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The purpose of this study is to evaluate the dose-response of 4 doses of umeclidinium bromide in combination with fluticasone furoate compared with fluticasone furoate monotherapy in chronic obstructive pulmonary disease participants with an asthmatic component. The fluticasone furoate/umeclidinium bromide treatments will also be compared to the once-daily inhaled corticosteroid/long-acting beta agonist combination fluticasone furoate/vilanterol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Phase A | Experimental | Eligible subjects will enter a 4-week run-in period and will receive fluticasone propionate/salmeterol. Subjects will then be randomized to receive fluticasone furoate 100 mcg, fluticasone furoate/umeclidinium bromide 100/15.6 mcg, fluticasone furoate/umeclidinium bromide 100/62.5 mcg, fluticasone furoate/umeclidinium bromide 100/125 mcg, fluticasone furoate/umeclidinium bromide 100/250 mcg, or fluticasone furoate/vilanterol 100/25 mcg, respectively for 4 weeks |
|
| Treatment Phase B | Experimental | Subjects completing Treatment Phase A will be randomized to receive either fluticasone furoate/umeclidinium bromide100/250 mcg or fluticasone furoate/umeclidinium bromide/vilanterol 100/250/25 mcg for 1 week. |
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| Treatment Phase C | Experimental | Subjects completing Treatment Phase B will be randomized to receive either the same treatment as in Treatment Phase B, or the same treatment minus the umeclidinium bromide component, for 1 week. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FF | Drug | Fluticasone furoate is available as fluticasone furoate inhalation powder (100 mcg per blister), combination of fluticasone furoate/umeclidinium bromide inhalation powder (fluticasone furoate: 100 mcg per blister, umeclidinium bromide: 15.6, 62.5, 125, or 250 mcg per blister) and combination of fluticasone furoate/vilanterol inhalation powder (fluticasone furoate: 100 mcg per blister, vilanterol: 25 mcg per blister) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinic Trough Forced Expiratory Volume in One Second (FEV1) at the End of Treatment Phase A (Visit 6/Day 29) | FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Change from Baseline in trough FEV1 is defined as the difference in the value obtained at Visit 6 (24 hours post-dose on Visit 5) and the last acceptable/borderline acceptable value obtained prior to randomization (from Visit 2 pre-bronchodilator or Visit 3 pre-dose). Trough FEV1 is defined as the acceptable/borderline acceptable FEV1 value obtained at Visit 6, approximately 24 hours after morning dosing on Visit 5. ITT population is comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. All comparisons for statistical purposes are with the FF 100 µg arm. | Baseline and Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Rescue Medication Use at the End of Treatment Phase A | All participants received the albuterol/salbutamol via MDI as a rescue medication on an as-needed basis. Total daily rescue medication use for a given day is the sum of daytime albuterol/salbutamol use recorded in PM and nighttime albuterol/salbutamol use recorded in AM the next day. The number of puffs of albuterol (salbutamol) MDI used in the last 12 hours for relief of symptoms were recorded morning and evening in the eDiary by the participants. End of Treatment Phase A is the last 7 days of Treatment Phase A. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline rescue medication use, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization |
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Inclusion Criteria:
18 years of age or older
COPD with evidence of an asthmatic component as demonstrated by spirometry, reversibility and current therapy at screening as follows:
Outpatient subjects who are smokers or non-smokers.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Newport Beach | California | 92663 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28947022 | Derived | Lee L, Kerwin E, Collison K, Nelsen L, Wu W, Yang S, Pascoe S. The effect of umeclidinium on lung function and symptoms in patients with fixed airflow obstruction and reversibility to salbutamol: A randomised, 3-phase study. Respir Med. 2017 Oct;131:148-157. doi: 10.1016/j.rmed.2017.08.013. Epub 2017 Aug 14. |
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Participants on inhaled corticosteroid therapy over the previous 12 weeks, including a stable dose during the 4 weeks prior to Visit 0, entered the 4-week run-in period on open-label fluticasone propionate 250 microgram (µg) and salmeterol 50 µg combination. Eligible par. were stratified by smoking status, age and randomized to Treatment Phase A.
