previously been treated with AVE7688 - Patients who cannot stop their anti-hypertensive treatment (e.g., ACE-I (angiotensin convertin enzyme inhibitor), ARB (angiotensin receptor blocker), CCB (calcium channel blocker), diuretics, AB (alpha blocker), BB (beta blocker), Hydralazine, Rauwolfia alkaloids - Known history of secondary hypertension, including patients with endocrine disorders such as pheochromocytoma, active hyperthyroidism, or untreated hypothyroidism - Severe hypertension, defined as SeSBP ≥180 mm Hg or SeDBP ≥110 mm Hg - Women of child bearing potential (i.e. female patients who are not postmenopausal or surgically sterile), who have a positive serum pregnancy test, or who do not agree to use an accepted method of contraception - Women who are breast feeding - Patients with non-cardiac progressive fatal disease - Patients with immunological or hematological disorders - Requirement for concomitant treatment that could bias the primary evaluation, e.g. long-term treatment with anti-psychotic compounds or long-term steroid use - Unstable insulin-dependent diabetes mellitus - History of stroke, intracranial hemorrhage or transitory ischemic attack within the previous year - Likelihood of poor compliance both with treatment and study design, including social and geographical reasons - Patient is the investigator, sub-investigator, research assistant, pharmacist, study coordinator, or other staff member or relative thereof directly involved in the conduct of the study - Administration of any investigational drug within the preceding 30 days. Investigational drug is defined as any agent (placebo or active drug) dispensed as part of a research study - Abuse of drugs or alcoholic beverages within 1 year prior to the start of the study - Patients taking herbal or dietary compounds that have the potential to influence blood pressure
Criteria related to ACE-inhibition - Contraindications to losartan-potassium as per local package insert - History of hypersensitivity or angioedema with ACE inhibitors or NEP inhibitors, patients with hereditary or idiopathic angioedema, patients with allergic reaction in which urticaria or angioedema was the manifestation - Impaired hepatic function (i.e., AST and/or ALT >1.5 x upper limit of normal range) - Known unilateral or bilateral renal artery stenosis - Serum potassium ≥ 5.5 mmol/L - Impaired renal function (i.e. calculated creatinine clearance < 50 ml/min)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change from baseline in trough SeDBP at week 12.
The secondary efficacy endpoints, in a hierarchical order, are: - The change from baseline in trough SeSBP at week 12 - The percentage of responders in each treatment group at week 12, where responders are defined as follows: . Patients with BP ≤140/90 mm Hg after 12 weeks, or . Patients with a reduction from baseline in SeDBP of ≥10 mm Hg or in SeSBP of ≥20 mm Hg
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
losartan potassium (as calibrator) |
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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.8.5 | The trial involves multiple Member States | Yes |
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 |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |