E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 evaluate the effect of treatment with repeat oral doses of GW274150 for 14 days on the late asthmatic response (LAR) to inhaled allergen in mild asthmatic subjects compared with placebo |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect on bronchial hyper-reactivity in response to methacholine challenge following allergen challenge. 2. To evaluate the effect on bronchial hyper-reactivity in response to AMP challenge. 3. To evaluate the effect on the early asthmatic response (EAR) after allergen challenge. 4. To evaluate the effect on concentrations of exhaled nitric oxide. 5. To assess the safety and tolerability. 6. To evaluate the effect on established markers of inflammation and iNOS activity in blood, BAL and bronchial biopsy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Males and females aged 18 to 55 years inclusive. Women must be of non-childbearing potential. Women will only be considered for inclusion if they have documented proof of hysterectomy or tubal ligation, or meet the criteria for menopause and have been amenorrhoeic for more than 1 year. 2. Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta-agonist therapy by inhalation. 3. Pre-bronchodilator FEV1 >65% of predicted at screening. 4. Documented sensitivity to AMP with a provocative concentration of AMP resulting in a 20% fall in FEV1 (PC20 AMP) of less than 100 mg/mL at screening. 5. Documented sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of <8 mg/mL or provocative dose of methacholine ≤3.2 mg (PD20 methacholine) resulting in a 20% fall in FEV1 at screening. 6. No history of smoking within 6 months of the start of the study, and with a total pack year history of ≤10 pack years. 7. Demonstration of a positive wheal and flare reaction (≥3 mm relative to negative control) to at least one allergen from a battery of allergens (including house dust mite, grass pollen and cat dander) on skin prick testing at screening, or within 12 months of study start. 8. Screening allergen challenge demonstrates that the subject experiences both an early and late asthmatic response. The early asthmatic response must include a fall in FEV1 of ≥20% from the post saline value, on at least one occasion, between 5 and 30 minutes after the final concentration of allergen. The late asthmatic response must include a fall in FEV1 of ≥15% from the post saline value, on at least three occasions, two of which must be consecutive, between 4 and 10 hours after the final concentration of allergen. |
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E.4 | Principal exclusion criteria |
1. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis). 2. Clinically significant abnormalities in safety laboratory analysis at screening. 3. Subject has known history of hypertension or is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP >140mmHg or diastolic BP > 90mmHg. 4. Known hypersensitivity to Singulair. 5. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. 6. History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures. 7. Administration of oral, injectable or dermal steroids within 5 weeks or intranasal and/or inhaled steroids within 1 week of the screening visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Late Asthmatic Response (LAR): minimum FEV1 between 4-10 hours after allergen challenge on Day 14 of each treatment period |
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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 | Yes |
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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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 | 9 |