Trial Outcomes & Findings for GW815SF For Chronic Obstructive Pulmonary Disease (Chronic Bronchitis, Emphysema) (NCT NCT00269087)

Last Updated: 2019-02-01

Results Overview

AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

122 participants

Primary outcome timeframe

Up to Week 56

Results posted on

2019-02-01

Participant Flow

A study was conducted at 20 centers in Japan from 28 December 2004 to 25 October 2006.

The study period consisted of 2-week run-in period (could be extended up to 4 weeks). Total 174 participants entered into the study, of which 127 participants were screened and entered into run-in phase. Five participants withdrew from the study during run-in phase and total 122 participants received study medication.

Participant milestones

Participant milestones
Measure	GW815SF 50/500 µg Participants received one inhalation of GW815SF 50/500 micrograms (µg) (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Overall Study STARTED	122
Overall Study COMPLETED	88
Overall Study NOT COMPLETED	34

Reasons for withdrawal

Reasons for withdrawal
Measure	GW815SF 50/500 µg Participants received one inhalation of GW815SF 50/500 micrograms (µg) (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Overall Study Adverse Event	20
Overall Study Withdrawal by Subject	1
Overall Study Exacerbation of COPD	13

Baseline Characteristics

GW815SF For Chronic Obstructive Pulmonary Disease (Chronic Bronchitis, Emphysema)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Age, Continuous	70.2 Years STANDARD_DEVIATION 6.34 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	122 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 56

Population: Safety Population included all participants who had received an investigational product even for once.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Any Adverse Events (AEs) and Serious AEs (SAEs) Any AEs	120 Participants
Number of Participants With Any Adverse Events (AEs) and Serious AEs (SAEs) Any SAEs	27 Participants

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameters: Red blood cells (RBC), Hemoglobin (Hb), Hematocrit, Platelet count (PC), White blood cells (WBC), Basophils, Eosinophils, Neutrophils, Lymphocytes and Monocytes were presented as the outliers from the normal range as \> upper limit and \< lower limit. Only number of participants with hematology values outside normal range were presented.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 52/Withdrawal, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Basophils, Baseline, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Basophils, Week 4, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Basophils, Week 12, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Basophils, Week 36, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Baseline, < lower limit	30 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 4, < lower limit	36 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 12, < lower limit	36 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 24, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 24, < lower limit	21 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 36, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 36, < lower limit	22 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 52/Withdrawal, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters RBC, Week 52/Withdrawal, < lower limit	33 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Baseline, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Baseline, < lower limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Week 4, < lower limit	20 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Week 12, < lower limit	20 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Week 24, < lower limit	13 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Week 36, < lower limit	14 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hb, Week 52/Withdrawal, <lower limit	27 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Baseline, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Baseline, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 4, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 4, < lower limit	13 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 12, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 12, < lower limit	13 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 24, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 24, < lower limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit, Week 36, < lower limit	12 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Hematocrit,Week 52/Withdrawal,< lower limit	17 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Baseline, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Baseline, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 4, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 4, < lower limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 12, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 12, < lower limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 24, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 24, < lower limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 36, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 36, < lower limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 52/Withdrawal, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters PC, Week 52/Withdrawal, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Baseline, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Baseline, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 4, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 4, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 12, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 24, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 24, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 36, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters WBC, Week 36, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Basophils, Week 52/Withdrawal, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils, Baseline, > upper limit	17 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils, Week 4, > upper limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils, Week 12, > upper limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils, Week 24, > upper limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils, Week 36, > upper limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Eosinophils,Week 52/Withdrawal,> upper limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Baseline, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Baseline, < lower limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 4, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 4, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 12, > upper limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 24, > upper limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 36, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils, Week 36, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils,Week 52/Withdrawal,>upper limit	11 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Neutrophils,Week 52/Withdrawal,< lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Baseline, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Baseline, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Week 4, < lower limit	16 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Week 12, < lower limit	17 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Week 24, < lower limit	25 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes, Week 36, < lower limit	16 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Lymphocytes,Week 52/Withdrawal,< lower limit	19 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, Baseline, > upper limit	31 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, Week 4, > upper limit	47 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, Week 12, > upper limit	37 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, Week 24, > upper limit	25 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, Week 36, > upper limit	28 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Hematology Parameters Monocytes, wEEK 52/Withdrawal,> upper limit	14 Participants

