E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic asthma |
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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 evaluate the effect of treatment with repeat oral doses of GSK2190915 on the early asthmatic response (EAR) to inhaled allergen in mild asthmatic subjects compared with placebo |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of treatment on the late asthmatic response (LAR) to inhaled allergen. • To assess the safety and tolerability of repeat oral doses of GSK2190915 in mild asthmatic subjects. • To evaluate the effect of treatment on lung function as measured by FEV1. • To evaluate the effect of treatment on concentrations of exhaled nitric oxide. • To evaluate the effect of GSK2190915 on induced sputum. • To evaluate the effect of treatment on bronchial hyper-reactivity. • To evaluate the effect of treatment on LTE4, LTB4 and IgE. • To explore potential PK/PD relationship on EAR and LTE4, LTB4, IgE activity.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females aged 18 to 55 years inclusive. 2. Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2). 3. Female subjects must be of non childbearing potential. 4. Male subjects must agree to use one of the contraception methods listed in Section 8.1 of the protocol. 5. 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. 6. Pre-bronchodilator FEV1 >70% of predicted at screening. 7. Sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of <8 mg/mL at screening. 8. Subjects who are able to produce acceptable induced sputum samples (as defined in the Study procedures Manual). 9. Subjects who are current non-smokers. 10.Demonstration of a positive wheal and flare reaction (> 3 mm relative to negative control) to at least one allergen from a battery of allergens. 11.Screening allergen challenge demonstrates that the subject experiences both an early and late asthmatic response.
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E.4 | Principal exclusion criteria |
1. Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. 2. Clinically significant abnormalities in safety laboratory analysis at screening. 3. Subject has known history of hypertension or is hypertensive at screening. 4. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. 5. 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. 6. Symptomatic with hay fever at screening or predicted to have symptomatic hayfever during the time of study. 7. Administration of oral or injectable steroids within 5 weeks of screening or intranasal and/or inhaled steroids within 4 weeks of the screening visit. 8. Unable to abstain from other medications including non-steroidal anti- inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti- asthma, anti-rhinitis or hay fever medication. 9. If, after 2 concurrent administrations of saline during the allergen challenge at screening the subjects still have a fall in FEV1 of greater than 10%. 10.The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day. 11.History of being unable to tolerate or complete methacholine and/or allergen challenge tests. 12.The subject has a screening QTc value of >450msec, PR interval outside the range 120 to 220msec or an ECG that is not suitable for QT measurements. 13.The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen. 14.The subject has tested positive for HIV antibodies. 15.The subject has a positive pre-study urine cotinine/ breath carbon monoxide test or urine drug or urine or breath alcohol screen.
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E.5 End points |
E.5.1 | Primary end point(s) |
Early Asthmatic Response: minimum FEV1 and weighted mean FEV1 between 0-2 hours after allergen challenge on Day 3 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 | No |
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 | 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 | 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 | 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 | 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 | 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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |