A Study to Evaluate Annual Rate of Exacerbations and Safety of 3 Dosage Strengths of Fluticasone Furoate (FF)/GW642444 Inhalation Powder in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01017952
First received: November 19, 2009
Last updated: August 15, 2013
Last verified: August 2013
Results First Received: May 30, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Pulmonary Disease, Chronic Obstructive
Interventions: Drug: FF/GW642444 Inhalation Powder
Drug: GW642444 Inhalation Powder

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At Visit (V) 1, eligible participants (par.) entered a 4-week, open-label Run-in Period (RIP) to establish a stable Baseline. At V 2, eligible par. were randomized to a 52-week, double-blind Treatment Period. 2635 par. were screened, 2092 par. entered the RIP, and 1635 par. were randomized, out of which 1633 par. received >=1 study treatment dose.

Reporting Groups
  Description
FP/SAL 250/50 µg BID Participants (Par.) were instructed to take open label Fluticasone Propionate and Salmeterol (FP/SAL) 250/50 microgram (µg) twice daily (BID) from the ACCUHALER/DISKUS, one inhalation each morning and evening with approximately 12 hours between doses. In addition, all par. were provided supplemental albuterol/salbutamol (metered dose inhaler [MDI] and/or nebules) to be used as needed throughout the study.
VI 25 µg QD Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 50/25 µg QD Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 100/25 µg QD Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 200/25 µg QD Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.

Participant Flow for 2 periods

Period 1:   4-week, Open-label Run-In Period
    FP/SAL 250/50 µg BID     VI 25 µg QD     FF/VI 50/25 µg QD     FF/VI 100/25 µg QD     FF/VI 200/25 µg QD  
STARTED     2092     0     0     0     0  
COMPLETED     1633     0     0     0     0  
NOT COMPLETED     459     0     0     0     0  
Did Not Meet Continuation Criteria                 356                 0                 0                 0                 0  
Adverse Event                 23                 0                 0                 0                 0  
Study Closed/Tterminated                 1                 0                 0                 0                 0  
Lost to Follow-up                 6                 0                 0                 0                 0  
Physician Decision                 10                 0                 0                 0                 0  
Withdrawal by Subject                 63                 0                 0                 0                 0  

Period 2:   52-week, Double-blind Treatment Period
    FP/SAL 250/50 µg BID     VI 25 µg QD     FF/VI 50/25 µg QD     FF/VI 100/25 µg QD     FF/VI 200/25 µg QD  
STARTED     0     409     412     403     409  
Completed the Treatment Period     0     285 [1]   305 [1]   293 [1]   307 [1]
COMPLETED     0     284 [2]   303 [2]   291 [2]   306 [2]
NOT COMPLETED     0     125     109     112     103  
Adverse Event                 0                 25                 32                 35                 30  
Withdrawal by Subject                 0                 30                 22                 25                 25  
Lack of Efficacy                 0                 35                 14                 16                 14  
Protocol Violation                 0                 7                 11                 9                 8  
Met Protocol-Defined Stopping Criteria                 0                 11                 13                 12                 9  
Study Closed/Terminated                 0                 1                 1                 0                 0  
Lost to Follow-up                 0                 6                 8                 6                 10  
Physician Decision                 0                 10                 8                 9                 7  
[1] Par. completed the treatment period if they attended the last treatment visit (Visit 11).
[2] Par. completed the study if they completed the treatment period and safety follow-up phone contact.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
VI 25 µg QD Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 50/25 µg QD Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 100/25 µg QD Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 200/25 µg QD Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the NDPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Total Total of all reporting groups

Baseline Measures
    VI 25 µg QD     FF/VI 50/25 µg QD     FF/VI 100/25 µg QD     FF/VI 200/25 µg QD     Total  
Number of Participants  
[units: participants]
  409     412     403     409     1633  
Age  
[units: Years]
Mean ± Standard Deviation
  63.6  ± 9.29     63.7  ± 9.56     64.0  ± 9.28     63.5  ± 8.84     63.7  ± 9.24  
Gender  
[units: Participants]
         
Female     174     181     181     191     727  
Male     235     231     222     218     906  
Race/Ethnicity, Customized  
[units: participants]
         
White     360     359     353     359     1431  
African American/ African Heritage     9     14     7     9     39  
Asian     4     3     5     3     15  
African American/African Heritage & White     0     1     1     0     2  
American Indian or Alaska Native & White     20     19     21     20     80  
Asian & White     0     0     0     1     1  
Native Hawaiian or other Pacific Islander     0     0     0     1     1  
American Indian or Alaska Native     16     16     16     16     64  



  Outcome Measures
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1.  Primary:   Annual Rate of Moderate and Severe COPD Exacerbations Expressed as Least Square Mean   [ Time Frame: From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal ]

2.  Secondary:   Time to First Occurrence of Moderate or Severe COPD Exacerbation   [ Time Frame: From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal ]

3.  Secondary:   Annual Rate of Exacerbations Requiring Systemic/Oral Corticosteroids Expressed as Least Square Mean   [ Time Frame: From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal ]

4.  Secondary:   Change From Baseline in Trough FEV1 at Week 52 (Visit 11)   [ Time Frame: Baseline to Visit 11 (Week 52)/Early Withdrawal ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Serious adverse events (SAEs) and non-serious AEs will be collected from Baseline to the end of the treatment period (up to 52 weeks).
Additional Description SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.

