E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Arterial hypertension and glaucoma |
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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 |
To assess the influence of Nebivolol as compared to Bisoprolol on the peak systolic and end-diastolic blood flow velocity in the short and the long posterior ciliary artery. It is assumed that Nebivolol may influence the ocular perfusion positively by peripheral vasodilatation induced by the stimulation of the NO-system.
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E.2.2 | Secondary objectives of the trial |
To assess the influence of Nebivolol as compared to Bisoprolol - on the peak systolic and end-diastolic blood flow velocity in the central retinal artery - on the peak systolic and end-diastolic blood flow velocity in the ophthalmic artery - on the resistive index (RI) in the: a.short posterior ciliary artery b.long posterior ciliary artery c.central retinal artery d.ophthalmic artery - on the pulsatility index (PI) in the a.short posterior ciliary artery b.long posterior ciliary artery c.central retinal artery d.ophthalmic artery - on capillary blood flow in the retina - on the diameter of retinal vessels - on the Time average maximum velocity (TAMx) - on the Time average minimum velocity (TAMm) - on the blood pressure |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years or older 2. Stable glaucoma associated with a pathological excavation of the optical nerve head and visual field defects 3. No other previous eye surgery than cataract surgery and/or cyclophotocoagulation, deep sclerectomy, trabeculectomy or related surgical procedures which were performed > 4 weeks before study entry 4. Refractive error between – 6 and + 6 dpt 5. Arterial hypertension adequately and stable (≥ 3 months) treated in combination- or mono therapy with a beta-blocker except for current treatment with Nebivolol, Bisoprolol or Carvidilol (blood pressure prior to switch of the antihypertensive medication to the trial medication: < 140 mmHg SBP and < 90 mmHg DBP)
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E.4 | Principal exclusion criteria |
1. Secondary hypertension 2. Untreated heart failure or uncompensated heart failure 3. Sick-sinus-syndrome including heart blocks (SA node) and/or AV block 2nd and 3rd degree and/or significant arrhythmia and/or bradycardia < 50 bpm (in resting condition prior to treatment) 4. Cardiogenic Shock 5. Bradycardia (< 50 bpm prior to treatment) 6. Hypotension with systolic blood pressure < 90 mmHg 7. Known hypersensitivity to Nebivolol or Bisoprolol or any of the ingredients of the trial medication or any known hypersensitivity to ß-blockers 8. Bronchial hyperreactivity, bronchial asthma, or history of bronchial spasm 9. Patients with known SGPT (ALAT) and SGOT (ASAT) levels exceeding three times the upper limit of the investigator's normal range, known serum bilirubin > 1.75 mg/dl (> 30 µ mol/l) or clinical evidence of severe hepatic disease or hepatic failure 10. Untreated pheochromocytoma 11. Metabolic acidosis 12. Peripheral arterial occlusive disease > IIa (PAOD) or Raynaud’s syndrome 13. History of myocardial infarction within the last 3 months prior to study inclusion 14. Unstable angina pectoris 15. Prior or active malignancy in the previous 5 years except adequately treated basal cell/ squamous cell carcinoma of the skin or carcinoma in situ of the cervix 16. Previous treatment within 30 days prior to the beginning of the study or concomitant treatment with substances which may decrease the efficacy of the test substance(s) or may lead to drug interactions, for example: MAO inhibitors, systemic sympathomi- metics, intravenous application of calcium-antagonists of verapamil- or diltiazem-type or other antiarrhythmic agents except for intensive care, aldosterone analogues 17. Anticipated dose change of statins if patient is treated with statins already or anticipated need for statins if patient is currently not treated with statins 18. Previous topical and/or systemic glaucoma medication not stable for > 14 days prior to visit 2 19. Anticipated dose change of topical glaucoma medication (including dorzolamide) or anticipated dose change of magnesium-containing preparations 20. Patients with psychiatric diseases 21. Patients with a history of alcohol and/or drug abuse 22. Patients who are currently participating in another clinical study or who have received an investigational drug within 30 days prior to entering the study 23. Patients who are unwilling or unable to provide informed consent or to participate satisfactorily for the entire trial period 24. Women of childbearing potential without adequate contraception; medically acceptable methods are contraceptive implant (contraceptive injection, intrauterine device (IUD), or oral contraceptives taken for at least 3 months, which the patient agrees to continue using during the study. 25. Patients who are pregnant or lactate (Pregnancy should be ruled out by serum pregnancy test) 26. Intake of coffee and/or smoking < 2 hours before Laser Doppler Flowmetry |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variable: - Peak systolic blood flow velocity (PSV) in the short posterior ciliary artery - PSV in the long posterior ciliary artery - End diastolic blood flow velocity (EDV) in the short posterior ciliary artery - EDV in the long posterior ciliary artery
Secondary efficacy variable(s): - Changes of the peak systolic and end systolic blood flow velocity in the central retinal artery after 6 weeks of treatment - Changes of the peak systolic and end systolic blood flow velocity in the ophthalmic artery after 6 weeks of treatment - Changes of the resistive index (RI) after 6 weeks of treatment in - short posterior ciliary artery - long posterior ciliary artery - central retinal artery - ophthalmic artery - Changes of the pulsatility index (PI) after 6 weeks of treatment in - short posterior ciliary artery - long posterior ciliary artery - central retinal artery - ophthalmic artery - Time average maximum velocity (TAMx) - Time average minimum velocity (TAMm) - Retinal capillary blood flow, velocity and volume in the para-papillary region and the fovea - Vessel diameter of the retinal arteries - Changes of Blood pressure after 6 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 | Yes |
E.6.4 | Safety | No |
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 | Information not present in EudraCT |
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 | 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.8.3 |
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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 5 |