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 |
High blood pressure where the cause of the high blood pressure is unknown. |
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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 assess the therapeutic equivalence of eprosartan (a new formulation containing only the active moiety eprosartan) with eprosartan mesylate (currently marketed formulation) on sitting diastolic blood pressure (DBP) in ambulatory subjects with mild to moderate essential hypertension after 8 weeks of treatment (monotherapy). |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of eprosartan with eprosartan mesylate on sitting systolic blood pressure (SBP), responder rate, and normalization rate after 8 weeks (monotherapy) and 12 weeks (add-on therapy) of treatment, and on sitting trough blood pressure at 12 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged ≥ 18 years
2. Subjects with history of mild to moderate essential hypertension for at least 2 months and with mean sitting SBP ≥ 140 mmHg and ≤ 179 mmHg; and mean sitting DBP ≥ 90 mmHg and ≤ 109 mmHg at screening (V1) and at baseline (V2)
3. Written informed consent to participate in the study before starting any study-specific procedures at V1 (screening)
4. Compliance with the study medication > 80% and < 120% during the 3-week placebo washout period.
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E.4 | Principal exclusion criteria |
1. Women of childbearing potential without hormonal, barrier or intrauterine contraception methods
2. Inability to discontinue all prior antihypertensive medications safely for the duration of the washout period, subjects on triple combination of antihypertensive drugs at V1 or subjects on dual combination with moderate hypertension (SBP≥160-179 mmHg and/or DBP ≥100-109 mmHg) at V1
3. Pregnant or breast-feeding female subject
4. Any secondary form of hypertension
5. Severe (Grade 3) hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg)
6. Presence of the differences greater than 20mmHg for SBP and 10mmHg for DPB on 3 consecutive readings at V1 or V2
7. Angina pectoris that is currently being treated with long acting nitrates, beta-blockers, or calcium channel blockers unless kept on stable doses for the duration of the study
8. Severe diabetes mellitus (HbA1c greater 8.5%) with metabolic complications (diabetic ketoacidosis, hyperosmolar hyperglycemia associated with dehydration)
9. Nonresponders to ACE inhibitors or angiotensin receptor blockers (ARBs), however, subjects known to be intolerant to ACE inhibitors are allowed except for a low-dose aspirin (75-325mg
per day)
10. Concomitant administration of lithium and NSAIDs except for a low-dose aspirin (75-325mg per day)
11. New York Heart Association (NYHA) Class IV congestive heart failure
12. Myocardial infarction or unstable angina within the preceding 90 days
13. Aortic and mitral valve stenosis, hypertrophic cardiomyopathy
14. Known or suspected hemo-dynamically significant bilateral renal artery stenosis or severe stenosis of a solitary functioning kidney
15. Severe renal impairment (creatinine clearance < 30 mL/min)
16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal and/or total bilirubin > 3 mg/dL
17. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
18. Active alcohol or drug abuse
19. Known hypersensitivity to the active substances of eprosartan or to any of its excipients, or to sulfonamide derived substances (such as HCTZ)
20. Administration of an investigational drug or device, or participation in an investigational trial within 30 days
21. Clinically significant laboratory abnormalities or medical conditions which, in the opinion of the Investigator, make them unsuitable for evaluation
22. Subjects withdrawn from the study cannot re-enter this trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in trough sitting DBP from baseline to end of Week 8. |
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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) |
1. Change in trough sitting SBP from baseline (V2) to end of Week 8 (V4).
2. Change in trough sitting DBP and trough sitting SBP from baseline (V2) to end of Week 12 (V5).
3. Responder rate at Week 8 (V4) and at Week 12 (V5) on monotherapy.
4. Normalization rate at Week 8 (V4) and Week 12 (V5) on monotherapy.
5. Responder rate at Week 12 (V5) in subjects with add-on HCTZ.
6. Normalization rate at Week 12 (V5) in subjects with add-on HCTZ. |
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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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Germany |
Hungary |
Poland |
Russian Federation |
United Kingdom |
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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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Last visit of the last subject |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 |