Safety and Efficacy Study Adding GSK2190915 to Mid-dose Inhaled Corticosteroid/Long Acting Beta Agonist Combination Treatment for Asthma

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: FP/SAL 250/50mcg BID; Drug: GSK2190915 200mg QD (AM); Drug: GSK2190915 100mg QD (AM); Drug: Placebo capsule (PM); Drug: Montelukast 10mg QD (PM); Drug: Placebo tablets (2) (AM)

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • GSK Investigational Site
  • Ruse, Bulgaria, 7000
    • GSK Investigational Site
  • Varna, Bulgaria, 9010
    • GSK Investigational Site
• Poland
  • Bialystok, Poland, 15-084
    • GSK Investigational Site
  • Lodz, Poland, 93-329
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49051
    • GSK Investigational Site
  • Dnipropetrovsk, Ukraine, 49027
    • GSK Investigational Site
  • Donetsk, Ukraine, 83099
    • GSK Investigational Site
  • Ivano-Frankivsk, Ukraine, 76018
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61037
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61035
    • GSK Investigational Site
  • Kiev, Ukraine, 03680
    • GSK Investigational Site
  • Kiev, Ukraine, 3680
    • GSK Investigational Site
  • Kyiv, Ukraine, 02091
    • GSK Investigational Site
  • Kyiv, Ukraine, 02232
    • GSK Investigational Site
  • Kyiv, Ukraine, 03115
    • GSK Investigational Site
  • Kyiv, Ukraine, 04107
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69035
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)	Drug: FP/SAL 250/50mcg BID; FP/SAL 250/50mcg BID; Drug: GSK2190915 200mg QD (AM); GSK2190915 200mg QD (AM); Drug: GSK2190915 100mg QD (AM); GSK2190915 100mg QD (AM); Drug: Placebo capsule (PM); Placebo capsule (PM)
Active Comparator: FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)	Drug: FP/SAL 250/50mcg BID; FP/SAL 250/50mcg BID; Drug: Montelukast 10mg QD (PM); Montelukast 10mg QD (PM); Drug: Placebo tablets (2) (AM); Placebo tablets (2) (AM)
Placebo Comparator: FP/SAL 250/50mcg BID plus placebo BID; P/SAL 250/50mcg BID plus placebo BID	Drug: FP/SAL 250/50mcg BID; FP/SAL 250/50mcg BID; Drug: Placebo capsule (PM); Placebo capsule (PM); Drug: Placebo tablets (2) (AM); Placebo tablets (2) (AM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Trough (AM pre-dose and pre-rescue bronchodilator) FEV1	at the end of the 6 week treatment period.

Secondary Outcome Measures

Outcome Measure	Time Frame
• Daily trough (AM pre-dose and pre-rescue bronchodilator) AM PEF	averaged over the last 3 weeks of the 6 week treatment period.
• Daily PM PEF	averaged over the last 3 weeks of the 6 week treatment period.
• Daily (average of AM and PM)	averaged over the last 3 weeks of the 6 week treatment period
• Daily asthma symptom score	averaged over the last 3 weeks of the 6 week treatment period.
• Daily rescue salbutamol use	averaged over the last 3 weeks of the 6 week treatment period.
• Percentage of symptom-free days	during the last 3 weeks of the 6 week treatment period.
• Percentage of symptom-free nights	during the last 3 weeks of the 6 week treatment period.
• Percentage of rescue-free days	during the last 3 weeks of the 6 week treatment period.
• Percentage of rescue-free nights	during the last 3 weeks of the 6 week treatment period.
• Percentage of nights without awakenings due to asthma	during the last 3 weeks of the 6 week treatment period.
• Proportion of subjects withdrawn due to lack of efficacy	during the last 3 weeks of the 6 week treatment period.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: November 24, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimate): November 25, 2010

Study Record Updates

• Last Update Posted (Estimate): November 25, 2016
• Last Update Submitted That Met QC Criteria: November 23, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: asthma; GSK2190915
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 114387

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 114387
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register