E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Orthostatic intolerance means the defective adaptation of the cardiovascular system to the upright position. One of the major Form of this disorder, the postural orthostatic tachycardia syndrome (or POTS), is characterized by an intense increase of the heart rate at upright position without a drop in blood pressure. Patients complain of lightheadedness, fatigue or nausea at upright posture. |
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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 |
‚Orthostatic tolerance’ part: change in the heart rate at upright position after 20 min of passive orthostatism.
‚Sympathicus’ part: heart rate at given blood pressure (= standardised point on the parasympathetic baroreflex curve). The measurements are carried out in horizontal Position under rest. |
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E.2.2 | Secondary objectives of the trial |
‚Orthostatic tolerance' part: • duration of the passive orthostatic load until the appearance of a presyncope • minimum heart rate during a presyncope • minimum blood pressure during a presyncope • hemodynamics (stroke volume, cardiac output , peripheral resistance) on the tilting table.
‚Sympathicus’ part: • hemodynamics (stroke volume, cardiac output, peripheral resistance) and sympathetic activity at rest and their changes during cardiovascular tests • cardiac and sympathetic baroreflex sensitivity • sensitivity of the blood pressure to the vasoactive agents sodium nitroprusside and phenylephrine • concentration or activities of hormones regulating the cardiovascular system |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male subject aged 18-40 years • body mass index: 18-30 kg/m² • blood pressure <=160/100 mm Hg • state of health that allows participation in the clinical trial established by medical history, full physical examination and laboratory parameter • ability and willingness to cooperate • written informed consent
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E.4 | Principal exclusion criteria |
• any diseases or functional impairments which in the investigators opinion should exclude the patient from participating in the clinical trial, e .g. evidence that the study medication could be ineffetive or unsave • intake of non-authorized concomitant medication within 4 weeks prior to study entry • Participation in another clinical trial within the 4 weeks prior to study entry • legal incompetence or other circumstances which do not allow the subject to fully understand the character, relevance and importance of the clinical trial • history of alcohol or drug abuse, or both • known or assumed secundary hypertension, e. g. pheochromocytoma • medical history of known or current functional disorders of the kidney (serum creatinine > 130 µM or 1.47 mg/dl) or liver (GOT/GPT > 2 times the ULN, GGT > 3 times the ULN)
For the part ‚orthostatic tolerance’: o because of a restriciton on use for Reboxetin: hypertension, seizure disorder, urinary retention, glaucoma, attempted suicide, allergic diathesis; incompatibility against Reboxetin o because of a restriciton on use for Metoprolol: asthma bronchiale, psoriasis
• Diabetes mellitus (Diabetes mellitus as defined by the ADA/WHO/DDG: two fasting glucose measurements above 126 mg/dL (7.0 mmol/l) is considered diagnostic for diabetes mellitus. Fasting is defined as abstinence from food for at least 8 hours.) • heart insufficiency NYHA stage III and IV • coronary heart disease • peripheral arterial occlusive disease (PAOD) • known cerebrovascular diseases (transient ischemic attack , ischemic or hemorrhagic insult) • ventricular extrasystole (Lown III-V), absolute arrhythmia at atrial fibrillation or atrial flutter • resting heart rate <60/min (Contraindication for Ivabradin) • for orthostatic part: resting heart rate <55/min • contraindications against the study drugs • relevant neurological or psychiatric dieseases (bipolare disorders, depressions, schizophrenia, Gilles de la Tourette-Syndrom, psychosis) • anamnestic benign hyperplasia of the prostate with retention of urine • known primary or secondary pulmonary hypertension • Dysthyreosis, viz. hyper- or hypothyreosis (patients with stable intake of thyroid hormones for at least 6 month and an euthyroid metabolism can be included in the clinical trial • subjects for whom there is concern about compliance with the protocol procedures • persons who are detained officially or legally to an official institute (according to AMG § 40 (1) 4) |
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E.5 End points |
E.5.1 | Primary end point(s) |
‚Orthostatic tolerance’ part: change in the heart rate at upright position after 20 min of passive orthostatism.
‚Sympathetic’ part: heart rate at given blood pressure (= standardised point on the parasympathetic baroreflex curves). The measurements are carried out in horizontal Position under rest. |
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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 | 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) | 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 | 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
| 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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | 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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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 | |
E.8.9.1 | In the Member State concerned days | |