Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01498653
First received: December 21, 2011
Last updated: February 13, 2014
Last verified: January 2014
  Purpose

A randomised, double-blind, double-dummy, parallel group study to evaluate the efficacy and safety of fluticasone furoate/vilanterol trifenatate (FF/VI) inhalation powder delivered once daily in the treatment of asthma in adolescent and adult subjects of Asian ancestry currently treated with high-strength inhaled corticosteroids or mid-strength ICS/LABA combination therapy


Condition Intervention Phase
Asthma
Drug: GW685698/GW642444
Drug: CCI18781
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Double-dummy, Parallel Group Study to Evaluate the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate (FF/VI) Inhalation Powder Delivered Once Daily Compared to Fluticasone Propionate Delivered Twice Daily in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry Currently Treated With High-strength Inhaled Corticosteroids or Mid-strength ICS/LABA Combination Therapy.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline (BL) in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 (up to Day 84) ] [ Designated as safety issue: No ]
    Peak Expiratory Flow is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using Analysis of Covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment.


Secondary Outcome Measures:
  • Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period [ Time Frame: Baseline and Weeks 1-12 (up to Day 84) ] [ Designated as safety issue: No ]
    PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

  • Mean 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 (up to Day 84) ] [ Designated as safety issue: No ]
    The number of inhalations of rescue albuterol/salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night was recorded by the participants in a daily diary. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 12-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

  • Mean 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 (up to Day 84) ] [ Designated as safety issue: No ]
    Asthma symptoms were recorded in a daily dairy by the participants every day in the morning and evening before taking any rescue or study medication and before PEF measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered as symptom free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Participants who were symptom free for 24-hour periods during the 12-week Treatment Period were assessed. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

  • Change From Baseline in Total Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The AQLQ is a disease-specific, self-administered quality of life questionnaire developed to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). The 32 items of the questionnaire are averaged to produce one overall quality of life score. The response format consists of a 7-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.


Enrollment: 313
Study Start Date: January 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FF/VI 200/25mcg once daily
ICS/LABA
Drug: GW685698/GW642444
ICS/LABA
Active Comparator: Fluticasone propionate 500mcg twice daily
ICS
Drug: CCI18781
ICS

Detailed Description:

This will be a randomized, double-blind, active-comparator, parallel group, multi-center study. At Visit 1 (Screening Visit) subjects who meet all of the inclusion criteria and none of the exclusion criteria will enter a two week Run-in period. Subjects will remain on their current ICS therapy throughout the Run-in period. At the end of the Run-in period (Visit 2) subjects meeting the randomization criteria will enter a 12 week treatment period and receive one of the two following treatments: 1) FF (200mcg)/VI (25mcg) administered once daily in the evening via a Novel Dry Powder Inhaler (NDPI) 2) Fluticasone propionate 500mcg administered twice daily via DISKUS™ Inhaler In addition, all subjects will be supplied with albuterol/salbutamol inhalation aerosol to be used as required to treat asthma symptoms.

Subjects who have not met the randomization criteria at Visit 2 will be withdrawn from the study.

Subjects meeting the randomization criteria will be randomized to one of the two treatment groups and will attend the clinic for 3 on-treatment visits at Week 4 (Visit 3), Week 8 (Visit 4) and Week 12 (Visit 5). Subjects will receive treatment for 12 weeks. A Follow-up Visit or Contact (Visit 6) will take place 1 week after completing study medication. All clinic visits will take place in the morning. Subjects will participate in the study for a maximum of 15 weeks (Screening to Follow-up inclusive). A subject is regarded to have completed the study if they complete all phase of the study (Screening, treatment, Follow-up).

  Eligibility

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

Inclusion Criteria:

  1. Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study
  2. Type of Subject: Outpatients, of Asian ancestry, 12 years of age or older at Visit 1 (or ≥18 years of age or older if local regulations or the regulatory status of study medication permit enrolment of adults only) with a diagnosis of asthma as defined by the Global Initiative for Asthma [GINA, 2009] at least 12 weeks prior to Visit 1.
  3. Gender: Male or Eligible Female, defined as non-childbearing potential or childbearing potential using an acceptable method of birth control consistently and correctly
  4. Severity of Disease: A best FEV1 of 40%-90% of the predicted normal value at the Visit 1 Screening visit. Predicted values will be based upon NHANES III using the Asian adjustment
  5. Reversibility of Disease: Demonstrated ≥12% and ≥200mL reversibility of FEV1 within 10-40minutes following 2-4 inhalations of albuterol/salbutamol inhalation aerosol (or one nebulized treatment with albuterol/salbutamol solution) at the Screening Visit.
  6. Current Anti-Asthma Therapy: All subjects must be using an ICS, with or without LABA, for at least 12 weeks prior to Visit 1.
  7. Short-Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol 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 4 hours prior to study visits.

Exclusion Criteria:

  1. History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 10 years.
  2. Respiratory Infection: 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, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
  3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
  4. Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
  5. Other Concurrent Diseases/Abnormalities: A subjects must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
  6. Oropharyngeal Examination: A subject will not be eligible for the Run-in if he/she has clinical visual evidence of candidiasis at Visit 1.
  7. Allergies:

    • Drug Allergy: 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 the new powder inhaler
    • Milk Protein Allergy: History of severe milk protein allergy.
  8. Concomitant Medications: Use of the protocol defined prohibited medications within the prohibited time intervals prior to Screening (Visit 1) or during the study.
  9. Tobacco Use: Current smoker or a smoking history of 10 pack years (e.g., 20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, smokeless or pipe tobacco).
  10. Affiliation with Investigator's Site: 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.
  11. Previous Participation: A subject may not have previously been randomized to treatment in another Phase III FF/VI combination product study
  12. Compliance: 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
  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: NCT01498653

Locations
China, Guangdong
GSK Investigational Site
Guangzhou, Guangdong, China, 510120
China, Hunan
GSK Investigational Site
Changsha, Hunan, China, 410011
China, Liaoning
GSK Investigational Site
Shenyang, Liaoning, China, 110001
GSK Investigational Site
Shenyang, Liaoning, China, 110015
China
GSK Investigational Site
Beijing, China, 100020
GSK Investigational Site
Beijing, China, 100191
GSK Investigational Site
Beijing, China, 100029
GSK Investigational Site
Chongqing, China, 400038
GSK Investigational Site
Chongqing, China, 400037
GSK Investigational Site
Shanghai, China, 200025
GSK Investigational Site
Shanghai, China, 200080
GSK Investigational Site
Shanghai, China, 200032
Korea, Republic of
GSK Investigational Site
Bucheon-si, Gyeonggi-Do, Korea, Republic of, 420-767
GSK Investigational Site
Cheongju, Chungcheongbuk-do, Korea, Republic of, 361-711
GSK Investigational Site
Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 411706
GSK Investigational Site
Pusan, Korea, Republic of, 602-739
GSK Investigational Site
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
GSK Investigational Site
Seoul, Korea, Republic of, 130-709
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 137-701
GSK Investigational Site
Seoul, Korea, Republic of, 152-703
GSK Investigational Site
Seoul,, Korea, Republic of, 120-752
Philippines
GSK Investigational Site
Lipa City, Philippines, 4217
GSK Investigational Site
Quezon City, Philippines, 1100
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01498653     History of Changes
Other Study ID Numbers: 113714
Study First Received: December 21, 2011
Results First Received: September 19, 2013
Last Updated: February 13, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)
China: Food and Drug Administration
Philippines: Department of Health

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

ClinicalTrials.gov processed this record on October 16, 2014