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
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02301975
Collaborator
(none)
1,526
179
3
20.9
8.5
0.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1526 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date
:
Mar 1, 2015
Actual Primary Completion Date
:
Nov 1, 2016
Actual Study Completion Date
:
Nov 25, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
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 powder via ACCUHALER/DISKUS inhaler
Placebo inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device.
|
| 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. |
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.
|
| 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. |
Drug: Placebo inhalation powders via ELLIPTA inhaler
Placebo inhalation powders administered once daily via ELLIPTA inhaler. 30 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.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population [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 [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.
Secondary Outcome Measures
- Change From Baseline in the Percentage of Rescue-free 24-hour Periods [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 [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) [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 [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 [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Huntington Beach | California | United States | 92647 |
| 2 | GSK Investigational Site | Riverside | California | United States | 92506 |
| 3 | GSK Investigational Site | Rolling Hills Estates | California | United States | 90274 |
| 4 | GSK Investigational Site | San Diego | California | United States | 92103 |
| 5 | GSK Investigational Site | Upland | California | United States | 91786 |
| 6 | GSK Investigational Site | Denver | Colorado | United States | 80230 |
| 7 | GSK Investigational Site | Miami | Florida | United States | 33165 |
| 8 | GSK Investigational Site | Miami | Florida | United States | 33174 |
| 9 | GSK Investigational Site | Albany | Georgia | United States | 31707 |
| 10 | GSK Investigational Site | Baltimore | Maryland | United States | 21236 |
| 11 | GSK Investigational Site | Columbia | Maryland | United States | 21044 |
| 12 | GSK Investigational Site | Minneapolis | Minnesota | United States | 55402 |
| 13 | GSK Investigational Site | Plymouth | Minnesota | United States | 55441 |
| 14 | GSK Investigational Site | Columbia | Missouri | United States | 65203 |
| 15 | GSK Investigational Site | Rolla | Missouri | United States | 65401 |
| 16 | GSK Investigational Site | Bellevue | Nebraska | United States | 68123-4303 |
| 17 | GSK Investigational Site | Charlotte | North Carolina | United States | 28277 |
| 18 | GSK Investigational Site | Gastonia | North Carolina | United States | 28054 |
| 19 | GSK Investigational Site | Hendersonville | North Carolina | United States | 28739 |
| 20 | GSK Investigational Site | Huntersville | North Carolina | United States | 28078 |
| 21 | GSK Investigational Site | Canton | Ohio | United States | 44718 |
| 22 | GSK Investigational Site | Cincinnati | Ohio | United States | 45231 |
| 23 | GSK Investigational Site | Middleburg Heights | Ohio | United States | 44130 |
| 24 | GSK Investigational Site | Medford | Oregon | United States | 97504 |
| 25 | GSK Investigational Site | Bethlehem | Pennsylvania | United States | 18020 |
| 26 | GSK Investigational Site | Greenville | South Carolina | United States | 29615 |
| 27 | GSK Investigational Site | Orangeburg | South Carolina | United States | 29118 |
| 28 | GSK Investigational Site | Rock Hill | South Carolina | United States | 29732 |
| 29 | GSK Investigational Site | Spartanburg | South Carolina | United States | 29303 |
| 30 | GSK Investigational Site | Austin | Texas | United States | 78750 |
| 31 | GSK Investigational Site | Lewisville | Texas | United States | 75067 |
| 32 | GSK Investigational Site | Waco | Texas | United States | 76712 |
| 33 | GSK Investigational Site | Richmond | Virginia | United States | 23225 |
| 34 | GSK Investigational Site | Greenfield | Wisconsin | United States | 53228 |
| 35 | GSK Investigational Site | Florida | Buenos Aires | Argentina | 1602 |
| 36 | GSK Investigational Site | La Plata | Buenos Aires | Argentina | 1900 |
| 37 | GSK Investigational Site | Mar del Plata | Buenos Aires | Argentina | 7600 |
| 38 | GSK Investigational Site | Quilmes | Buenos Aires | Argentina | B1878FNR |
| 39 | GSK Investigational Site | Rosario | Santa Fe | Argentina | S2000DBS |
| 40 | GSK Investigational Site | Rosario | Santa Fe | Argentina | S2000JKR |
| 41 | GSK Investigational Site | Buenos Aires | Argentina | C1424BSF | |
| 42 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Argentina | C1425BEN | |
| 43 | GSK Investigational Site | Ciudad Autónoma de Buenos Aires | Argentina | C1121ABE | |
| 44 | GSK Investigational Site | Ciudad Autónoma de Buenos Aires | Argentina | C1426ABP | |
| 45 | GSK Investigational Site | Mar del Plata | Argentina | B7600FYK | |
| 46 | GSK Investigational Site | Mendoza | Argentina | 5500 | |
| 47 | GSK Investigational Site | Mendoza | Argentina | M5500CCG | |
| 48 | GSK Investigational Site | San Miguel de Tucumán | Argentina | 4000 | |
| 49 | GSK Investigational Site | Salvador | Bahía | Brazil | 41940455 |
| 50 | GSK Investigational Site | Goiânia | Goiás | Brazil | 74110 030 |
| 51 | GSK Investigational Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 |
| 52 | GSK Investigational Site | São Paulo | Brazil | 01323903 | |
| 53 | GSK Investigational Site | São Paulo | Brazil | 04266-010 | |
| 54 | GSK Investigational Site | Concepción | Región Del Biobio | Chile | 4070038 |
| 55 | GSK Investigational Site | Santiago | Región Metro De Santiago | Chile | 7500692 |
| 56 | GSK Investigational Site | Santiago | Región Metro De Santiago | Chile | 7500710 |
| 57 | GSK Investigational Site | Santiago | Región Metro De Santiago | Chile | 7510186 |
| 58 | GSK Investigational Site | Valparaiso | Valparaíso | Chile | 2341131 |
| 59 | GSK Investigational Site | Santiago | Chile | 7500698 | |
| 60 | GSK Investigational Site | Viña del Mar | Chile | 2520594 | |
| 61 | GSK Investigational Site | Ceska Lipa | Czechia | 470 01 | |
| 62 | GSK Investigational Site | Hlucin | Czechia | 748 01 | |
| 63 | GSK Investigational Site | Hradec Kralove | Czechia | 500 02 | |
| 64 | GSK Investigational Site | Kutna Hora | Czechia | 284 01 | |
| 65 | GSK Investigational Site | Lovosice | Czechia | 410 02 | |
| 66 | GSK Investigational Site | Olomouc | Czechia | 772 00 | |
| 67 | GSK Investigational Site | Ostrava - Poruba | Czechia | 70868 | |
| 68 | GSK Investigational Site | Rokycany | Czechia | 337 01 | |
| 69 | GSK Investigational Site | Tabor | Czechia | 390 01 | |
| 70 | GSK Investigational Site | Teplice | Czechia | 415 10 | |
| 71 | GSK Investigational Site | Varnsdorf | Czechia | 407 47 | |
| 72 | GSK Investigational Site | Stuttgart | Baden-Wuerttemberg | Germany | 70378 |
| 73 | GSK Investigational Site | Bamberg | Bayern | Germany | 96049 |
| 74 | GSK Investigational Site | Muenchen | Bayern | Germany | 80339 |
| 75 | GSK Investigational Site | Muenchen | Bayern | Germany | 80539 |
| 76 | GSK Investigational Site | Potsdam | Brandenburg | Germany | 14469 |
| 77 | GSK Investigational Site | Frankfurt | Hessen | Germany | 60389 |
| 78 | GSK Investigational Site | Frankfurt | Hessen | Germany | 60596 |
| 79 | GSK Investigational Site | Marburg | Hessen | Germany | 35037 |
| 80 | GSK Investigational Site | Neu isenburg | Hessen | Germany | 63263 |
| 81 | GSK Investigational Site | Hannover | Niedersachsen | Germany | 30173 |
| 82 | GSK Investigational Site | Peine | Niedersachsen | Germany | 31224 |
| 83 | GSK Investigational Site | Essen | Nordrhein-Westfalen | Germany | 45355 |
| 84 | GSK Investigational Site | Essen | Nordrhein-Westfalen | Germany | 45359 |
| 85 | GSK Investigational Site | Warendorf | Nordrhein-Westfalen | Germany | 48231 |
| 86 | GSK Investigational Site | Witten | Nordrhein-Westfalen | Germany | 58452 |
| 87 | GSK Investigational Site | Koblenz | Rheinland-Pfalz | Germany | 56068 |
| 88 | GSK Investigational Site | Teuchern | Sachsen-Anhalt | Germany | 6682 |
| 89 | GSK Investigational Site | Delitzsch | Sachsen | Germany | 04509 |
| 90 | GSK Investigational Site | Leipzg | Sachsen | Germany | 04109 |
| 91 | GSK Investigational Site | Leipzig | Sachsen | Germany | 04207 |
| 92 | GSK Investigational Site | Leipzig | Sachsen | Germany | 04275 |
| 93 | GSK Investigational Site | Leipzig | Sachsen | Germany | 04357 |
| 94 | GSK Investigational Site | Geesthacht | Schleswig-Holstein | Germany | 21502 |
| 95 | GSK Investigational Site | Luebeck | Schleswig-Holstein | Germany | 23552 |
| 96 | GSK Investigational Site | Schleswig | Schleswig-Holstein | Germany | 24837 |
| 97 | GSK Investigational Site | Schmoelln | Thueringen | Germany | 04626 |
| 98 | GSK Investigational Site | Berlin | Germany | 10119 | |
| 99 | GSK Investigational Site | Berlin | Germany | 10367 | |
| 100 | GSK Investigational Site | Berlin | Germany | 10717 | |
| 101 | GSK Investigational Site | Berlin | Germany | 10787 | |
| 102 | GSK Investigational Site | Berlin | Germany | 10969 | |
| 103 | GSK Investigational Site | Berlin | Germany | 12203 | |
| 104 | GSK Investigational Site | Berlin | Germany | 13156 | |
| 105 | GSK Investigational Site | Hamburg | Germany | 22299 | |
| 106 | GSK Investigational Site | Cheongju-si, Chungcheongbuk-do | Korea, Republic of | 361-763 | |
| 107 | GSK Investigational Site | Incheon | Korea, Republic of | 403-720 | |
| 108 | GSK Investigational Site | Seoul | Korea, Republic of | 110-744 | |
| 109 | GSK Investigational Site | Seoul | Korea, Republic of | 135-710 | |
| 110 | GSK Investigational Site | Seoul | Korea, Republic of | 138-736 | |
| 111 | GSK Investigational Site | Suwon-si, Gyeonggi-do | Korea, Republic of | 16499 | |
| 112 | GSK Investigational Site | Zapopan | Jalisco | Mexico | 45030 |
| 113 | GSK Investigational Site | Zapopan | Jalisco | Mexico | 45070 |
| 114 | GSK Investigational Site | Morelia | Michoacán | Mexico | 58070 |
| 115 | GSK Investigational Site | Monterrey NL | Nuevo León | Mexico | 64718 |
| 116 | GSK Investigational Site | Villahermosa | Tabasco | Mexico | 86035 |
| 117 | GSK Investigational Site | Mexico DF | Mexico | 01710 | |
| 118 | GSK Investigational Site | Almelo | Netherlands | 7609 PP | |
| 119 | GSK Investigational Site | Almere | Netherlands | 1311 RL | |
| 120 | GSK Investigational Site | Almere | Netherlands | 1315 RC | |
| 121 | GSK Investigational Site | Breda | Netherlands | 4818 CK | |
| 122 | GSK Investigational Site | Breda | Netherlands | 4819 EV | |
| 123 | GSK Investigational Site | Eindhoven | Netherlands | 5623 EJ | |
| 124 | GSK Investigational Site | Harderwijk | Netherlands | 3844 DG | |
| 125 | GSK Investigational Site | Hoorn | Netherlands | 1624 NP | |
| 126 | GSK Investigational Site | Kloosterhaar | Netherlands | 7694 AC | |
| 127 | GSK Investigational Site | Nijverdal | Netherlands | 7442 LS | |
| 128 | GSK Investigational Site | Zutphen | Netherlands | 7207 AE | |
| 129 | GSK Investigational Site | Bacau | Romania | 600114 | |
| 130 | GSK Investigational Site | Bacau | Romania | 600252 | |
| 131 | GSK Investigational Site | Brasov | Romania | 500112 | |
| 132 | GSK Investigational Site | Bucharest | Romania | 020125 | |
| 133 | GSK Investigational Site | Bucharest | Romania | 030317 | |
| 134 | GSK Investigational Site | Bucharest | Romania | 050159 | |
| 135 | GSK Investigational Site | Bucuresti | Romania | 022102 | |
| 136 | GSK Investigational Site | Cluj Napoca | Romania | 400371 | |
| 137 | GSK Investigational Site | Codlea | Romania | 505100 | |
| 138 | GSK Investigational Site | Craiova | Romania | 200345 | |
| 139 | GSK Investigational Site | Deva | Romania | 330182 | |
| 140 | GSK Investigational Site | Pitesti | Romania | 110084 | |
| 141 | GSK Investigational Site | Suceava | Romania | 720284 | |
| 142 | GSK Investigational Site | Timisoara | Romania | 300310 | |
| 143 | GSK Investigational Site | Barnaul | Russian Federation | 656 045 | |
| 144 | GSK Investigational Site | Blagoveshchensk | Russian Federation | 675000 | |
| 145 | GSK Investigational Site | Irkutsk | Russian Federation | 664043 | |
| 146 | GSK Investigational Site | Kemerovo | Russian Federation | 650000 | |
| 147 | GSK Investigational Site | Kemerovo | Russian Federation | 650002 | |
| 148 | GSK Investigational Site | Krasnodar | Russian Federation | 350012 | |
| 149 | GSK Investigational Site | Moscow | Russian Federation | 115201 | |
| 150 | GSK Investigational Site | Moscow | Russian Federation | 115478 | |
| 151 | GSK Investigational Site | Moscow | Russian Federation | 123 182 | |
| 152 | GSK Investigational Site | Moscow | Russian Federation | 125315 | |
| 153 | GSK Investigational Site | Omsk | Russian Federation | 644112 | |
| 154 | GSK Investigational Site | Pyatigorsk | Russian Federation | 357538 | |
| 155 | GSK Investigational Site | Saint Petesburg | Russian Federation | 195030 | |
| 156 | GSK Investigational Site | Saint-Petersburg | Russian Federation | 194354 | |
| 157 | GSK Investigational Site | Saint-Petersburg | Russian Federation | 196240 | |
| 158 | GSK Investigational Site | Saratov | Russian Federation | 410028 | |
| 159 | GSK Investigational Site | St'Petersburg | Russian Federation | 197706 | |
| 160 | GSK Investigational Site | St. Petersburg | Russian Federation | 194356 | |
| 161 | GSK Investigational Site | Stavropol | Russian Federation | 355017 | |
| 162 | GSK Investigational Site | Tomsk | Russian Federation | 634009 | |
| 163 | GSK Investigational Site | Tomsk | Russian Federation | 634033 | |
| 164 | GSK Investigational Site | Ufa | Russian Federation | 450071 | |
| 165 | GSK Investigational Site | Ulyanovsk | Russian Federation | 432063 | |
| 166 | GSK Investigational Site | Vladimir | Russian Federation | 600023 | |
| 167 | GSK Investigational Site | Volgodonsk | Russian Federation | 347381 | |
| 168 | GSK Investigational Site | Voronezh | Russian Federation | 394018 | |
| 169 | GSK Investigational Site | Alicante | Spain | 03004 | |
| 170 | GSK Investigational Site | Alzira/Valencia | Spain | 46600 | |
| 171 | GSK Investigational Site | Badalona | Spain | 08916 | |
| 172 | GSK Investigational Site | Barcelona | Spain | 08016 | |
| 173 | GSK Investigational Site | Barcelona | Spain | 08035 | |
| 174 | GSK Investigational Site | Centelles (Barcelona) | Spain | 08540 | |
| 175 | GSK Investigational Site | Madrid | Spain | 28009 | |
| 176 | GSK Investigational Site | Pozuelo De Alarcón/Madrid | Spain | 28223 | |
| 177 | GSK Investigational Site | Santander | Spain | 39008 | |
| 178 | GSK Investigational Site | Santiago de Compostela | Spain | 15706 | |
| 179 | GSK Investigational Site | Valencia | Spain | 46015 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02301975
Other Study ID Numbers:
- 201378
First Posted:
Nov 26, 2014
Last Update Posted:
Aug 6, 2018
Last Verified:
Aug 1, 2018
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Eligible participants at screening and run-in visits entered a 24 Week treatment period and were randomized to receive either Fluticasone furoate/Vilanterol (FF/VI) 100/25 micrograms (mcg) or Fluticasone propionate/salmeterol (FP/S) 250/50mcg or only FP 250mcg followed by a follow-up phase. The total duration for study participation was 30 weeks. |
|---|---|
| Pre-assignment Detail | A total of 3162 adult and adolescent participants with asthma were screened, out of which 516 were screen-failures, 1124 were run-in failures, 1522 participants were randomized, and 1504 subjects received at least one dose of study medication to be included in the Intent-to-Treat (ITT) Population. |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Period Title: Overall Study | |||
| STARTED | 504 | 501 | 499 |
| COMPLETED | 473 | 476 | 477 |
| NOT COMPLETED | 31 | 25 | 22 |
Baseline Characteristics
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Total of all reporting groups |
| Overall Participants | 504 | 501 | 499 | 1504 |
| Age (Mean) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Participants] |
44.4
(16.30)
8.8%
|
43.0
(15.20)
8.6%
|
43.0
(16.58)
8.6%
|
43.5
(16.04)
2.9%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
314
62.3%
|
336
67.1%
|
314
62.9%
|
964
64.1%
|
| Male |
190
37.7%
|
165
32.9%
|
185
37.1%
|
540
35.9%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| American Indian or Alaska native |
0
0%
|
0
0%
|
1
0.2%
|
1
0.1%
|
| Asian - East Asian Heritage |
8
1.6%
|
11
2.2%
|
4
0.8%
|
23
1.5%
|
| Asian- Japanese Heritage |
1
0.2%
|
0
0%
|
0
0%
|
1
0.1%
|
| Asian- South East Asian Heritage |
1
0.2%
|
0
0%
|
1
0.2%
|
2
0.1%
|
| Black/African American Heritage |
12
2.4%
|
14
2.8%
|
17
3.4%
|
43
2.9%
|
| White- Arabic/ North African Heritage |
0
0%
|
1
0.2%
|
2
0.4%
|
3
0.2%
|
| White- White/Caucasian/European Heritage |
415
82.3%
|
407
81.2%
|
410
82.2%
|
1232
81.9%
|
| White- Mixed White Race |
1
0.2%
|
0
0%
|
0
0%
|
1
0.1%
|
| African American/ African and White Heritage |
0
0%
|
5
1%
|
0
0%
|
5
0.3%
|
| American Indian/Alaskan Native and White Heritage |
66
13.1%
|
62
12.4%
|
64
12.8%
|
192
12.8%
|
| Asian - East Asian and White Heritage |
0
0%
|
1
0.2%
|
0
0%
|
1
0.1%
|
Outcome Measures
| Title | Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 487 | 487 | 479 |
| Least Squares Mean (Standard Error) [Liter (L)] |
0.019
(0.0107)
|
0.000
(0.0108)
|
-0.104
(0.0109)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit PM FEV1 for FF/VI and FP/S was more than -100 milliliter (mL) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.019 | |
| Confidence Interval |
(2-Sided) 95% -0.011 to 0.049 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.123 | |
| Confidence Interval |
(2-Sided) 95% 0.093 to 0.153 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.104 | |
| Confidence Interval |
(2-Sided) 95% 0.074 to 0.134 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in PM FEV1 Using Per Protocol (PP) Population |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 425 | 426 | 419 |
| Least Squares Mean (Standard Error) [L] |
0.020
(0.0120)
|
0.014
(0.0120)
|
-0.099
(0.0121)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit for FF/VI and FP/S was more than -100 mL | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.006 | |
| Confidence Interval |
(2-Sided) 95% -0.027 to 0.040 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.120 | |
| Confidence Interval |
(2-Sided) 95% 0.086 to 0.153 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 0.113 | |
| Confidence Interval |
(2-Sided) 95% 0.080 to 0.147 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Percentage of Rescue-free 24-hour Periods |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Weeks 1-24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 500 | 498 | 496 |
| Least Squares Mean (Standard Error) [Percentage of rescue-free 24-hr periods] |
-3.0
(0.62)
|
-4.2
(0.62)
|
-5.7
(0.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 2.7 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 4.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Percentage of Symptom-free 24-hour Periods |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Weeks 1-24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 500 | 498 | 496 |
| Least Squares Mean (Standard Error) [Percentage of symptom-free 24 hour perio] |
-3.5
(0.67)
|
-4.7
(0.67)
|
-6.2
(0.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 3.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 2.7 | |
| Confidence Interval |
(2-Sided) 95% 0.8 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.115 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF) |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Weeks 1-24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 501 | 499 | 497 |
| Least Squares Mean (Standard Error) [Liter per minute (L/min)] |
8.9
(1.48)
|
3.7
(1.49)
|
-12.6
(1.49)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 5.2 | |
| Confidence Interval |
(2-Sided) 95% 1.1 to 9.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 21.5 | |
| Confidence Interval |
(2-Sided) 95% 17.4 to 25.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 16.3 | |
| Confidence Interval |
(2-Sided) 95% 12.2 to 20.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20 |
|---|---|
| Description | 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. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 471 | 467 | 461 |
| Number [Percentage of participants] |
92
18.3%
|
93
18.6%
|
91
18.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 1.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.595 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.15 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 1.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.372 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 2.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in PM PEF |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Weeks 1-24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily |
|---|---|---|---|
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. |
| Measure Participants | 501 | 498 | 496 |
| Least Squares Mean (Standard Error) [L/min] |
5.5
(1.55)
|
0.5
(1.55)
|
-13.7
(1.55)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 5.0 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 9.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 19.2 | |
| Confidence Interval |
(2-Sided) 95% 14.9 to 23.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square mean change difference |
| Estimated Value | 14.2 | |
| Confidence Interval |
(2-Sided) 95% 9.9 to 18.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact one week after completion of study medication (Up to Week 25). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs and SAEs were collected in ITT Population | |||||
| Arm/Group Title | FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily | |||
| Arm/Group Description | Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. | |||
All Cause Mortality |
||||||
| FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/504 (0%) | 0/501 (0%) | 0/499 (0%) | |||
Serious Adverse Events |
||||||
| FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/504 (1.2%) | 4/501 (0.8%) | 5/499 (1%) | |||
| Gastrointestinal disorders | ||||||
| Large intestine perforation | 0/504 (0%) | 1/501 (0.2%) | 0/499 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
| Infections and infestations | ||||||
| Abdominal abscess | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
| Pneumonia | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Ankle fracture | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Foot fracture | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Intervertebral disc protrusion | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Joint instability | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
| Osteoarthritis | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
| Synovial cyst | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Invasive lobular breast carcinoma | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Nervous system disorders | ||||||
| Epilepsy | 0/504 (0%) | 1/501 (0.2%) | 0/499 (0%) | |||
| Psychiatric disorders | ||||||
| Psychotic disorder | 0/504 (0%) | 1/501 (0.2%) | 0/499 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal colic | 1/504 (0.2%) | 0/501 (0%) | 0/499 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Vocal cord leukoplakia | 0/504 (0%) | 1/501 (0.2%) | 0/499 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/504 (0%) | 0/501 (0%) | 1/499 (0.2%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| FF/VI 100/25 mcg Once Daily | FP/S 250/50 mcg Twice Daily | FP 250 mcg Twice Daily | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 126/504 (25%) | 123/501 (24.6%) | 124/499 (24.8%) | |||
| Infections and infestations | ||||||
| Bronchitis | 20/504 (4%) | 10/501 (2%) | 13/499 (2.6%) | |||
| Influenza | 9/504 (1.8%) | 12/501 (2.4%) | 19/499 (3.8%) | |||
| Nasopharyngitis | 61/504 (12.1%) | 67/501 (13.4%) | 57/499 (11.4%) | |||
| Pharyngitis | 15/504 (3%) | 13/501 (2.6%) | 18/499 (3.6%) | |||
| Nervous system disorders | ||||||
| Headache | 41/504 (8.1%) | 37/501 (7.4%) | 40/499 (8%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02301975
Other Study ID Numbers:
- 201378
First Posted:
Nov 26, 2014
Last Update Posted:
Aug 6, 2018
Last Verified:
Aug 1, 2018