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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Multicenter Trial Comparing the Efficacy and Safety of GSK573719/GW642444 With GW642444 and With Tiotropium Over 24 Weeks in Subjects With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01316900
• Other study ID #: 113360
• Status: Completed
• Phase: Phase 3
• First received: March 15, 2011
• Last updated: January 18, 2018
• Start date: March 1, 2011
• Est. completion date: April 24, 2012

Study information

• Verified date: January 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 846
• Est. completion date: April 24, 2012
• Est. primary completion date: April 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GSK573719/GW642444 125/25
125/25 mcg once-daily
• GSK573719/GW642444 62.5/25
62.5/26 mcg once-daily
• GW642444
25 mcg once-daily
• tiotropium bromide
18 mcg once-daily

Locations

Country	Name	City	State
France	GSK Investigational Site	Clermont Ferrand cedex 1
France	GSK Investigational Site	Nantes cedex 1
France	GSK Investigational Site	Nîmes cedex 09
France	GSK Investigational Site	Saint Pierre Cedex
Germany	GSK Investigational Site	Bamberg	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Marburg	Hessen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Nuernberg	Bayern
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Sinsheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Italy	GSK Investigational Site	Avellino	Campania
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Foggia	Puglia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Pietra Ligure (SV)	Liguria
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Pordenone	Friuli-Venezia-Giulia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Tradate (VA)	Lombardia
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Zapopan	Jalisco
Peru	GSK Investigational Site	Callao
Peru	GSK Investigational Site	Jesus Maria	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima 27	Lima
Peru	GSK Investigational Site	San Borja	Lima
Peru	GSK Investigational Site	San Isidro	Lima
Peru	GSK Investigational Site	San Miguel	Lima
Peru	GSK Investigational Site	Santiago de Surco	Lima
Poland	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	Wloclawek
Poland	GSK Investigational Site	Zabrze
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Chita
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Petrozavodsk
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
Ukraine	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
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Phoenixville	Pennsylvania
United States	GSK Investigational Site	Rapid City	South Dakota
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline (BL) in the Mean Shortness of Breath With Daily Activities (SOBDA) Score for Week 24	The newly developed SOBDA questionnaire assesses dyspnea or shortness of breath (SOB) with daily activities. The SOBDA questionnaire is made up of 13 items completed by the participant (par.) each evening prior to bedtime, when the par. is instructed to reflect on the current day's activities. The daily score is computed as the mean of the scores on the 13 items (>=7 items must have non-missing responses for this to be calculated). The par. is assigned a weekly mean SOBDA score ranging from 1 to 4 (greater scores indicate more severe breathlessness with daily activities) based on the mean of 7 days of data (>=4 of 7 days must be completed for a weekly mean to be calculated). Change from BL is the mean weekly SOBDA score minus BL. Analysis was performed using MMRM with covariates of treatment, BL (mean score in the week prior to treatment), smoking status, center group, week, week by BL and week by treatment interactions. This MMRM analysis only included Weeks 4, 8, 12, and 24.	Baseline and Week 24
Primary	Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84, 112, 168, and 169. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions. ITT=Intent-to-Treat; par.=participants. .	Baseline and Day 169
Secondary	Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 168	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1, 84, and Day 168 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 15 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours. Change from BL at a particular visit was calculated as WM at that visit minus BL. Analysis was performed using a repeated measures model with covariates of treatment, BL (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by BL and day by treatment interactions.	Baseline and Day 168

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