Study in Mild Asthmatic Patients

NCT ID: NCT00748306

Last Updated: 2016-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2009-09-30

Brief Summary

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

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

GSK2190915

Intervention

Group Type: EXPERIMENTAL

GSK2190915 - 100mcg

Intervention Type: DRUG

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching Intervention Drug

Interventions

GSK2190915 - 100mcg

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor

Intervention Type: DRUG

Placebo

Matching Intervention Drug

Intervention Type: DRUG

Other Intervention Names

GSK2190915

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Leiden, , Netherlands

GSK Investigational Site

Manchester, Lancashire, United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

Netherlands; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 23331559 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

111834

Identifier Type: -

Identifier Source: org_study_id