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Safety and Efficacy Study of Adding GSK2190915 to Low Dose Inhaled Corticosteroid Treatment for Asthma Subjects > or = 12 Years of Age

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01156792
First Posted: July 5, 2010
Last Update Posted: April 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 100mg, GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate 100mcg inhalation administered twice daily in uncontrolled asthmatic subjects > or = 12 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 or salmeterol 50mcg administered twice daily to fluticasone propionate 100mcg inhalation administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects > or = 12 years of age over the course of 6 weeks treatment.


Condition Intervention Phase
Asthma Drug: FP 100 Drug: GSK2190915 100 Drug: GSK2190915 300 Drug: montelukast Drug: placebo Drug: FP/SAL 100/50 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Five-Treatment, Four 6-Week Period Cross-Over, Multi-Center Study to Evaluate the Effect of Adding GSK2190915 100mg, GSK2190915 300mg, Montelukast 10mg or Placebo Tablets Once Daily or Salmeterol 50mcg Inhalation Powder Twice Daily to Fluticasone Propionate 100mcg Inhalation Powder Twice Daily in Uncontrolled Asthmatic Subjects ≥ 12 Years of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period [ Time Frame: End of Week 6 ]
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically using spirometry, prior to study medication and any rescue albuterol (bronchodilator) use. At the end of the 6-week treatment period, FEV1 was measured approximately 24 hours after the participant's last morning dose of study medication and approximately 12 hours after the evening dose of study medication. Trough FEV1 was analyzed using mixed effect analysis of covariance (ANCOVA) model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effect of participant. Intent-to-Treat Population is defined as all participants who were randomized and received at least one dose of study drug.


Secondary Outcome Measures:
  • Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    The PEF is a measure of lung function and measures how fast a person can breathe out. Trough PEF was measured every morning prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily electronic diary (eDiary). Daily trough morning PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups [ Time Frame: Week 4 to Week 6 ]
    The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every morning and evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily average of morning and evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. This outcome measure explored the efficacy between GSK2190915 and montelukast due to the dosing time difference.

  • Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Daytime and night time asthma symptoms were recorded every evening at bedtime and every morning upon rising, respectively, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on scales ranging from '0' (implying no symptoms) to either 5 (for daytime symptoms) or 4 (for night time symptoms) (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. 24-hour period asthma symptom scores were averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    A SABA (albuterol) was provided to participants as a rescue medication, to use as needed for symptomatic relief of asthma symptoms. Participants were required to record their albuterol use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The daily rescue SABA use was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Daytime asthma symptoms were recorded every evening at bedtime, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 6-point scale ranging from '0' (implying no symptoms) to 5 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of days when symptoms were not experienced ("symptom-free days") during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale ranging from '0' (implying no symptoms) to 4 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of nights when symptoms were not experienced ("symptom-free nights") during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of days when rescue medication was not used ("rescue-free days") during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of nights when rescue medication was not used ("rescue-free nights") during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale: 0 = no symptoms during the night, 1 = symptoms causing to wake once, 2 = symptoms causing to wake twice or more, 3 = symptoms causing to be awake most of the night, 4 = could not sleep due to severe symptoms. Participants recorded the symptoms in a daily eDiary. The number of nights with no awakenings due to asthma during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.

  • Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period [ Time Frame: Week 4 to Week 6 ]
    Participants were withdrawn if they met any of the following three criteria for 'lack of efficacy': 1) Clinic FEV1 below the FEV1 'Stability Limit' value, 2) During any consecutive 7-day period, the participant experienced PEF fallen below the PEF 'Stability Limit' for more than 3 days, or if >= 12 inhalations per day of albuterol were used for more than 2 days, and 3) Ashtma exacerbation. The number of withdrawals due to lack of efficacy were summarized for each treatment and Fisher's Exact test was used for comparison with placebo add-on. Withdrawals occurring during active washout periods are not included.


Enrollment: 162
Study Start Date: September 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FP 100mcg BID plus GSK2190915 100mg QD (AM)
FP 100mcg BID plus GSK2190915 100mg QD (AM)
Drug: FP 100
FP 100mcg BID
Drug: GSK2190915 100
GSK2190915 100mg QD (AM)
Experimental: FP 100mcg BID plus GSK2190915 300mg QD (AM)
FP 100mcg BID plus GSK2190915 300mg QD (AM)
Drug: FP 100
FP 100mcg BID
Drug: GSK2190915 300
GSK2190915 300mg QD (AM)
Active Comparator: FP 100mcg BID plus montelukast 10mg QD (PM)
FP 100mcg BID plus montelukast 10mg QD (PM)
Drug: FP 100
FP 100mcg BID
Drug: montelukast
montelukast 10mg QD (PM)
Active Comparator: FP 100mcg BID plus placebo BID
FP 100mcg BID plus placebo BID
Drug: FP 100
FP 100mcg BID
Drug: placebo
placebo BID
Active Comparator: FP/SAL 100/50mcg BID plus placebo BID
FP/SAL 100/50mcg BID plus placebo BID
Drug: placebo
placebo BID
Drug: FP/SAL 100/50
FP/SAL 100/50mcg BID

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 12 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
  • 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 100mcg 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01156792


  Show 32 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 114255
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01156792     History of Changes
Other Study ID Numbers: 114255
First Submitted: July 1, 2010
First Posted: July 5, 2010
Results First Submitted: December 8, 2016
Results First Posted: February 3, 2017
Last Update Posted: April 5, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
asthma
GSK2190915

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action