E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Seasonal allergic rhinitis |
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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 examine the change in expression of key allergy targets in the nose following exposure to allergen. •To evaluate the effect of intranasal corticosteroids treatment on the change in target expression following allergen challenge. •Identify biomarkers associated with clinical response to allergen and corticosteroids.
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E.2.2 | Secondary objectives of the trial |
•Examine the relationship between changes in target expression and clinical measures of allergen response. •Identify nasal and systemic biomarkers associated with changes in target expression and with the clinical response to allergen and corticosteroids. •Evaluate nasal pathology following allergen challenge and corticosteroid treatment
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
•Males or females aged between 18 and 65 years inclusive •Female subjects of childbearing potential must be using effective forms of contraception (i.e. abstinence, oral contraceptives, Norplant*, documented placement of intrauterine device (IUD) with failure rate of less than 1%, a diaphragm with spermicide, a condom and diaphragm with spermicide or Depo-Provera*) for at least one month prior to screening and throughout the study period. •Subjects with a known history of SAR with a clinically significant positive skin prick test/RAST to any of 6 common allergens •No signs or symptoms of rhinitis outside of the relevant airborne allergen season(s) |
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E.4 | Principal exclusion criteria |
•As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study •Subject is female who is pregnant or lactating •History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessments •History of abnormal bruising or bleeding •Symptoms of rhinitis at inclusion indicated by total VAS score of >40 for the combined symptoms scores for blockage, rhinorrhoea, sneezing, itching) or a single symptom with a VAS score >20 •Subjects not showing a nasal response to allergen concentration =< 10,000 BU/ml •Subjects with positive skin prick test for Dust House Mite •Subjects showing demonstrating hypersensitivity to the vehicle challenge at screening •Concurrent purulent nasal infection •Requirement for > 250µg inhaled FP > 500µg inhaled budesonide propionate (BDP; or equivalent) per day as treatment for asthma •Inability to abstain from all intranasal or oral medication to treat nasal allergy from study visit 1 to the completion of the study including: sodium cromoglycate, anti-histamines, alpha-adrenergic agonists and corticosteroids •Use of any medications that significantly inhibit the Cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole •Current smokers or anyone that has regularly smoked over the last 6 months •Female subjects who are unwilling or unable to use an appropriate method of contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
Target Expression: •Assessment of protein expression by western blotting and/or immunohistochemistry in nasal biopsy tissue •Assessment of protein expression in nasal lavage fluid by ELISA and/or chemiluminescent assay. • Assessment of mRNA expression by Taqman RT-PCR and/or LCMD in nasal biopsy tissue
Clinical Measures: •Symptom scores (total nasal symptom score and components) •Measures of nasal resistance: acoustic rhinomanometry, nasal peak inspiratory flow (PnIF) •Nasal nitric oxide •Clinical events
Biomarkers: •Inflammatory cell counts in nasal lavage fluid •Inflammatory mediator (e.g. histamine, prostaglandin-D2, IL-5) expression assessed by western blotting and/or immunohistochemistry in nasal biopsy tissue •Inflammatory mediator expression in nasal lavage fluid assessed by ELISA and/or chemiluminescent assay •Differential cell counts in whole blood •Inflammatory mediator expression in plasma or in frozen white blood cells assessed by ELISA and/or chemiluminescent assay •Genotyping: where appropriate changes in target/biomarker expression will also be related to polymorphic variation within their corresponding genes |
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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 | Yes |
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) | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |