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The purpose of this study is to determine the safety and usefulness of GSK2190915 in asthmatic patients who develop asthma symptoms following being challenged.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2190915 | Experimental | Intervention |
|
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2190915 - 100mcg | Drug | GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in FEV1% from 0-2 hrs | 0-2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Late Asthmatic Response (LAR): minimum FEV1 and weighted mean FEV1 between 4-10 hours after allergen challenge on Day 3 of each treatment period. | 4 - 10 hours after allergen challenge | |
| Incidence of treatment emergent adverse events. | Duration of Study |
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Inclusion Criteria:
Males and females aged 18 to 55 years inclusive.
Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2).
Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-live post-last dose.
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.
Pre-bronchodilator FEV1 >70% of predicted at screening.
Sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of <8 mg/mL at screening
Subjects who are able to produce acceptable induced sputum samples (as defined in the Study procedures Manual).
Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of ≤10 pack years.
[number of pack years = (number of cigarettes per day/20) x number of years smoked]
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 hair) on skin prick testing at screening, or within 12 months of study start.
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.
Signed and dated written informed consent is obtained from the subject
The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Leiden | 2333 CL | Netherlands | |||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23331559 | Background | Kent SE, Boyce M, Diamant Z, Singh D, O'Connor BJ, Saggu PS, Norris V. The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma. Clin Exp Allergy. 2013 Feb;43(2):177-86. doi: 10.1111/cea.12002. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 111834 | Dataset Specification | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Aug 16, 2017 | |
| Reset | Mar 2, 2018 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Aug 16, 2017 | Mar 2, 2018 |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C552410 | 3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid |
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| Placebo | Drug | Matching Intervention Drug |
|
| Vital signs, ECG, FEV1, Biomarkers(LTE4, LTB4 and IgE) and safety laboratory parameters. | Duration of Study |
| Assessment of FEV1 post-dose on Days 1, 3, (post-dose on Days 3 prior to allergen challenge) and Day 6 of each treatment period. | upto Day 3 |
| Concentration of exhaled nitric oxide post-dose on Day 3, 4 and 6 of each treatment period. | Day 3 - 6 |
| Provocative concentration of methacholine resulting in a 20% reduction in FEV1 (PC20) on Day 4 of each treatment period. | Day 4 |
| Biomarkers (LTE4, LTB4 and IgE) of inflammation in blood, urine and sputum of each treatment period. |
| Assessment of established markers of anti-inflammatory activity in sputum on Day 4 and Day 6. | Day 4 |
| Derived appropriate PK parameters for GSK2190915. | Duration of Study |
| Manchester |
| Lancashire |
| M23 9LT |
| United Kingdom |
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
| GSK Investigational Site | London | W1G 8HU | United Kingdom |
For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111834 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |