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 |
Rapid (unknown cause) swelling (edema) of the dermis (layer of skin between the epidermis and subcutaneous tissues). |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 efficacy of the bradykinin (BK) B2 antagonist, Icatibant, in the relief of symptoms resulting from moderate to severe angioedema of the face, neck, arms, genitals, tongue, pharynx and larynx, where the diagnosis is of Idiopathic Angioedema - unresponsive to antihistamines. |
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E.2.2 | Secondary objectives of the trial |
These will be: Time to first onset of relief; Response rate at 4 hours after start of treatment; Visual Analogue Scale (VAS) at 2, 4, 6, 8, 10, 12, 14, 18, 24, 36 and 48 hours post attack Time to almost complete symptom relief; Need for rescue therapy within 24 hours; Adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female; • Age ≥ than 18 years; • C1-inhibitor functional levels ≥ 50% of normal values • Current oedema attack must be in the cutaneous or mucosal areas; • Current oedema attack must be moderate to severe; • Women of childbearing potential must have a negative urine pregnancy test; • Signed written Informed Consent given |
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E.4 | Principal exclusion criteria |
• Diagnosis of angioedema of any defined cause, for example, allergic, hereditary/acquired C1-Inhibitor deficiency, ACE inhibitor induced angioedema, drug and/or food induced angioedema; • Urticaria-associated angioedema • Participation in a clinical trial of another Investigational Product (IP) within the past month; • Treatment with any other medication likely to influence the outcome since onset of the current oedema attack; • On treatment with ACE inhibitors; • Evidence of severe coronary artery disease based on medical history or screening examination; • Pregnancy and/or breast-feeding; • Mental or physical condition rendering the subject, in the opinion of the investigator, unable to understand the nature, scope and possible consequences of the study; • Unlikely to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the time to onset of symptom relief. The severity of the symptoms will be measured using a Visual Analogue Scale (VAS) of 100 mm length. The first absolute reduction by 20% of pre-treatment value, confirmed at three consecutive measurements after treatment, is defined as the onset of symptom relief. The difference in time to onset of symptom relief is tested using the VAS with highest score at baseline, if baseline values are identical hierarchical value will be as follow: dyspnea>dysphagia>swelling |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint is the time to onset of symptom relief. |
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E.5.2 | Secondary end point(s) |
Time to first onset of relief; Response rate at 4 hours after start of treatment; VAS at 4 hours; Time to almost complete symptom relief; Need for rescue therapy within 24 hours; Adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint is the time to onset of symptom relief. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 29 |