Participants (par.) with sufficient signs and symptoms to diagnose as having chronic obstructive pulmonary disease (COPD) and evidence of an asthmatic component as demonstrated by spirometry, reversibility and current therapy at the point of screening were eligible for participation in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | FF 100 µg | Participants received fluticasone furoate (FF) 100 µg once daily in the morning by inhalation using a dry powder inhaler (DPI) for 4 weeks during Treatment Phase A and 1 week during Treatment Phase C. In addition, all participants received supplemental albuterol/salbutamol via metered-dose inhaler (MDI) to be used on an as-needed basis (rescue medication) throughout the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Phase A (4 Weeks) |
|
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| UMEC | Drug | Umeclidinium bromide is available as combination of fluticasone furoate/umeclidinium bromide inhalation powder (fluticasone furoate: 100 mcg per blister, umeclidinium bromide: 15.6, 62.5, 125, or 250 mcg per blister) |
|
| VI | Drug | Vilanterol is available as vilanterol inhalation powder (25 mcg per blister) and combination of fluticasone furoate/vilanterol inhalation powder (fluticasone furoate: 100 mcg per blister, vilanterol: 25 mcg per blister) |
|
| Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6) |
| Mean Change From Baseline in E-RS Total Scores at the End of Treatment Phase A | A daily symptoms score for exacerbations of chronic pulmonary disease tool - Respiratory Symptoms (E-RS) is derived by summing the 11 item-level E-RS scores and has a theoretical range of 0-40, with higher values indicating more severe respiratory symptoms. The Baseline E-RS score is defined as the mean within-subject daily score over the 7 days prior to randomization, with data present for a minimum of 4 of the 7 days. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate Baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline score, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization. All comparisons for statistical purposes are with the FF 100 µg arm. | Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6) |
| Change From Baseline in Daily Morning (AM) PEF (Pre-dose and Pre-rescue Bronchodilator) Measured at Home and Averaged Over the Last 21 Days of Treatment Phase A | Peak expiratory flow (PEF) stability limit was calculated from AM PEF measurements on the 7 days preceding Visit 3 as mean AM PEF from the available 7 days preceding Visit 3 x 80%. PEF stability limit serves as a benchmark of the participants run-in COPD status and used for comparison during the treatment phase to assess subject safety. Change from Baseline over the last 21 days of Treatment Phase A is the difference between the last 21 days of Treatment Phase A and the appropriate Baseline week. The last 21 days of Treatment Phase A include the AM assessments on the date of Visit 6. AM assessments include the date of Visit 6 and the 20 consecutive days preceding the date of Visit. Analysis performed using analysis of covariance with covariates of treatment, age, sex, Baseline AM PEF, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization | Baseline and from Day 8 through Day 29 |
| Change From Trough in Clinic Forced Expiratory Volume (FEV1) at 3 Hours Post-study Treatment at Visit 5/Day 28 | FEV1 was measured in the morning by spirometry. At Visit 5, after trough FEV1 is measured, subject received investigational product. 3 hours post-dose, spirometry was repeated and subject then received 2 puffs of albuterol/salbutamol. After 30 minutes,spirometry was repeated.. Change from Baseline in clinic trough (pre-dose) FEV1 is the difference in the trough value at 3 hours post-dose peak FEV1 and the Baseline value. If the trough value or the Baseline was missing, then change from Baseline was considered as missing. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis done using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-dose trough FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. | Baseline and Day 28 |
| Change in Clinic FEV1 Following 2 Puffs of Albuterol/Salbutamol Given 3 Hours Post-study Treatment Dose at Visit 5/Day 28 | FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Reversibility was measured at Visit 1 and Visit 2 for study eligibility by change in clinic FEV1 within 20 to 60 minutes following 4 inhalations of albuterol/salbutamol and again measured 3 hours after dosing at Visit 5 by change in clinic FEV1 30 minutes following 2 inhalations of albuterol/salbutamol. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (either from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-albuterol/salbutamol FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. | Baseline and Day 28 |
| San Diego |
| California |
| 92117 |
| United States |
| GSK Investigational Site | Upland | California | 91786 | United States |
| GSK Investigational Site | Sunset | Louisiana | 70584 | United States |
| GSK Investigational Site | Minneapolis | Minnesota | 55407 | United States |
| GSK Investigational Site | Charlotte | North Carolina | 28207 | United States |
| GSK Investigational Site | Cincinnati | Ohio | 45231 | United States |
| GSK Investigational Site | Medford | Oregon | 97504 | United States |
| GSK Investigational Site | Gaffney | South Carolina | 29340 | United States |
| GSK Investigational Site | Greenville | South Carolina | 29615 | United States |
| GSK Investigational Site | Rock Hill | South Carolina | 29732 | United States |
| GSK Investigational Site | Spartanburg | South Carolina | 29303 | United States |
| GSK Investigational Site | Union | South Carolina | 29379 | United States |
| GSK Investigational Site | Morgantown | West Virginia | 26505 | United States |
| GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | C1028AAP | Argentina |
| GSK Investigational Site | San Rafael | Mendoza Province | 5600 | Argentina |
| GSK Investigational Site | Rosario | Santa Fe Province | S2000DBS | Argentina |
| GSK Investigational Site | San Miguel de Tucumán | Tucumán Province | 4000 | Argentina |
| GSK Investigational Site | Buenos Aires | C1426ABP | Argentina |
| GSK Investigational Site | Mendoza | 5500 | Argentina |
| GSK Investigational Site | San Miguel de Tucumán | 4000 | Argentina |
| GSK Investigational Site | San Miguel de Tucumán | T4000IFL | Argentina |
| GSK Investigational Site | Frankfurt am Main | Hesse | 60389 | Germany |
| GSK Investigational Site | Frankfurt am Main | Hesse | 60596 | Germany |
| GSK Investigational Site | Neu-Isenburg | Hesse | 63263 | Germany |
| GSK Investigational Site | Hanover | Lower Saxony | 30173 | Germany |
| GSK Investigational Site | Leipzg | Saxony | 04109 | Germany |
| GSK Investigational Site | Teuchern | Saxony-Anhalt | 06682 | Germany |
| GSK Investigational Site | Berlin | 10117 | Germany |
| GSK Investigational Site | Berlin | 10119 | Germany |
| GSK Investigational Site | Hamburg | 20253 | Germany |
| GSK Investigational Site | Bialystok | 15-044 | Poland |
| GSK Investigational Site | Bialystok | 15-430 | Poland |
| GSK Investigational Site | Katowice | 40-645 | Poland |
| GSK Investigational Site | Kielce | 25-734 | Poland |
| GSK Investigational Site | Lodz | 90-242 | Poland |
| GSK Investigational Site | Poznan | 60-214 | Poland |
| GSK Investigational Site | Sopot | 81-741 | Poland |
| GSK Investigational Site | Zgierz | 95-100 | Poland |
| GSK Investigational Site | Żnin | 88-400 | Poland |
| GSK Investigational Site | Bacau | 600252 | Romania |
| GSK Investigational Site | Bucharest | 020125 | Romania |
| GSK Investigational Site | Bucharest | 050159 | Romania |
| GSK Investigational Site | Cluj-Napoca | 400371 | Romania |
| GSK Investigational Site | Comuna Alexandru Cel Bun | 617507 | Romania |
| GSK Investigational Site | Craiova | Romania |
| GSK Investigational Site | Piteşti | 110084 | Romania |
| GSK Investigational Site | Ploieşti | 100184 | Romania |
| GSK Investigational Site | Ploieşti | 100379 | Romania |
| GSK Investigational Site | Timișoara | 300310 | Romania |
| GSK Investigational Site | Blagoveshchensk | 675000 | Russia |
| GSK Investigational Site | Moscow | 105229 | Russia |
| GSK Investigational Site | Moscow | 115446 | Russia |
| GSK Investigational Site | Nizhny Novgorod | 603126 | Russia |
| GSK Investigational Site | Saint Petersburg | 194354 | Russia |
| GSK Investigational Site | Saint Petersburg | 194356 | Russia |
| GSK Investigational Site | Saint Petersburg | 198216 | Russia |
| GSK Investigational Site | Saratov | 410012 | Russia |
| GSK Investigational Site | Sestroretsk | 197706 | Russia |
| GSK Investigational Site | Dnipropetrovsk | 49006 | Ukraine |
| GSK Investigational Site | Dnipropetrovsk | 49051 | Ukraine |
| GSK Investigational Site | Kharkiv | 61002 | Ukraine |
| GSK Investigational Site | Kharkiv | 61124 | Ukraine |
| GSK Investigational Site | Kiev | 03680 | Ukraine |
| GSK Investigational Site | Kyiv | 02091 | Ukraine |
| GSK Investigational Site | Kyiv | 02232 | Ukraine |
| GSK Investigational Site | Kyiv | 3680 | Ukraine |
| FG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| FG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| FG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| FG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A and 1 week during Treatment Phase B and C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| FG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A and 1 week during Treatment Phase C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| FG006 | FF/UMEC/VI 100/250/25 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 250 µg and VI 25 µg once daily in the morning by inhalation using two separate DPIs (FF/UMEC 100/250 & VI 25) for 1 week during Treatment Phase B and C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| COMPLETED |
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| NOT COMPLETED |
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|
| Treatment Phase B (1 Week) |
|
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| Treatment Phase C (1 Week) |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | FF 100 µg | Participants received FF 100 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with UMEC 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with VI 25 µg once daily in the morning by inhalation using a DPI for 4 weeks in Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Clinic Trough Forced Expiratory Volume in One Second (FEV1) at the End of Treatment Phase A (Visit 6/Day 29) | FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Change from Baseline in trough FEV1 is defined as the difference in the value obtained at Visit 6 (24 hours post-dose on Visit 5) and the last acceptable/borderline acceptable value obtained prior to randomization (from Visit 2 pre-bronchodilator or Visit 3 pre-dose). Trough FEV1 is defined as the acceptable/borderline acceptable FEV1 value obtained at Visit 6, approximately 24 hours after morning dosing on Visit 5. ITT population is comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. All comparisons for statistical purposes are with the FF 100 µg arm. | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Mean | Standard Deviation | Liters | Baseline and Day 29 |
