A 24-week Evaluation of GSK573719/Vilanterol (125/25mcg) and Components in COPD

NCT ID: NCT01313637

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-01
• Study Completion Date: 2012-04-19

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

125/25mcg

Group Type: EXPERIMENTAL

GSK573719/GW642444 125/25mcg

Intervention Type: DRUG

125/25mcg

GSK573719

125mcg

Group Type: EXPERIMENTAL

GSK573719 125mcg

Intervention Type: DRUG

125mcg

GW642444

25mcg

Group Type: EXPERIMENTAL

GW642444 25mcg

Intervention Type: DRUG

25mcg

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo only

Intervention Type: DRUG

Placebo

Interventions

GSK573719/GW642444 125/25mcg

125/25mcg

Intervention Type: DRUG

GSK573719 125mcg

125mcg

Intervention Type: DRUG

GW642444 25mcg

25mcg

Intervention Type: DRUG

Placebo only

Placebo

Intervention Type: DRUG

Other Intervention Names

umeclidinium bromide/vilanterol trifenatate; umeclidinium bromide; vilanterol trifenatate; placebo

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 adequately controlled
• Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, 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 GW642444

• 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

Phoenix, Arizona, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Palo Alto, California, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Clearwater, Florida, United States

GSK Investigational Site

DeLand, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Panama City, Florida, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Livonia, Michigan, United States

GSK Investigational Site

Plymouth, Minnesota, United States

GSK Investigational Site

Lincoln, Nebraska, United States

GSK Investigational Site

Cherry Hill, New Jersey, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Easley, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Union, South Carolina, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Aalst, , Belgium

GSK Investigational Site

Edegem, , Belgium

GSK Investigational Site

Genk, , Belgium

GSK Investigational Site

Kortrijk, , Belgium

GSK Investigational Site

Liège, , Belgium

GSK Investigational Site

Aalborg, , Denmark

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Hvidovre, , Denmark

GSK Investigational Site

Næstved, , Denmark

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Roedovre, , Denmark

GSK Investigational Site

Roskilde, , Denmark

GSK Investigational Site

Haapsalu, , Estonia

GSK Investigational Site

Pärnu, , Estonia

GSK Investigational Site

Rakvere, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Montauban, , France

GSK Investigational Site

Nice, , France

GSK Investigational Site

Perpignan, , France

GSK Investigational Site

Reims, , France

GSK Investigational Site

Tarbes, , France

GSK Investigational Site

Toulon, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Tours, , France

GSK Investigational Site

Vieux-Condé, , France

GSK Investigational Site

Dillingen an der Donau, Bavaria, Germany

GSK Investigational Site

Künzing, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Schwabach, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Gelnhausen, Hesse, Germany

GSK Investigational Site

Neu-Isenburg, Hesse, Germany

GSK Investigational Site

Rodgau, Hesse, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzg, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Geesthacht, Schleswig-Holstein, Germany

GSK Investigational Site

Schmölln, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Balassagyarmat, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Deszk, , Hungary

GSK Investigational Site

Farkasgyepű, , Hungary

GSK Investigational Site

Gödöllő, , Hungary

GSK Investigational Site

Gyöngyös, , Hungary

GSK Investigational Site

Nyíregyháza, , Hungary

GSK Investigational Site

Sátoraljaújhely, , Hungary

GSK Investigational Site

Szikszó, , Hungary

GSK Investigational Site

Szombathely, , Hungary

GSK Investigational Site

Törökbálint, , Hungary

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Okayama, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Alkmaar, , Netherlands

GSK Investigational Site

Almelo, , Netherlands

GSK Investigational Site

Almere Stad, , Netherlands

GSK Investigational Site

Beek, , Netherlands

GSK Investigational Site

Ede, , Netherlands

GSK Investigational Site

Eindhoven, , Netherlands

GSK Investigational Site

Enschede, , Netherlands

GSK Investigational Site

Groningen, , Netherlands

GSK Investigational Site

Helmond, , Netherlands

GSK Investigational Site

Hoorn, , Netherlands

GSK Investigational Site

Tubbergen, , Netherlands

GSK Investigational Site

Veldhoven, , Netherlands

GSK Investigational Site

Zutphen, , Netherlands

GSK Investigational Site

Bekkestua, , Norway

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Bodø, , Norway

GSK Investigational Site

Elverum, , Norway

GSK Investigational Site

Kløfta, , Norway

GSK Investigational Site

Skedsmokorset, , Norway

GSK Investigational Site

Stavanger, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Cebu City, , Philippines

GSK Investigational Site

Dasmariñas, Cavite, , Philippines

GSK Investigational Site

Marikina City, , Philippines

GSK Investigational Site

Marilao, Bulacan, , Philippines

GSK Investigational Site

Quezon City, , Philippines

GSK Investigational Site

Bardejov, , Slovakia

GSK Investigational Site

Humenné, , Slovakia

GSK Investigational Site

Poprad, , Slovakia

GSK Investigational Site

Revúca, , Slovakia

GSK Investigational Site

Spišská Nová Ves, , Slovakia

GSK Investigational Site

Vráble, , Slovakia

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Höllviken, , Sweden

GSK Investigational Site

Linköping, , Sweden

GSK Investigational Site

Luleå, , Sweden

GSK Investigational Site

Lund, , Sweden

GSK Investigational Site

Malmo, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Vällingby, , Sweden

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Ivano-Frankivsk, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kiev, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Simferopol, , Ukraine

GSK Investigational Site

Zaporizhia, , Ukraine

Countries

United States; Belgium; Denmark; Estonia; France; Germany; Hungary; Japan; Netherlands; Norway; Philippines; Slovakia; Sweden; Ukraine

References

Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, Kalberg CJ, Church A. Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: a randomized, controlled study. Chest. 2014 May;145(5):981-991. doi: 10.1378/chest.13-1579.

Reference Type: DERIVED

PMID: 24385182 (View on PubMed)

Study Documents

Document Type: Informed Consent Form

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: Individual Participant Data Set

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: Statistical Analysis Plan

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: Clinical Study Report

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

2010-023348-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

113361

Identifier Type: -

Identifier Source: org_study_id