A 24-week Evaluation of GSK573719/Vilanterol (62.5/25mcg) and Components in COPD

NCT ID: NCT01313650

Last Updated: 2018-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1538 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-01
• Study Completion Date: 2012-04-05

Brief Summary

This is a phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of GSK573719/GW642444 Inhalation Powder, GSK573719 Inhalation Powder, GW642444 Inhalation Powder and Placebo when administered once-daily via a Novel Dry Powder Inhaler over a 24-week treatment period in subjects with COPD. Subjects who meet eligibility criteria at Screening (Visit 1) will complete a 7 to14 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 27 weeks. A subset of subjects at selected sites will also perform 24-hour serial spirometry and Holter monitoring during the study and provide serial blood samples for pharmacokinetic analysis. Sparse pharmacokinetic sampling for population pharmacokinetic analyses will be obtained from non-subset subjects. The primary measure of efficacy is clinic visit trough (pre-bronchodilator and pre-dose) FEV1 on Treatment Day 169. Safety will be assessed by adverse events, 12-lead ECGs, vital signs, clinical laboratory tests, and 24 hour Holter monitoring (subset only).

Detailed Description

This is a 24-week, phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

Eligible subjects will be randomized to GSK573719/GW642444 125/25mcg, GSK573719 125mcg, GW642444 25mcg, and placebo treatment groups in a 3:3:3:2 ratio such that of the planned 1463 total number of randomized subjects approximately 399 subjects will be randomized to each active treatment group and 266 subjects will be randomized to placebo. All treatments will be administered once-daily in the morning by inhalation using a Novel Dry Powder Inhaler (Novel DPI).

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 14 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 27 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/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, 4, 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 evening throughout the run-in and treatment periods. Subjects will use the eDiary to record 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. Disease specific health status will be evaluated using the subject-completed St. George's Respiratory Questionnaire (SGRQ). The SGRQ will be completed at Visits 2, 4, 6, and 8. Administration of the SGRQ and BDI/TDI should be done prior to spirometry testing.

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. Blood samples for population pharmacokinetic analyses will be obtained.

At selected study sites, a subset of approximately 198 subjects will perform 24-hour serial spirometry during the study for evaluation of lung function over the dosing period. In conjunction with the serial spirometry, this subset of subjects will also perform 24 hour Holter monitoring and provide blood samples for PK analysis.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

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

Study Groups

GSK573719/GW642444

62.5/25mcg

Group Type: EXPERIMENTAL

62.5/25mcg

Intervention Type: DRUG

GSK573719/GW64244

GSK573719

62.5mcg

Group Type: EXPERIMENTAL

62.5mcg

Intervention Type: DRUG

GSK573719

GW642444

25mcg

Group Type: EXPERIMENTAL

25mcg

Intervention Type: DRUG

GW642444

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

62.5/25mcg

GSK573719/GW64244

Intervention Type: DRUG

62.5mcg

GSK573719

Intervention Type: DRUG

25mcg

GW642444

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of COPD
• 10 pack-year or greater history of cigarette smoking
• Post-bronchodilator FEV1/FVC of <0.7
• Predicted FEV1 of 70% of normal or less
• Modified Medical Research Council (mMRC) dyspnea score of 2 or greater

Exclusion Criteria

• Women who are pregnant, lactating, or planning to become pregnant
• Respiratory disorders other than COPD, including a current diagnosis of asthma
• Clinically significant non-respiratory diseases or abnormalities that are not adequate controlled
• Significant allergy or hypersensitivity to anticholinergics, beta-agonist, or the excipients of magnesium stereate or lactose used in the inhaler delivery device
• Hospitalization for COPD or pneumonia within 12 weeks prior to screening
• Lung volume reduction surgery within 12 weeks prior to screening
• Abnormal and clinically significant ECG findings at screening
• Clinically significant laboratory findings at screening
• Use of systemic corticosteroids, antibiotics for respiratory tract infections, strong cytochrome P450 3A4 inhibitors, high dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, ipratropium, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit
• Use of long-term oxygen therapy (12 hours or greater per day)
• Regular use of nebulized treatment with short-acting bronchodilators
• Participation in the acute phase of a pulmonary rehabilitation program
• A know or suspected history of alcohol or drug abuse
• Affiliation with the investigational site
• Previous use of GSK573719 or GW642444 alone or in combination, including the combination of fluticasone furoate and GW64244

• 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

Tucson, Arizona, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Ormond Beach, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Lawrenceville, Georgia, United States

GSK Investigational Site

Coeur d'Alene, Idaho, United States

GSK Investigational Site

Lafayette, Indiana, United States

GSK Investigational Site

Olathe, Kansas, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Madisonville, Kentucky, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Sunset, Louisiana, United States

