The efficacy of orally administered GSK2190915 as an add-on to current therapy in subjects with moderate to severe asthma who have elevated sputum neutrophils

Conditions: Moderate to severe asthma
MedDRA version: 9.1Level: LLTClassification code 10001705Term: Allergic asthma

Registration Number: EUCTR2008-007244-33-GB

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 50

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%).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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;Primary end point(s): The numbers of neutrophils in induced sputum (absolute and % count).;Secondary Objective: • To evaluate the effect of treatment on lung function as measured by FEV1<br>• To assess the safety and tolerability of repeat oral doses of GSK2190915<br>• To assess the systemic exposure of GSK2190915 after 12 days repeated doses<br>• To evaluate the effect of treatment on LTE4 in urine and LTB4 in blood and sputum supernatant <br>• To evaluate the effect of treatment on IL-17 in blood <br>• To evaluate the effect of treatment on sputum supernatant including changes in<br> neutrophil elastase, myeloperoxidase and IL-8 <br>• To evaluate effect of treatment on changes in symptoms

Secondary Outcome Measures