E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male subjects with seasonal allergic rhinitis to grass but otherwise healthy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039776 |
E.1.2 | Term | Seasonal allergic rhinitis |
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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 explore the activity of UR-63325 in a model of allergic rhinitis induced by nasal allergen challenge to known allergic rhinitis patients otherwise healthy, through clinical and physiological measures including sneezing, TNSS (total nasal symptom score) and nasal peak inspiratory flow. |
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E.2.2 | Secondary objectives of the trial |
- To explore the pharmacokinetics of UR-63325 and metabolites in plasma after administration of repeated oral doses for 7 days. - To explore the biological effects of UR-63325 in known allergic rhinitis patients otherwise healthy through effect on several markers of inflammation and allergic reactions, including cytokines in nasal exudates, and overall leukocyte and differential leukocyte density in nasal lavage. - To describe the profile of adverse effects of UR-63325 in known allergic rhinitis patients otherwise healthy after 7 days of administration. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Caucasian males between the ages of 18 and 55 2. No clinically relevant abnormal physical findings at the screening examination 3. No clinically relevant abnormal ECG at the screening examination 4. No clinically relevant abnormal resting blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and resting heart rate (50-100 bpm) 5. Body Mass Index of 19.0-29.9 (kg/m2) 6. Ability to communicate well with the investigator and to comply with the requirements of the entire study. 7. Availability for daily telephonic follow-up and willingness to provide contact details to be located at any time during the treatment days. 8. Provision of written informed consent to participate (prior to any study-related procedures being performed) as shown by a signature on the volunteer consent form and to be able to adhere to the study restrictions and examination schedule 9. Subjects with history of seasonal allergic rhinitis to grass within the previous two years 10. Positive skin prick test to timothy grass pollen (wheal difference with negative control ≥ 3 mm) at screening 11. Subjects with positive response to screening nasal challenge with increasing doses of timothy grass pollen (symptoms worsening (TNSS≥4-6) within one hour after last nasal allergen challenge) 12. Baseline FEV1 80% predicted and baseline FEV1/FVC 70% predicted 13. In case of sexually active men who have not been sterilized surgically, use of a double contraception method during intercourse to prevent a pregnancy from possibly damaged sperm: -intrauterine device (IUD) or hormonal contraception plus condom or diaphragm or spermicide, or -condom plus diaphragm, or -abstinence during the clinical study until the Follow-up visit
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E.4 | Principal exclusion criteria |
1. Symptoms of allergic rhinitis within 2 weeks prior to screening 2. Upper respiratory infection or sinusitis within 14 days of screening and also within 14 days of study start in each of the two periods 3. Structural nasal abnormalities or nasal polyps on examination, a history of nose bleeding or recent nasal surgery 4. History of asthma or asthmatic symptoms or other respiratory disease other than rhinitis within the last 2 years or FEV1<80% of predicted at screening or baseline 5. Contraindication to nasal corticosteroids 6. Administration of any investigational drug in the period of 3 months before first entry to the study. Participation in any other investigational study 7. Subjects who have taken any prescribed or over the counter drug (including antacid drugs and herbals), with the exception of paracetamol (up to 3 g per day) within 4 weeks prior to the screening or at least 10 half lives of the administered drug 8. History of immunotherapy in the past 3 years or currently on an immunotherapy treatment course 9. Subjects who have taken inhaled or local (nasal or inhaled) corticosteroids within 4 weeks prior to the screening 10.Subjects who have undergone major surgery or have donated or lost more than 500 mL of blood within 8 weeks before entry to the study 11.History of serious adverse reaction or hypersensitivity to any drug 12.Subjects who have previous history of neurological disease, including previous epilepsy or neuromuscular diseases, or who have had previous clinically significant psychiatric disease, including depression, schizophrenia or anxiety disorders 13.Inability to communicate or co-operate with the investigator because of a language problem, poor mental development or impaired cerebral function 14.Unwillingness to be easily located at any time during the 7 days of treatment and in general during the study. 15.Smoker of > 5 cigarettes per day or unwilling to stop smoking for the duration of study (screening to end of follow-up) 16.Drinker of more than 5 cups daily of beverage containing caffeine 17.Daily alcohol intake bigger than 3 units per day (one unit=8 g or about 10 mL of pure alcohol) or unwilling to stop alcohol intake for the duration of the study (screening to end of follow-up) 18.History of drug dependence other than tobacco within the past 2 years 19.Positive urine drug screen for drugs 20.Subjects with any clinically significant abnormality following review of pre-study laboratory tests or on direct questioning and physical examination, including known or suspected HIV, HBV and HCV infection 21.Subjects with sucrose intolerance 22.Subjects who forfeit their freedom by administrative or legal award or who are under guardianship 23.Subjects who are unwilling to give their informed consent 24.Any other condition which, in the opinion of the investigators, is likely to interfere with the successful collection of the measures required for the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The primary endpoint will be the change from screening in the nasal and ocular scores at each time point after nasal allergen challenge. - The maximum score and the time course and AUC of symptoms will be compared for each of the treatment groups. Individual clinical symptoms and number of sneezes will be also compared. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Incomplete 2 ways crossover where each volunteer receives 2 of the 3 possible treatments |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |