EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomised, double-blind, placebo-controlled, 2-period cross-over study to evaluate the effect of treatment with GSK2190915 on the allergen-induced asthmatic response in subjects with mild asthma
Trial description: The purpose of this study is to determine the safety and usefulness of GSK2190915 in asthmatic patients who develop asthma symptoms following being challenged.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Minimum Forced Expiratory Volume in 1 second (FEV1) and weighted mean FEV1 between 0-2 hours after allergen challenge on Day 3 of each treatment period
Timeframe: Baseline (Day 1 Pre-dose) and 0-2 hours on Day 3 of each treatment period
Secondary outcomes:
Minimum FEV1 and weighted mean FEV1 between 4-10 hours after allergen challenge on Day 3 of each treatment period
Timeframe: Baseline (Day 1 Pre-dose) and 4-10 hours after allergen challenge on Day 3 of each treatment period
Number of participants with treatment emergent Adverse Events (AEs)
Timeframe: Up to 99 days
Number of participants with Vital Signs of Potential Clinical Importance
Timeframe: Up to follow-up (approximately up to 47 days from first dose)
Number of participants with electrocardiogram (ECG) values of Potential Clinical Importance
Timeframe: Up to follow-up (approximately up to 47 days from first dose)
Absolute Change in Allergen Challenge FEV1 from Saline Baseline on Day 3
Timeframe: Baseline (Day 1, Pre-dose ) and 5, 10 , 15, 20, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 and 10 hours on Day 3
Non-Challenge FEV1 at Day 1, 3, 6
Timeframe: Day 1, 3 and 6 (Day 5 at 24 hour)
Absolute Change from Baseline in Pre-Challenge FEV1 on Day 1, Day 3 and Day 6 (24 hour post-dose on Day 5)
Timeframe: Baseline(Day 1, pre-dose) and Day 1, Day 3 and Day 6 (24 hour post-dose on Day 5)
Number of participants with Clinical Chemistry Abnormalities of Potential Clinical Importance
Timeframe: Up to follow-up (approximately up to 47 days from first dose)
Number of participants with Hematology Abnormalities of Potential Clinical Importance
Timeframe: Up to follow-up (approximately up to 47 days from first dose)
Concentration of exhaled nitric oxide (NO) on Day 3, 4 and 6 of each treatment period
Timeframe: Day 3, 4 and 6 (Day 5 at 24 hours)
Provocative concentration of methacholine resulting in a 20 percent (%) reduction in FEV1 (PC20) on Day 4 of each treatment period
Timeframe: Day 4 of each treatment period
Percentage Change from Baseline for Plasma Leukotriene B4 (LTB4)
Timeframe: Baseline (Day 1 pre-dose) and Day 3 (1 and 12 hour)of each treatment period
Percentage Change from Baseline for Urine Leukotriene E4 (LTE4)
Timeframe: Baseline (Day 1 Pre-dose) and Day 3 (pre-dose 1, 0-2 and 0-3 hour) and Day 4 (pre-dose 1)
Mean plasma Immunoglobulin E (IgE)
Timeframe: Day 1 (pre-dose 1), Day 3 (pre-dose 1) and Day 6 (Day 5 at 24 hour)
Assessment of established markers of anti-inflammatory activity in sputum on Day 4 and Day 6
Timeframe: Day 4 and Day 6
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration AUC(0-t) for GSK2190915
Timeframe: Day 3 of each treatment period
Maximum observed concentration (Cmax) for GSK2190915
Timeframe: Day 3 of each treatment period
Time of occurrence of Cmax (tmax) for GSK2190915
Timeframe: Day 3 of each treatment period
Interventions:
Enrollment:
20
Primary completion date:
2009-03-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
S Kent, M Boyce, Z Diamont, D Singh, B O’Connor, P Saggu, V Norris. The 5-lipoxygenase activating protein inhibitor, GSK2190915, attenuates allergen induced asthmatic response in subjects with mild asthma: a randomized, double-blind, placebo controlled two-period cross over study. Clin Exp Allergy. 2013;43:177-186.
S Kent, M Boyce, Z Diamont, D Singh, B O’Connor, P Saggu, V Norris.The 5-lipoxygenase activating protein inhibitor, GSK2190915, attenuates allergen induced asthmatic response in subjects with mild asthma: a randomized, double-blind, placebo controlled two-period cross over study.Clin Exp Allergy.2013;43:177-186.
Medical condition
Asthma
Product
fiboflapon
Collaborators
Not applicable
Study date(s)
December 2008 to September 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
No
- 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).
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 1. Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, 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).
Inclusion and exclusion criteria
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 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. 4. 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. 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 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] 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 (including house dust mite, grass pollen and cat hair) on skin prick testing at screening, or within 12 months of study start. 11. 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. 12. Signed and dated written informed consent is obtained from the subject 13. 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: 1. Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, 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 >150 mmHg or diastolic BP > 90mmHg. 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 hypercapnia, 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, other than short acting inhaled beta-agonists and paracetamol (up to 4 g per day) for the treatment of minor ailments eg headache from 14 days before screening until the follow-up visit. 9. Unable to abstain from short acting beta agonists as described in the restrictions section. 10. 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%. 11. 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. 12. History of being unable to tolerate or complete methacholine and/or allergen challenge tests. 13. Subject is undergoing allergen desensitisation therapy. 14. There is a risk of non-compliance with study procedures. 15. History of blood donation (500 mL) within 3 months of starting the clinical study. 16. The subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. One unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one measure (25 ml) of spirits. 17. 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 (e.g. poorly defined termination of the T-wave). 18. The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen. 19. The subject has tested positive for HIV antibodies. 20. The subject has a positive pre-study urine cotinine/ breath carbon monoxide test or urine drug or urine or breath alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
Trial location(s)
Location
GSK Investigational Site
Manchester, Lancashire, United Kingdom, M23 9LT
Status
Will Be Recruiting
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2009-03-09
Actual study completion date
2009-03-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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