Study in Mild Asthmatic Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00748306
First received: September 5, 2008
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

The purpose of this study is to determine the safety and usefulness of GSK2190915 in asthmatic patients who develop asthma symptoms following being challenged.


Condition Intervention Phase
Asthma
Drug: GSK2190915 - 100mcg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change in FEV1% from 0-2 hrs [ Time Frame: 0-2 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Late Asthmatic Response (LAR): minimum FEV1 and weighted mean FEV1 between 4-10 hours after allergen challenge on Day 3 of each treatment period. [ Time Frame: 4 - 10 hours after allergen challenge ] [ Designated as safety issue: No ]
  • Incidence of treatment emergent adverse events. [ Time Frame: Duration of Study ]
  • Vital signs, ECG, FEV1, Biomarkers(LTE4, LTB4 and IgE) and safety laboratory parameters. [ Time Frame: 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. [ Time Frame: upto Day 3 ]
  • Concentration of exhaled nitric oxide post-dose on Day 3, 4 and 6 of each treatment period. [ Time Frame: Day 3 - 6 ]
  • Provocative concentration of methacholine resulting in a 20% reduction in FEV1 (PC20) on Day 4 of each treatment period. [ Time Frame: 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. [ Time Frame: Day 4 ]
  • Derived appropriate PK parameters for GSK2190915. [ Time Frame: Duration of Study ]

Enrollment: 19
Study Start Date: December 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2190915
Intervention
Drug: GSK2190915 - 100mcg
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor
Other Name: GSK2190915
Placebo Comparator: Placebo Drug: Placebo
Matching Intervention Drug

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748306

Locations
Netherlands
GSK Investigational Site
Leiden, Netherlands, 2333 CL
United Kingdom
GSK Investigational Site
Manchester, Lancashire, United Kingdom, M23 9LT
GSK Investigational Site
London, United Kingdom, W1G 8HU
GSK Investigational Site
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00748306     History of Changes
Other Study ID Numbers: 111834
Study First Received: September 5, 2008
Last Updated: March 22, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
challenge
early asthmatic response
mild asthmatics
Allergen
methacholine

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 22, 2014