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| Secondary | Mean Change From Baseline in Rescue Medication Use at the End of Treatment Phase A | All participants received the albuterol/salbutamol via MDI as a rescue medication on an as-needed basis. Total daily rescue medication use for a given day is the sum of daytime albuterol/salbutamol use recorded in PM and nighttime albuterol/salbutamol use recorded in AM the next day. The number of puffs of albuterol (salbutamol) MDI used in the last 12 hours for relief of symptoms were recorded morning and evening in the eDiary by the participants. End of Treatment Phase A is the last 7 days of Treatment Phase A. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline rescue medication use, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Least Squares Mean | Standard Error | Puffs | Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6) |
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| Secondary | Mean Change From Baseline in E-RS Total Scores at the End of Treatment Phase A | A daily symptoms score for exacerbations of chronic pulmonary disease tool - Respiratory Symptoms (E-RS) is derived by summing the 11 item-level E-RS scores and has a theoretical range of 0-40, with higher values indicating more severe respiratory symptoms. The Baseline E-RS score is defined as the mean within-subject daily score over the 7 days prior to randomization, with data present for a minimum of 4 of the 7 days. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate Baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline score, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization. All comparisons for statistical purposes are with the FF 100 µg arm. | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6) |
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| Secondary | Change From Baseline in Daily Morning (AM) PEF (Pre-dose and Pre-rescue Bronchodilator) Measured at Home and Averaged Over the Last 21 Days of Treatment Phase A | Peak expiratory flow (PEF) stability limit was calculated from AM PEF measurements on the 7 days preceding Visit 3 as mean AM PEF from the available 7 days preceding Visit 3 x 80%. PEF stability limit serves as a benchmark of the participants run-in COPD status and used for comparison during the treatment phase to assess subject safety. Change from Baseline over the last 21 days of Treatment Phase A is the difference between the last 21 days of Treatment Phase A and the appropriate Baseline week. The last 21 days of Treatment Phase A include the AM assessments on the date of Visit 6. AM assessments include the date of Visit 6 and the 20 consecutive days preceding the date of Visit. Analysis performed using analysis of covariance with covariates of treatment, age, sex, Baseline AM PEF, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Least Squares Mean | Standard Error | Liters per minute (L/min) | Baseline and from Day 8 through Day 29 |
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| Secondary | Change From Trough in Clinic Forced Expiratory Volume (FEV1) at 3 Hours Post-study Treatment at Visit 5/Day 28 | FEV1 was measured in the morning by spirometry. At Visit 5, after trough FEV1 is measured, subject received investigational product. 3 hours post-dose, spirometry was repeated and subject then received 2 puffs of albuterol/salbutamol. After 30 minutes,spirometry was repeated.. Change from Baseline in clinic trough (pre-dose) FEV1 is the difference in the trough value at 3 hours post-dose peak FEV1 and the Baseline value. If the trough value or the Baseline was missing, then change from Baseline was considered as missing. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis done using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-dose trough FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Least Squares Mean | Standard Error | Liters (L) | Baseline and Day 28 |
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| Secondary | Change in Clinic FEV1 Following 2 Puffs of Albuterol/Salbutamol Given 3 Hours Post-study Treatment Dose at Visit 5/Day 28 | FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Reversibility was measured at Visit 1 and Visit 2 for study eligibility by change in clinic FEV1 within 20 to 60 minutes following 4 inhalations of albuterol/salbutamol and again measured 3 hours after dosing at Visit 5 by change in clinic FEV1 30 minutes following 2 inhalations of albuterol/salbutamol. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (either from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-albuterol/salbutamol FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. | ITT Population. Only those participants available at the specified time point were analyzed. | Posted | Least Squares Mean | Standard Error | Liters (L) | Baseline and Day 28 |
|
AEs and SAEs were collected from start of the run-in period until follow-up (Visit 8 + 7 days (+/- 2 days). SAEs related to participation or GSK concomitant medication were recorded from time of consent up to and including any follow up contact.