Frequency Threshold
Threshold above which other adverse events are reported   3%  

Reporting Groups
  Description
VI 25 µg QD Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 50/25 µg QD Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 100/25 µg QD Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
FF/VI 200/25 µg QD Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.

Other Adverse Events
    VI 25 µg QD     FF/VI 50/25 µg QD     FF/VI 100/25 µg QD     FF/VI 200/25 µg QD  
Total, other (not including serious) adverse events          
# participants affected / at risk     211/409     229/412     239/403     249/409  
Gastrointestinal disorders          
Diarrhoea † 1        
# participants affected / at risk     4/409 (0.98%)     10/412 (2.43%)     14/403 (3.47%)     15/409 (3.67%)  
General disorders          
Oedema peripheral † 1        
# participants affected / at risk     16/409 (3.91%)     12/412 (2.91%)     12/403 (2.98%)     8/409 (1.96%)  
Infections and infestations          
Nasopharyngitis † 1        
# participants affected / at risk     58/409 (14.18%)     54/412 (13.11%)     68/403 (16.87%)     82/409 (20.05%)  
Oral candidiasis † 1        
# participants affected / at risk     29/409 (7.09%)     39/412 (9.47%)     39/403 (9.68%)     40/409 (9.78%)  
Upper respiratory tract infection † 1        
# participants affected / at risk     31/409 (7.58%)     37/412 (8.98%)     39/403 (9.68%)     36/409 (8.80%)  
Sinusitis † 1        
# participants affected / at risk     19/409 (4.65%)     26/412 (6.31%)     20/403 (4.96%)     27/409 (6.60%)  
Bronchitis † 1        
# participants affected / at risk     20/409 (4.89%)     25/412 (6.07%)     16/403 (3.97%)     23/409 (5.62%)  
Influenza † 1        
# participants affected / at risk     6/409 (1.47%)     18/412 (4.37%)     14/403 (3.47%)     18/409 (4.40%)  
Pharyngitis † 1        
# participants affected / at risk     12/409 (2.93%)     10/412 (2.43%)     10/403 (2.48%)     13/409 (3.18%)  
Rhinitis † 1        
# participants affected / at risk     12/409 (2.93%)     14/412 (3.40%)     5/403 (1.24%)     10/409 (2.44%)  
Pneumonia † 1        
# participants affected / at risk     6/409 (1.47%)     8/412 (1.94%)     14/403 (3.47%)     11/409 (2.69%)  
Lower respiratory tract infection † 1        
# participants affected / at risk     13/409 (3.18%)     7/412 (1.70%)     12/403 (2.98%)     5/409 (1.22%)  
Oropharyngeal candidiasis † 1        
# participants affected / at risk     3/409 (0.73%)     15/412 (3.64%)     11/403 (2.73%)     5/409 (1.22%)  
Musculoskeletal and connective tissue disorders          
Back pain † 1        
# participants affected / at risk     23/409 (5.62%)     19/412 (4.61%)     30/403 (7.44%)     17/409 (4.16%)  
Arthralgia † 1        
# participants affected / at risk     17/409 (4.16%)     6/412 (1.46%)     20/403 (4.96%)     13/409 (3.18%)  
Nervous system disorders          
Headache † 1        
# participants affected / at risk     30/409 (7.33%)     34/412 (8.25%)     32/403 (7.94%)     33/409 (8.07%)  
Respiratory, thoracic and mediastinal disorders          
Oropharyngeal pain † 1        
# participants affected / at risk     18/409 (4.40%)     23/412 (5.58%)     17/403 (4.22%)     26/409 (6.36%)  
Cough † 1        
# participants affected / at risk     20/409 (4.89%)     14/412 (3.40%)     15/403 (3.72%)     22/409 (5.38%)  
Dyspnoea † 1        
# participants affected / at risk     16/409 (3.91%)     12/412 (2.91%)     13/403 (3.23%)     10/409 (2.44%)  
Vascular disorders          
Hypertension † 1        
# participants affected / at risk     16/409 (3.91%)     12/412 (2.91%)     10/403 (2.48%)     15/409 (3.67%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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