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An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol 100/25 Microgram (mcg) Inhalation Powder, Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Fluticasone Propionate 250 mcg Inhalation Powder in Adults and Adolescents With Persistent Asthma

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ClinicalTrials.gov Identifier: NCT02301975
Recruitment Status : Completed
First Posted : November 26, 2014
Results First Posted : June 12, 2017
Last Update Posted : August 6, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE November 24, 2014
First Posted Date  ICMJE November 26, 2014
Results First Submitted Date  ICMJE May 8, 2017
Results First Posted Date  ICMJE June 12, 2017
Last Update Posted Date August 6, 2018
Study Start Date  ICMJE March 1, 2015
Actual Primary Completion Date November 1, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population [ Time Frame: Baseline and Week 24 ]
    FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the mixed model repeated measures (MMRM) model and least square mean and standard error were calculated. The analysis was performed on ITT Population which comprised of all participants randomized to treatment and who received at least one dose of study medication.
  • Change From Baseline in PM FEV1 Using Per Protocol (PP) Population [ Time Frame: Baseline and Week 24 ]
    FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the MMRM models and least square mean and standard error were calculated. The analysis was performed on PP Population which comprised of all participants in the ITT Population who did not had any full protocol deviations.
Original Primary Outcome Measures  ICMJE
 (submitted: November 24, 2014)
Change from baseline in clinic visit evening (PM) forced expiratory volume in one second (FEV1) (pre-bronchodilator and predose) at the end of the 24-week treatment period [ Time Frame: Baseline and Week 24 ]
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline will be the pre-dose value obtained at the Visit 3 clinic visit. Change from Baseline will be calculated as the Week 24 value minus the Baseline value.
Change History Complete list of historical versions of study NCT02301975 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Change From Baseline in the Percentage of Rescue-free 24-hour Periods [ Time Frame: Baseline and Weeks 1-24 ]
    The number of inhalations of rescue medication used during the day and night were recorded by participants using an electronic diary (e-diary). A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
  • Change From Baseline in the Percentage of Symptom-free 24-hour Periods [ Time Frame: Baseline and Weeks 1-24 ]
    Change from Baseline in the percentage of symptom-free 24 hour period was evaluated. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value.Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
  • Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF) [ Time Frame: Baseline and Weeks 1-24 ]
    PEF was measured using an electric flow meter each morning. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
  • Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20 [ Time Frame: Week 24 ]
    The ACT was a five-item questionnaire developed as a measure of participant's asthma control. The percentage of participants controlled, defined as having ACT score greater than or equal to 20 at the end of Week 24 were analyzed using logistic regression model with covariates of Baseline ACT score, region, sex, age and treatment group.
  • Change From Baseline in PM PEF [ Time Frame: Baseline and Weeks 1-24 ]
    PEF was measured using an electric flow meter each evening. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2014)
  • Change from baseline in the percentage of rescue-free 24-hour periods during the 24-week treatment period [ Time Frame: Baseline and Weeks 1-24 ]
    Subjects will record the number of inhalations of rescue medication used during the day and night in a daily electronic diary (eDiary). A 24 hr period in which a subject's responses to both the morning and evening assessments indicated no rescue medication use will be considered to be a rescue-free 24-hour period. The Baseline value will be derived from the last 7 days of the daily eDiary prior to the randomization of the subject. Change from Baseline will be calculated as the value during the 24-week Treatment Period minus the Baseline value.
  • Change from baseline in the percentage of symptom-free 24-hour periods during the 24-week treatment period [ Time Frame: Baseline and Weeks 1-24 ]
    Asthma symptoms will recorded in a daily eDairy by the subjects every day in the morning and evening. A 24 hr period in which a subject's responses to both the morning and evening assessments indicated no symptoms will be considered to be symptom-free 24-hour period. The Baseline value will be derived from the last 7 days prior to the randomization of the subject. Change from Baseline will be calculated as the value during the 24-week Treatment Period minus the Baseline value.
  • Change from baseline in morning (AM) Peak Expiratory Flow (PEF) averaged over the 24-week treatment period [ Time Frame: Baseline and Weeks 1-24 ]
    PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF will be measured by the subjects using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements will be recorded. Change from Baseline (defined from the last 7 days prior to the randomization of the subject) will be calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value.
  • Percentage of subjects controlled at the end of the 24-week treatment period [ Time Frame: Week 24 ]
    Percentage of subjects controlled will be defined using an Asthma Control Test (ACT) score >=20 at the end of the 24-week treatment period. The ACT is a five-item questionnaire developed as a measure of subject's asthma control that can be quickly and easily completed in clinical practice. The questionnaire will be self-completed by the subjects.
  • Change from baseline in PM PEF averaged over the 24-week treatment period [ Time Frame: Baseline and Weeks 1-24 ]
    PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF will be measured by the subjects using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the last 7 days prior to randomization of the subjects) will be calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol 100/25 Microgram (mcg) Inhalation Powder, Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Fluticasone Propionate 250 mcg Inhalation Powder in Adults and Adolescents With Persistent Asthma
Official Title  ICMJE A Randomized, Double-blind, Double-dummy, Parallel Group, Multicenter Study of Once Daily Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, Twice Daily Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Twice Daily Fluticasone Propionate 250 mcg Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents Already Adequately Controlled on Twice-daily Inhaled Corticosteroid and Long-acting beta2 Agonist
Brief Summary

This study is a randomized, double-blind, double-dummy, parallel group, multicenter, non-inferiority study. The study will enroll adult and adolescent asthmatic subjects who are currently receiving mid dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) (equivalent to fluticasone propionate [FP]/salmeterol 250/50 microgram [mcg]twice daily [BD]), either via a fixed dose combination product or through separate inhalers. The study consists of a LABA washout period of 5 days and a run-in period of 4 weeks, followed by a treatment period of 24 weeks, and a follow up contact period of one week. The total duration of the study is 30 weeks. Approximately 1461 subjects will be randomized to one of the following three treatments (487 per treatment): fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg once daily (OD) in the evening (PM) via ELLIPTA™ inhaler plus placebo BD via ACCUHALER™/DISKUS™; FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler; FP 250 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler. In addition, all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. This study will determine if FF/VI 100/25 mcg OD via ELLIPTA inhaler is non-inferior to FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler in adult and adolescent asthmatic subjects already adequately controlled on a twice-daily ICS/LABA.

SERETIDE, ELLIPTA, ACCUHALER, RELVAR, and DISKUS are trademarks of the GlaxoSmithKline Group of Companies.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Fluticasone Furoate/Vilanterol 100/25 mcg via ELLIPTA inhaler
    FF/Vilanterol 100/25 mcg inhalation powders administered once daily via ELLIPTA inhaler. 30 doses per device and 100/25 mcg per actuation.
  • Drug: Placebo inhalation powders via ELLIPTA inhaler
    Placebo inhalation powders administered once daily via ELLIPTA inhaler. 30 doses per device.
  • Drug: Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler
    FP/Salmeterol 250/50 mcg inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device and 250/50 mcg per actuation.
  • Drug: Placebo inhalation powder via ACCUHALER/DISKUS inhaler
    Placebo inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device.
  • Drug: Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler
    FP 250 mcg inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device and 250 mcg per actuation.
Study Arms  ICMJE
  • Experimental: Fluticasone Furoate/Vilanterol 100/25 mcg
    FF/VI 100/25 mcg by inhalation OD (PM) via ELLIPTA plus placebo by inhalation BD (AM and PM) via ACCUHALER/DISKUS for 24 weeks.
    Interventions:
    • Drug: Fluticasone Furoate/Vilanterol 100/25 mcg via ELLIPTA inhaler
    • Drug: Placebo inhalation powder via ACCUHALER/DISKUS inhaler
  • Experimental: Fluticasone Propionate/Salmeterol 250/50 mcg
    FP/Salmeterol 250/50 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.
    Interventions:
    • Drug: Placebo inhalation powders via ELLIPTA inhaler
    • Drug: Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler
  • Experimental: Fluticasone Propionate 250 mcg
    FP 250 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.
    Interventions:
    • Drug: Placebo inhalation powders via ELLIPTA inhaler
    • Drug: Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler
Publications * Bernstein D, Andersen L, Forth R, Jacques L, Yates L. Once-daily fluticasone furoate/vilanterol versus twice-daily fluticasone propionate/salmeterol in patients with asthma well controlled on ICS/LABA. J Asthma. 2018 Sep;55(9):984-993. doi: 10.1080/02770903.2017.1386214. Epub 2018 Apr 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 16, 2016)
1526
Original Estimated Enrollment  ICMJE
 (submitted: November 24, 2014)
1461
Actual Study Completion Date  ICMJE November 25, 2016
Actual Primary Completion Date November 1, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Subjects must give their signed and dated written informed consent to participate prior to commencing any study related activities.
  • Subjects must be outpatients >=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health, for at least 12 weeks prior to Visit 1 (Note: Countries with local restrictions prohibiting enrollment of adolescents will enroll subjects >=18 years of age only).
  • Subjects may be male or an eligible female. An eligible female is defined as having non-childbearing potential or having childbearing potential and a negative urine pregnancy test at Screening and agrees to use an acceptable method of birth control consistently and correctly.
  • Subjects must have a FEV1 of >=80% of the predicted normal value.
  • Subjects are eligible if they have received mid dose ICS plus LABA (equivalent to FP/salmeterol 250/50 twice daily or an equivalent combination via separate inhalers) for at least the 12 weeks immediately preceding Visit 1.
  • All subjects must be able to replace their current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use, as needed, for the duration of the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits.
  • If in the opinion of the investigator the subject's asthma is well controlled. Exclusion Criteria
  • History of Life-Threatening Asthma, defined for this protocol as an asthma episode that required intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 5 years.
  • Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or in the opinion of the Investigator, expected to affect the subject's asthma status or the subject's ability to participate in the study.
  • Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or resulting in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
  • A subject must not have current evidence of Atlectasis, Bronchopulmonary dysplasia, Chronic bronchitis, Chronic obstructive pulmonary disease, Pneumonia, Pneumothorax, Interstitial lung disease, or any evidence of concurrent respiratory disease other than asthma
  • A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.
  • A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study, whichever is longer of the two.
  • Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of RELVAR™ ELLIPTA inhaler, SERETIDE™ ACCUHALER/DISKUS inhaler or FP 250.
  • History of severe milk protein allergy.
  • Administration of prescription or non-prescription medication that would significantly affect the course of asthma, or interact with study drug.
  • A subject must not be using or require the use of immunosuppressive medications during the study.
  • A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries.
  • Current tobacco smoker or has a smoking history of 10 pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products or inhaled marijuana within the past 3 months (e.g., cigarettes, cigars, electronic cigarettes, or pipe tobacco).
  • A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Brazil,   Czechia,   Germany,   Korea, Republic of,   Mexico,   Netherlands,   Romania,   Spain,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02301975
Other Study ID Numbers  ICMJE 201378
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP