An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol (FF/VI) 200/25 Microgram (mcg) , FF/VI 100/25 mcg, and FF 100 mcg in Adults and Adolescents With Persistent Asthma.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01686633
First received: September 13, 2012
Last updated: July 10, 2014
Last verified: May 2014
  Purpose

This is a Phase III, multicenter, randomized, double-blind, stratified, parallel-group study with three active comparators in subjects with moderate to severe persistent asthma. The study consists of a run-in period of 4 weeks, followed by a treatment period of 12 weeks, and a follow up contact period of one week. The total duration of the study is 17 weeks. 990 subjects will be randomized to one of three treatments (FF/VI Inhalation Powder 200/25 mcg once daily in the evening; FF/VI Inhalation Powder 100/25 mcg once daily in the evening; FF 100 Inhalation Powder once daily in the evening) for 12 weeks. In addition, all subjects will be supplied albuterol/salbutamol inhalation aerosol at Visit 1 to use as needed for acute asthma symptoms throughout the entire study. Subjects will attend four on-treatment visits at Weeks 2, 4, 8, and 12 (Visits 4 through 7).


Condition Intervention Phase
Asthma
Drug: Fluticasone Furoate/ Vilanterol 200/25 mcg
Drug: Fluticasone Furoate/ Vilanterol 100/25 mcg
Drug: Fluticasone Furoate 100 mcg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Parallel Group, Multicenter Study of Fluticasone Furoate/Vilanterol 200/25 mcg Inhalation Powder, Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, and Fluticasone Furoate 100 mcg Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in Weighted Mean Forced Expiratory Volume in One Second (FEV1) Over 0 to 24 Hours Post-dose at the End of the 12-week Treatment Period [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 (within 30 minutes prior to dosing) and post-dose FEV1 measurements at 5, 15, and 30 minutes and at 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours on Day 84/Week 12. At each time point, the highest of three technically acceptable measurements was recorded. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 84/Week 12 minus the Baseline value. Baseline was the pre-dose FEV1 measurement value obtained at Visit 3. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline FEV1, region, sex, age, and treatment.


Secondary Outcome Measures:
  • Change From Baseline in Clinic Visit Trough FEV1 at the End of the 12-week Treatment Period [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as a pre-dose FEV1 measurement taken at a clinic visit while still on-treatment. Change from Baseline in trough FEV1 at the end of the 12-week treatment period was defined using the 24-hour post-dose serial FEV1 measurement taken at the Week 12 clinic visit. Change from Baseline was calculated as the Week 12 trough FEV1 value minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline trough FEV1, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.

  • Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 ] [ Designated as safety issue: No ]
    The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily electronic diary (eDiary). 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

  • Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 ] [ Designated as safety issue: No ]
    Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

  • Change From Baseline in Daily Morning (AM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 ] [ Designated as safety issue: No ]
    Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants 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 and each morning. The best of three measurements was recorded. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

  • Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 ] [ Designated as safety issue: No ]
    PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants 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 and each morning. The best of three measurements was recorded. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.


Enrollment: 1040
Study Start Date: September 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm1: Fluticasone Furoate/ Vilanterol 200/25 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF/ VI 200/25 mcg once daily in the evening for 84 days.
Drug: Fluticasone Furoate/ Vilanterol 200/25 mcg
Fluticasone furoate/ vilanterol will be available as 200/25 mcg Novel dry powder inhaler (NDPI) with 30 doses per device and 200/25 mcg per actuation
Experimental: Arm 2: Fluticasone Furoate/ Vilanterol 100/25 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF/ VI 100/25 mcg once daily in the evening for 84 days
Drug: Fluticasone Furoate/ Vilanterol 100/25 mcg
Fluticasone furoate/ vilanterol will be available as 100/25 mcg NDPI with 30 doses per device and 100/25 mcg per actuation
Experimental: Arm 3: Fluticasone Furoate 100 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF 100 mcg once daily in the evening for 84 days
Drug: Fluticasone Furoate 100 mcg
Fluticasone furoate will be available as 100 mcg NDPI with 30 doses per device and 100/25 mcg per actuation

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must give their signed and dated (written) informed consent to participate. Written informed consent must be obtained if a subject's current medication is changed as a result of study participation
  • Outpatient >=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health. Countries with local restrictions prohibiting enrolment of adolescents will only enroll subjects >=18 years of age
  • Male or an eligible female. Eligible female is defined as having non-childbearing potential or having childbearing potential and using an acceptable method of birth control consistently and correctly.
  • Best pre-bronchodilator FEV1 of 40% to 80% of their predicted normal value.
  • Demonstrate >=12% and >=200 mL reversibility of FEV1 within 10 to 40 minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (or an equivalent nebulized treatment with albuterol/salbutamol solution) or have documented reversibility testing within the 6 months prior to Visit 1 meeting this measure of reversibility. A spacer device may be used for testing, if required.
  • If subject have received ICS for at least 12 weeks prior to Visit 1 and their treatment during the 4 weeks immediately prior to Visit 1 consisted of either of the two regimens (a or b).a.) A stable mid-dose or high-dose of ICS alone (e.g., >=FP 250 mcg twice daily) or b.) A stable dose of a mid-dose ICS/LABA combination (e.g., FP/Salmeterol [SALM] 250/50 mcg twice daily) or an equivalent combination via separate inhalers.
  • Use of ICS/LABA are not permitted with LABA on the day of Visit 1.
  • Must be able to replace current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, during the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits

Exclusion Criteria:

  • History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
  • 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 that required oral corticosteroids within the 12 weeks prior to Visit 1 or, resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
  • A subject must not have current evidence of atelectasis (segmental or larger), bronchopulmonary dysplasia, chronic obstructive pulmonary 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 efficacy results if the condition/disease exacerbated during the study
  • Chronic stable hepatitis B or C are acceptable provided their screening alanine transaminase (ALT) is <2x upper limit of normal (ULN) and the y otherwise meet the entry criteria. Chronic co-infection with both hepatitis B and hepatitis C are not eligible
  • Clinical visual evidence of candidiasis at Visit 1
  • Use of any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½), whichever is longer of the two.
  • Allergies to drug or milk protein: any adverse reaction, to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or known or suspected sensitivity to the constituents of the NDPI, or history of severe milk protein allergy
  • Administration of medication that would significantly affect the course of asthma, or interact with study drug
  • Use of immunosuppressive medications during the study.
  • Use of potent CYP3A4 inhibitor within 4 weeks of Visit 1.
  • A subject or his/her parent or legal guardian has any infirmity, disability, disease, or resides in a 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 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 within the past 3 months (i.e., cigarettes, cigars, or pipe tobacco).
  • If subject is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
  • Subject previously randomized to treatment with FF/VI or FF in another Phase III study
  • Subjects working on night shift a week prior to Visit 1 or during the study period.
  • Adolescents who are wards of the state or government
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686633

  Show 137 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01686633     History of Changes
Other Study ID Numbers: 116863
Study First Received: September 13, 2012
Results First Received: April 3, 2014
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
asthma
pharmacogenetics
adult
vilanterol
adolescents
fluticasone furoate

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014