GSK Investigational Site

Cadillac, Michigan, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Larchmont, New York, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Dayton, Ohio, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Beaver, Pennsylvania, United States

GSK Investigational Site

Erie, Pennsylvania, United States

GSK Investigational Site

Phoenixville, Pennsylvania, United States

GSK Investigational Site

Gaffney, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Pelzer, South Carolina, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Rapid City, South Dakota, United States

GSK Investigational Site

Johnson City, Tennessee, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Kingwood, Texas, United States

GSK Investigational Site

Abingdon, Virginia, United States

GSK Investigational Site

Newport News, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Dimitrovgrad, , Bulgaria

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Rousse, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Troyan Municipality, , Bulgaria

GSK Investigational Site

Varna, , Bulgaria

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Burlington, Ontario, Canada

GSK Investigational Site

Grimsby, Ontario, Canada

GSK Investigational Site

Sarnia, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Pointe-Claire, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Saint-Charles-Borromée, Quebec, Canada

GSK Investigational Site

Trois-Rivières, Quebec, Canada

GSK Investigational Site

Rancagua, Reg Del Libert Bern Ohiggins, Chile

GSK Investigational Site

Valparaíso, Región de Valparaíso, Chile

GSK Investigational Site

Puente Alto - 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

Talcahuano, , Chile

GSK Investigational Site

Viña del Mar, , Chile

GSK Investigational Site

Český Krumlov, , Czechia

GSK Investigational Site

Kralupy nad Vltavou, , Czechia

GSK Investigational Site

Kyjov, , Czechia

GSK Investigational Site

Lovosice, , Czechia

GSK Investigational Site

Nový Jičín, , Czechia

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Pilsen, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Praha 5 - Radotin, , Czechia

GSK Investigational Site

Rokycany, , Czechia

GSK Investigational Site

Teplice, , Czechia

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Haidari / Athens, , Greece

GSK Investigational Site

Heraklion, Crete, , Greece

GSK Investigational Site

Larissa, , Greece

GSK Investigational Site

Serres, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Fukushima, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kumamoto, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Saitama, , Japan

GSK Investigational Site

Shimane, , Japan

GSK Investigational Site

Shimane, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Zapopan, Jalisco, Mexico

GSK Investigational Site

Monterrey, Nuevo León, Mexico

GSK Investigational Site

Puebla, Pue, Puebla, Mexico

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Gidle, , Poland

GSK Investigational Site

Grudziądz, , Poland

GSK Investigational Site

Iława, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Szczecin, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Łomża, , Poland

GSK Investigational Site

Arkhangelsk, , Russia

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Blagoveshchensk, , Russia

GSK Investigational Site

Krasnoyarsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Nizhny Novgorod, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Perm, , Russia

GSK Investigational Site

Pyatigorsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Ufa, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Benoni, Gauteng, South Africa

GSK Investigational Site

Meyerspark, Gauteng, South Africa

GSK Investigational Site

Bloemfontein, , South Africa

GSK Investigational Site

Durban, , South Africa

GSK Investigational Site

Gatesville, , South Africa

GSK Investigational Site

Mowbray, , South Africa

GSK Investigational Site

Newtown, , South Africa

GSK Investigational Site

Somerset West, , South Africa

GSK Investigational Site

Tygerberg, , South Africa

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Badalona / Barcelona, , Spain

GSK Investigational Site

Barakaldo (Vizcaya), , Spain

GSK Investigational Site

Cáceres, , Spain

GSK Investigational Site

Centelles, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Palma de Mallorca, , Spain

GSK Investigational Site

Pamplona, , Spain

GSK Investigational Site

Pozuelo de Alarcón/Madrid, , Spain

GSK Investigational Site

Salt (gerona), , Spain

GSK Investigational Site

Sant Boi de Llobregat - Barcelona, , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Chiang Mai, , Thailand

GSK Investigational Site

Khon Kaen, , Thailand

GSK Investigational Site

Nonthaburi, , Thailand

GSK Investigational Site

Songkhla, , Thailand

Countries

United States; Bulgaria; Canada; Chile; Czechia; Greece; Japan; Mexico; Poland; Russia; South Africa; Spain; Thailand

References

Donohue JF, Maleki-Yazdi MR, Kilbride S, Mehta R, Kalberg C, Church A. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med. 2013 Oct;107(10):1538-46. doi: 10.1016/j.rmed.2013.06.001. Epub 2013 Jul 2.

Reference Type: DERIVED

PMID: 23830094 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

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

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: Study Protocol

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

View Document

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

Related Links

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Other Identifiers

2010-023349-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

113373

Identifier Type: -

Identifier Source: org_study_id