E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe asthma |
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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 number of neutrophils in induced sputum in moderate to severe asthmatic subjects compared with placebo |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of treatment on lung function as measured by FEV1 • To assess the safety and tolerability of repeat oral doses of GSK2190915 • To assess the systemic exposure of GSK2190915 after 12 days repeated doses • To evaluate the effect of treatment on LTE4 in urine and LTB4 in blood and sputum supernatant • To evaluate the effect of treatment on IL-17 in blood • To evaluate the effect of treatment on sputum supernatant including changes in neutrophil elastase, myeloperoxidase and IL-8 • To evaluate effect of treatment on changes in symptoms |
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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 65 years inclusive. 2. Body mass index within the range 18.5-37.0 kilograms/metre2 (kg/m2). 3. An established clinical history of Asthma in accordance with the definition by the GINA Guidelines [GINA, 2006]. 4. Female subjects of childbearing and non childbearing potential 5. Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 3 months after the last dose. 6. Subject with moderate to severe asthma with a post bronchodilator FEV1 >/=50% of predicted for age and height. 7. Subject who are on regular inhaled corticosteroids without or in combination with a regular long acting Beta 2 Agonist. The dose should be stable for at least 4 weeks before screening. 8. Subjects who are taking a minimum of FP 250mg BID or equivalent 9. Persistent sputum neutrophilia defined by sputum neutrophils ≥ 65% with TTC < 15 million cells/g with no evidence of eosinophilia (sputum eosinophils < 2%).
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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 uncontrolled hypertension or is hypertensive at screening. 4. History of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a four week period before the screening visit. 5. History of life-threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures. 6. Subject is unable to abstain from taking prescription or non-prescription drugs unless in the opinion of the Investigator and sponsor the medication will not interfere with the study. 7. Administration of oral or injectable steroids within 6 weeks of screening. 8. Administration of anti -leukotrienne therapies for 14 days before screening and during the study. 9. Subject is undergoing allergen desensitisation therapy. 10. Administration of OATP1B1 substrates from 2 weeks before dosing, and until all follow up assessments are completed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The numbers of neutrophils in induced sputum (absolute and % count). |
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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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |