24-week Trial Comparing GSK573719/GW642444 With GSK573719 and With Tiotropium in Chronic Obstructive Pulmonary Disease

NCT ID: NCT01316913

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 872 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-04-30

Brief Summary

This is a Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study to evaluate the efficacy and safety of two doses of GSK573719/GW642444 Inhalation Powder, GSK573719 Inhalation Powder via a Novel Dry Powder Inhaler and tiotropium via HandiHaler when administered once-daily over a 24-week treatment period in subjects with chronic obstructive pulmonary disease (COPD). Subjects who meet eligibility criteria at Screening (Visit 1) will complete a 7 to10 day run-in period followed by a randomization visit (Visit 2) then a 24-week treatment period. There will be a total of 9 clinic study visits. A follow-up phone contact for adverse event assessment will be conducted approximately one week after the last study visit (Visit 9 or Early Withdrawal). The total duration of subject participation in the study will be approximately 26 weeks. The primary measure of efficacy is clinic visit trough (pre-bronchodilator and pre-dose) forced expiratory volume in one second (FEV1) on Treatment Day 169. Safety will be assessed by adverse events, 12-lead ECGs, vital signs, and clinical laboratory tests.

Detailed Description

This is a 24-week, Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study. Eligible subjects will be randomized to GSK573719/GW642444 125/25mcg, GSK573719/GW642444 62.5/25mcg, GSK573719 125mcg, or tiotropium treatment groups in a 1:1:1:1 ratio. Treatments will be administered once-daily in the morning by inhalation using a Novel Dry Powder Inhaler (Novel DPI) and HandiHaler. There will be a total of 9 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 7 to 10 day run-in period followed by a 24-week treatment period. Clinic visits will be at Screening, Randomization (Day 1), Day 2, after 4, 8, 12, 16, and 24-weeks of treatment, and 1 day after the Week 24 Visit (also referred as Treatment Day 169). A follow-up contact for adverse assessment will be conducted by telephone approximately 7 days after Visit 9 or the Early Withdrawal Visit. The total duration of subject participation, including follow-up will be approximately 26 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and study treatment periods. At screening, pre-bronchodilator spirometry testing will be followed by post-albuterol/salbutamol spirometry testing. Post-albuterol/salbutamol FEV1 and FEV1/forced vital capacity (FVC) values will be used to determine subject eligibility. To further characterize bronchodilator responsiveness, post-ipratropium testing will be conducted following completion of post-albuterol/salbutamol spirometry. Spirometry will be conducted at each post-randomization clinic visit. Six hour post-dose serial spirometry will be conducted at Visits 2, 6, and 8. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits 3 to 9. All subjects will be provided with an electronic diary (eDiary) for completion daily in the morning and the evening throughout the run-in and treatment periods. Subjects will use the eDiary to record peak expiratory flow (PEF) each morning, dyspnea scores using the Shortness of Breath with Daily Activities instrument (SOBDA), daily use of supplemental albuterol/salbutamol as either puffs/day from a metered-dose inhaler (MDI) and/or nebules used per day, and any healthcare contacts related to COPD. Additional assessments of dyspnea will be obtained using the Baseline and Transition Dyspnea Index (BDI/TDI) which is an interviewer based instrument. At Visit 2, the severity of dyspnea at baseline will be assessed using the BDI. At subsequent visits (Visits 4, 6, and 8) change from baseline will be assessed using the TDI. General health status will be evaluated using the subject-completed EQ-5D questionnaire at Visits 2, 4, 6, and 8. Disease specific health status will be evaluated using the subject-completed St. George's Respiratory Questionnaire (SGRQ) at Visits 2, 4, 6, and 8, and the subject-completed COPD Assessment Test (CAT) at Visits 2, 6, and 8. The occurrence of adverse events will be evaluated throughout the study beginning at Visit 2. SAEs will be collected over the same time period as for AEs. However, any SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication, will be recorded from the time a subject consents to participate in the study up to and including any follow up contact. Additional safety assessments of vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and chemistry) will be obtained at selected clinic visits.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GSK573719/GW642444 125/25

125/25 mcg once-daily

Group Type: EXPERIMENTAL

GSK573719/GW642444 125/25

Intervention Type: DRUG

125/25 mcg once-daily

GSK573719/GW642444 62.5/25

62.5/25 mcg once-daily

Group Type: EXPERIMENTAL

GSK573719/GW642444 62.5/25

Intervention Type: DRUG

62.5/25 mcg once-daily

GSK573719

125 mcg once-daily

Group Type: EXPERIMENTAL

GSK573719

Intervention Type: DRUG

125 mcg once-daily

tiotropium bromide

18 mcg once-daily

Group Type: ACTIVE_COMPARATOR

tiotropium bromide

Intervention Type: DRUG

18 mcg once-daily

Interventions

GSK573719/GW642444 125/25

125/25 mcg once-daily

Intervention Type: DRUG

GSK573719/GW642444 62.5/25

62.5/25 mcg once-daily

Intervention Type: DRUG

GSK573719

125 mcg once-daily

Intervention Type: DRUG

tiotropium bromide

18 mcg once-daily

Intervention Type: DRUG

Other Intervention Names

GSK573719/vilanterol trifenatate; GSK573719/vilanterol trifenatate

Eligibility Criteria

Inclusion Criteria

• outpatient
• signed and dated written informed consent
• 40 years of age or older
• male and female subjects
• COPD diagnosis
• at least 10 pack-year smoking history
• post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and post-albuterol/salbutamol FEV1 of less than or equal to 70% predicted normal values
• score of greater than or equal to 2 on the Modified Medical Resarch Council Dyspnea Scale (mMRC)

Exclusion Criteria

• women who are pregnant or lactating or are planning on becoming pregnant during the study
• current diagnosis of asthma
• other respiratory disorders other than COPD
• other diseases/abnormalities that are uncontrolled including cancer not in remission for at least 5 years
• chest x-ray or CT scan with clinically significant abnormalities not believed to be due to COPD
• hypersensitivity to anticholinergics, beta-agonists, lactose/milk protein or magnesium stearate or medical conditions associated with inhaled anticholinergics
• hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1
• lung volume reduction surgery within 12 months prior to Visit 1
• abnormal and clinically significant ECG at Visit 1
• significantly abnormal finding from laboratory tests at Visit 1
• unable to withhold albuterol/salbutamol at least 4 hours prior to spirometry at each visit
• use of depot corticosteroids within 12 weeks of Visit 1
• use of oral or parenteral corticosteroids, antibiotics for lower respiratory tract infection, or cytochrome P450 3A4 inhibitors, within 6 weeks of Visit 1
• use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if LABA/ICS therapy is discontinued withing 30 days of Visit 1
• use of ICS at a dose of >1000mcg/day of fluticasone propionate or equivalent within 30 days of Visit 1
• initiation or discontinuation of ICS within 30 days of Visit 1
• use of tiotropium or roflumilast within 14 days of Visit 1
• use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or inhaled long-acting beta-agonists within 48 hours of Visit 1
• short-acting oral beta-agonists within 12 hours of Visit 1
• use of LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy within 48 hours of Visit 1 for the LABA component
• use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1
• use of inhaled short-acting beta-agonists, inhaled short-acting anticholinergics, or inhaled short-acting anticholinergic/short-acting beta-agonist combination products within 4 hours of Visit 1
• use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
• long-term oxygen therapy prescribed for >12 hours per day
• regular use of nebulized short-acting bronchodilators
• participation in acute phase of pulmonary rehabilitation program
• known or suspected history of alcohol or drug abse within 2 years prior to Visit 1
• anyone affiliated with the investigator site (e.g., investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member)
• previous exposure to GSK573719, GSK573719/GW642444 combination, GW642444 (vilanterol), or fluticasone furoate/GW642444 combination