AEs and SAEs were collected for the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Assessed as related to participation might include; study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FF 100 µg | Participants received fluticasone furoate (FF) 100 µg once daily in the morning by inhalation using a dry powder inhaler (DPI) for 4 weeks during Treatment Phase A and 1 week during Treatment Phase C. In addition, all participants received supplemental albuterol/salbutamol via metered-dose inhaler (MDI) to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 111 | 6 | 111 | ||
| EG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 42 | 5 | 42 | ||
| EG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 40 | 4 | 40 | ||
| EG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 46 | 4 | 46 | ||
| EG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A and 1 week during Treatment Phase B and C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 1 | 210 | 5 | 210 | ||
| EG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks during Treatment Phase A and 1 week during Treatment Phase C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 146 | 4 | 146 | ||
| EG006 | FF/UMEC/VI 100/250/25 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 250 µg and VI 25 µg once daily in the morning by inhalation using two separate DPIs (FF/UMEC 100/250 & VI 25) for 1 week during Treatment Phase B and C. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. | 0 | 163 | 0 | 163 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment | One subject had a non-fatal SAE of pneumonia 2 days after withdrawal, which resolved. This subject also had 2 fatal SAEs; TIA and PE, onset 14 and 17 days after last dose, respectively. The investigator considered pneumonia and PE treatment-related. |
|
| Transient ischaemic attack (TIA) | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary embolism (PE) | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001982 | Bronchial Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| Physician Decision |
|
| Adverse Event |
|
| Physician Decision |
|
| Male |
|
| White- Arabic/ North African Heritage |
|
| White- White/Caucasian/European Heritage |
|
| Mixed Race |
|
| Mean Difference (Net) |
| 0.103 |
| 2-Sided |
| 95 |
| 0.014 |
| 0.193 |
| Superiority or Other |
| Final step dose response model | 0.024 | Mean Difference (Net) | 0.103 | 2-Sided | 95 | 0.014 | 0.193 | Superiority or Other |
| Final step dose response model | 0.024 | Mean Difference (Net) | 0.103 | 2-Sided | 95 | 0.014 | 0.193 | Superiority or Other |
| Final dose response model | 0.152 | Mean Difference (Net) | 0.073 | 2-Sided | 95 | -0.027 | 0.172 | Superiority or Other |
| OG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
|
|
|
| OG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
|
|
|
| OG001 | FF/UMEC 100/15.6 µg | Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
|
|
|
| OG001 |
| FF/UMEC 100/15.6 µg |
Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
|
|
|
| FF/UMEC 100/15.6 µg |
Participants received FF 100 µg in combination with umeclidinium bromide (UMEC) 15.6 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG002 | FF/UMEC 100/62.5 µg | Participants received FF 100 µg in combination with UMEC 62.5 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG003 | FF/UMEC 100/125 µg | Participants received FF 100 µg in combination with UMEC 125 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG004 | FF/UMEC 100/250 µg | Participants received FF 100 µg in combination with UMEC 250 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
| OG005 | FF/VI 100/25 µg | Participants received FF 100 µg in combination with vilanterol trifenatate (VI) 25 µg once daily in the morning by inhalation using a DPI for 4 weeks. In addition, all participants received supplemental albuterol/salbutamol via MDI to be used on an as-needed basis (rescue medication) throughout the study. |
|
|
|