Clinical trial NCT01248975: Safety and Efficacy Study Adding GSK2190915 to Mid-dose Inhaled Corticosteroid/Long Acting Beta Agonist Combination Treatment for Asthma
Official title: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Three-Treatment, Three 6-Week Period Cross-Over, Multi-Center Study to Evaluate the Effect of Adding GSK2190915 300mg as Compared to Adding Montelukast 10mg or Placebo Tablets QD to Fluticasone Propionate/Salmeterol 250/50mcg Diskus BID
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: asthma
GSK2190915
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-11-25
Enrollment: 145
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily in uncontrolled asthmatic subjects \> or = 18 years of age over the course of 6 weeks treatment.

The secondary objectives are to undertake an exploratory analysis of the efficacy and safety of adding montelukast 10mg administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects \> or = 18 years of age over the course of 6 weeks treatment.


Eligibility criteria: Inclusion Criteria:

* Age: 18 years of age or older
* Non-, former or current smokers with a documented smoking history of ≤ 10 pack years
* Asthma diagnosis as defined by the National Institutes of Health
* Best FEV1 of 50% to \<80% of the predicted normal value
* For current and former smokers, a post-albuterol FEV1/FVC ratio of \>0.70 at Visit 1/1a (between 5:00AM and 12:00 noon)
* ≥ 12% and ≥200mL reversibility of FEV1
* Must have been using FP/SAL 250/50mcg inhalation powder BID for at least 2 weeks just prior to Visit 1.
* Must be able to replace their current short-acting beta2-agonists with albuterol inhalation aerosol
* Must be able and willing to give written informed consent to take part in the study.
* Must be able and willing to comply with all aspects of the study including completion of daily e-Diary.

Exclusion criteria:

* History of life-threatening asthma
* Recent asthma exacerbation
* Concurrent respiratory disease
* Recent respiratory infection
* Liver disease
* Other concurrent diseases/abnormalities
* Oral candidiasis
* Drug allergy
* Milk protein allergy
* Immunosuppressive Medications
* Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1
* OATP1B1 substrates within 4 weeks of Visit 1
* Cytochrome P450 3A4 (CYP 3A4) Inhibitors
* Cytochrome P450 3A4 (CYP 3A4) Inducers
* Investigational Medications
* Compliance: any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol
* Affiliation with Investigator's Site

Primary outcomes:
measure: Trough (AM pre-dose and pre-rescue bronchodilator) FEV1
timeFrame: at the end of the 6 week treatment period.
Secondary outcomes:
measure: • Daily trough (AM pre-dose and pre-rescue bronchodilator) AM PEF
timeFrame: averaged over the last 3 weeks of the 6 week treatment period.
measure: • Daily PM PEF
timeFrame: averaged over the last 3 weeks of the 6 week treatment period.
measure: • Daily (average of AM and PM)
timeFrame: averaged over the last 3 weeks of the 6 week treatment period
measure: • Daily asthma symptom score
timeFrame: averaged over the last 3 weeks of the 6 week treatment period.
measure: • Daily rescue salbutamol use
timeFrame: averaged over the last 3 weeks of the 6 week treatment period.
measure: • Percentage of symptom-free days
timeFrame: during the last 3 weeks of the 6 week treatment period.
measure: • Percentage of symptom-free nights
timeFrame: during the last 3 weeks of the 6 week treatment period.
measure: • Percentage of rescue-free days
timeFrame: during the last 3 weeks of the 6 week treatment period.
measure: • Percentage of rescue-free nights
timeFrame: during the last 3 weeks of the 6 week treatment period.
measure: • Percentage of nights without awakenings due to asthma
timeFrame: during the last 3 weeks of the 6 week treatment period.
measure: • Proportion of subjects withdrawn due to lack of efficacy
timeFrame: during the last 3 weeks of the 6 week treatment period.
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: GSK Investigational Site
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Varna
country: Bulgaria
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhia
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Snowise NG, Clements D, Ho SY, Follows RM. Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma. Curr Med Res Opin. 2013 Dec;29(12):1663-74. doi: 10.1185/03007995.2013.842163. Epub 2013 Sep 19.