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

NCT ID: NCT01316900

Last Updated: 2018-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 846 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-01
• Study Completion Date: 2012-04-24

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 and GW642444 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, GW642444 25mcg, 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

62.5/26 mcg once-daily

GW642444

25 mcg once-daily

Group Type: EXPERIMENTAL

GW642444

Intervention Type: DRUG

25 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

62.5/26 mcg once-daily

Intervention Type: DRUG

GW642444

25 mcg once-daily

Intervention Type: DRUG

tiotropium bromide

18 mcg once-daily

Intervention Type: DRUG

Other Intervention Names

GSK573719/vilanterol trifenatate; GSK573719/vilanterol trifenatate; 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

Birmingham, Alabama, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

DeLand, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Decatur, Georgia, United States

GSK Investigational Site

Saint Charles, Missouri, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Phoenixville, Pennsylvania, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Gaffney, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Rock Hill, South Carolina, United States

GSK Investigational Site

Seneca, South Carolina, United States

GSK Investigational Site

Rapid City, South Dakota, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Newport News, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Clermont-Ferrand, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Nîmes, , France

GSK Investigational Site

Saint-Pierre, , France

GSK Investigational Site

Sinsheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Bamberg, Bavaria, Germany

GSK Investigational Site

Erlangen, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Nuremberg, Bavaria, Germany

GSK Investigational Site

Potsdam, Brandenburg, Germany

GSK Investigational Site

Marburg, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Dortmund, North Rhine-Westphalia, Germany

GSK Investigational Site

Dortmund, North Rhine-Westphalia, 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

Foggia, Apulia, Italy

GSK Investigational Site

Avellino, Campania, Italy

GSK Investigational Site

Pordenone, Friuli Venezia Giulia, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Pietra Ligure (SV), Liguria, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Pavia, Lombardy, Italy

GSK Investigational Site

Tradate (VA), Lombardy, Italy

GSK Investigational Site

Catania, Sicily, Italy

GSK Investigational Site

Pisa, Tuscany, Italy

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Zapopan, Jalisco, Mexico

GSK Investigational Site

Mexico City, , Mexico

GSK Investigational Site

México, , Mexico

GSK Investigational Site

Lima, Lima Province, Peru

GSK Investigational Site

Jesus Maria, Lima region, Peru

GSK Investigational Site

San Borja, Lima region, Peru

GSK Investigational Site

San Isidro, Lima region, Peru

GSK Investigational Site

San Miguel, Lima region, Peru

GSK Investigational Site

Santiago de Surco, Lima region, Peru

GSK Investigational Site

Callao, , Peru

GSK Investigational Site

Lima, , Peru

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Gidle, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Lubliniec, , Poland

GSK Investigational Site

Sopot, , Poland

GSK Investigational Site

Włocławek, , Poland

GSK Investigational Site

Zabrze, , Poland

GSK Investigational Site

Bacau, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Chita, , Russia

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Petrozavodsk, , Russia

GSK Investigational Site

Ryazan, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Voronezh, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Dnipropetrovsk, , Ukraine

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

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Simferopol, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Zaporizhia, , Ukraine

Countries

United States; France; Germany; Italy; Mexico; Peru; Poland; Romania; Russia; Ukraine

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: 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: Dataset Specification

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: Informed Consent 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

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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

113360

Identifier Type: -

Identifier Source: org_study_id