E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
Chronische Spontane Urtikaria |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Spontaneous Urticaria |
Chronische spontane Nesselsucht |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072757 |
E.1.2 | Term | Chronic spontaneous urticaria |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue 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 effects of standard dose (20 mg) and higher than standard dose of bilastine (40 mg and 80 mg) on disease activity in patients with chronic spontaneous urticaria. |
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E.2.2 | Secondary objectives of the trial |
- To assess the effects of standard dose (20 mg) and higher than standard dose of bilastine (40 mg and 80 mg) on quality of life impairment in patients with chronic spontaneous urticaria.
- To assess the safety of bilastine in doses of 20 mg, 40 mg and 80 mg in chronic spontaneous urticaria patients by documentation of adverse events.
- To assess the effects of standard dose (20 mg) and higher than standard dose of bilastine (40 mg and 80 mg) on biomarkers of chronic spontaneous urticaria, such as substance P and D-Dimers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female aged 18 years and older
- History of active csU (urticaria wheals) with or without associated angioedema for at least three days per week over the last 6 weeks prior to visit 1. Urticaria symptoms must comprise wheals and itch
- History of failed treatment with an antihistamine other than bilastine in standard (licensed) dose.
- UAS7 of ≥14 during baseline
- Informed consent signed and dated
- Able to read, understand and willing to sign the informed consent form and abide with study procedures
- Willing, committed and able to return for all clinic visits and complete all study-related procedures
- In females of childbearing potential: negative pregnancy test; females willing to use highly effective contraception (Pearl-Index < 1) --> a woman will be considered not of childbearing potential if she is post-menopausal for > 2 years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
- No participation in other clinical trials 4 weeks before and after participation in this study
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E.4 | Principal exclusion criteria |
- Chronic spontaneous urticaria patients with a known resistance to bilastine in standard (licensed) dose
- Isolated presence or domination of inducible forms of urticaria or cholinergic urticaria (no chronic spontaneous urticaria)
- History of adverse reactions to bilastine or known hypersensitivity to bilastine or its ingredients
- Intake of oral corticosteroids or intravenously applied corticosteroids within 28 days prior to screening visit
- Use of depot corticosteroids within 3 months prior to screening visit (inhaled corticosteroids are allowed)
- Use of systemic immunosupressants/immunomodulators such as ciclosporin, dapsone, metotrexate, and comparable drugs within 28 days prior to screening visit.
- Use of UV-therapy within 28 days prior to visit 1
- Significant medical condition, in the opinion of the Investigator, rendering the patient immunocompromised or not suitable for a clinical trial
- Significant concomitant illness, in the opinion of the Investigator, that would adversely affect the subject’s participation or evaluation in this study
- Subjects for whom there is concern, in the opinion of the Investigator, about compliance with the protocol procedures
- The presence of a permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract)
- Presence of active cancer which requires chemotherapy or radiation therapy
- Presence of alcohol abuse or drug addiction
- Pregnancy or breast-feeding
- Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz)
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparison of the rate of complete responders (reduction of the UAS7 by at least 90% (as compared to baseline) or a UAS7 ≤ 3) between the second (20 mg bilastine), fourth (20 mg or 40 mg bilastine) and sixth week (20 mg, 40 mg or 80 mg bilastine) of the treatment phase. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
In the second, fourth and sixth week of the treatment phase. |
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E.5.2 | Secondary end point(s) |
- Comparison of additional responder rates between the second (20 mg bilastine), fourth (20 mg or 40 mg bilastine) and sixth week (20 mg, 40 mg or 80 mg bilastine) of the treatment phase.
- Comparison of the quality of life changes (based on the CU-Q2OL) between baseline, the first/second (20 mg bilastine), third/fourth (20 mg or 40 mg bilastine) and fifth/sixth week (20 mg, 40 mg or 80 mg bilastine) of the treatment phase.
- Description and comparison of the type and frequency of adverse events during treatment with bilastine 20 mg, 40 mg and 80 mg.
- Comparison of biomarker levels during no treatment and treatment with bilastine 20 mg, 40 mg and 80 mg.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Depends on the end point. See above. |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Disease activity controlled dose escalating study |
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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 | |
E.8.9.1 | In the Member State concerned days | |