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Jasper, Alabama, United States

GSK Investigational Site

Mobile, Alabama, United States

GSK Investigational Site

Huntington Beach, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Clearwater, Florida, United States

GSK Investigational Site

Ormond Beach, Florida, United States

GSK Investigational Site

Lawrenceville, Georgia, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Madisonville, Kentucky, United States

GSK Investigational Site

Lafayette, Louisiana, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Elizabeth City, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Beaver, Pennsylvania, United States

GSK Investigational Site

Easley, South Carolina, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Morgantown, West Virginia, United States

GSK Investigational Site

Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Mendoza, Mendoza Province, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Concord, New South Wales, Australia

GSK Investigational Site

Cairns, Queensland, Australia

GSK Investigational Site

Carina Heights, Queensland, Australia

GSK Investigational Site

Kippa-Ring, Queensland, Australia

GSK Investigational Site

Adelaide, South Australia, Australia

GSK Investigational Site

Daw Park, South Australia, Australia

GSK Investigational Site

Frankston, Victoria, Australia

GSK Investigational Site

Parkville, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Bay Roberts, Newfoundland and Labrador, Canada

GSK Investigational Site

Truro, Nova Scotia, Canada

GSK Investigational Site

Greater Sudbury, Ontario, Canada

GSK Investigational Site

Mississauga, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Gatineau, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

St-Romulad, Quebec, Canada

GSK Investigational Site

Port Montt, Los Lagos Region, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Talca, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Schwetzingen, Baden-Wurttemberg, Germany

GSK Investigational Site

Aschaffenburg, Bavaria, Germany

GSK Investigational Site

Oranienburg, Brandenburg, Germany

GSK Investigational Site

Rüdersdorf, Brandenburg, Germany

GSK Investigational Site

Schwedt, Brandenburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Kassel, Hesse, Germany

GSK Investigational Site

Wolfenbüttel, Lower Saxony, Germany

GSK Investigational Site

Düren, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Koblenz, Rhineland-Palatinate, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Durango, Durango, Mexico

GSK Investigational Site

Zapopan, Jalisco, Mexico

GSK Investigational Site

Monterrey, Nuevo León, Mexico

GSK Investigational Site

México, , Mexico

GSK Investigational Site

Constanța, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Târgovişte, , Romania

GSK Investigational Site

Bloemfontein, , South Africa

GSK Investigational Site

Boksburg North, , South Africa

GSK Investigational Site

Die Wilgers, , South Africa

GSK Investigational Site

Durban, , South Africa

GSK Investigational Site

Gatesville, , South Africa

GSK Investigational Site

Groenkloof, , South Africa

GSK Investigational Site

Pretoria, , South Africa

GSK Investigational Site

Thabazimbi, , South Africa

GSK Investigational Site

Bucheon-si, , South Korea

GSK Investigational Site

Cheongju, Chungcheongbuk-do, , South Korea

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Kangwon-do, , South Korea

GSK Investigational Site

Seongnam-si, Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Suwon, Kyonggi-do, , South Korea

Countries

United States; Argentina; Australia; Canada; Chile; Germany; Mexico; Romania; South Africa; South Korea

References

Maleki-Yazdi MR, Singh D, Anzueto A, Tombs L, Fahy WA, Naya I. Assessing Short-term Deterioration in Maintenance-naive Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials. Adv Ther. 2017 Jan;33(12):2188-2199. doi: 10.1007/s12325-016-0430-6. Epub 2016 Oct 28.

Reference Type: DERIVED

PMID: 27796912 (View on PubMed)

Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, Tabberer M, Harris S, Church A. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014 Jun;2(6):472-86. doi: 10.1016/S2213-2600(14)70065-7. Epub 2014 May 14.

Reference Type: DERIVED

PMID: 24835833 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

113374

Identifier Type: -

Identifier Source: org_study_id