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters: Total bilirubin (TB), Alkaline phosphatase (Al-P), Alanine aminotransferase (ALT), Asparate aminotransferase (AST), Gamma-glutamyl transpeptidase (GTP), Lactate dehydrogenase (LDH), Total cholesterol (TC), Glucose, Creatinine, Blood urea nitrogen (BUN), Uric acid (UA), Sodium (Na), Potassium (K), Chloride (Cl) and Calcium (Ca) were presented as the outliers from the normal range as \> upper limit and \< lower limit. Only number of participants with clinical chemistry values outside normal range were presented.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 4, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 12, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 12, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 24, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Baseline, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 4, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 12, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 12, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 24, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 36, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 36, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TB, Week 52/ withdrawal, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Baseline, > upper limit	18 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 4, > upper limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 12, > upper limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 24, > upper limit	18 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 24, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 36, > upper limit	12 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AL-P, Week 52/ withdrawal, > upper limit	13 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Baseline, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Week 4, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Week 12, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Week 24, > upper limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Week 36, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters ALT, Week 52/ withdrawal, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Baseline, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Week 4, > upper limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Week 12, > upper limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Week 24, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Week 36, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters AST, Week 52/ withdrawal, > upper limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Baseline, > upper limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Baseline, < lower limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 4, > upper limit	17 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 4, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 12, > upper limit	14 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 12, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 24, > upper limit	12 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 24, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 36, > upper limit	12 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP, Week 36, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP,Week 52/withdrawal, > upper limit	15 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Gamma GTP,Week 52/withdrawal, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Baseline, > upper limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 4, > upper limit	11 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 12, > upper limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 24, > upper limit	14 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 36, > upper limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 36, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters LDH, Week 52/ withdrawal, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Baseline, > upper limit	17 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Baseline, < lower limit	13 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 4, > upper limit	19 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 4, < lower limit	16 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 12, > upper limit	21 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 12, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 24, > upper limit	20 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 24, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 36, > upper limit	22 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 36, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 52/ withdrawal, > upper limit	27 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters TC, Week 52/ withdrawal, < lower limit	10 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Baseline, > upper limit	40 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Baseline, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 4, > upper limit	42 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 4, < lower limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 12, > upper limit	42 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 12, < lower limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 24, > upper limit	31 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 24, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 36, > upper limit	34 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 36, < lower limit	5 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 52/ withdrawal, > upper limit	45 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Glucose, Week 52/ withdrawal, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Baseline, > upper limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Baseline, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 4, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 4, < lower limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 12, > upper limit	8 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 12, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 24, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 24, < lower limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 36, > upper limit	9 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine, Week 36, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine,Week 52/withdrawal, >upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Creatinine,Week 52/withdrawal, <lower limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Baseline, > upper limit	31 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Baseline, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 4, > upper limit	16 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 4, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 12, > upper limit	23 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 12, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 24, > upper limit	18 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 36, > upper limit	21 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 52/ withdrawal, > upper limit	22 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters BUN, Week 52/ withdrawal, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Baseline, > upper limit	35 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Week 4, > upper limit	31 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Week 12, > upper limit	29 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Week 24, > upper limit	19 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Week 36, > upper limit	21 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters UA, Week 52/ withdrawal, > upper limit	32 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Baseline, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 4, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 4, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 12, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 24, > upper limit	6 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 36, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Na, Week 52/ withdrawal, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Baseline, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Baseline, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 4, > upper limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 12, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 12, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 24, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 24, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 36, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 52/ withdrawal, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters K, Week 52/ withdrawal, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Baseline, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Baseline, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 4, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 24, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 36, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 52/ withdrawal, > upper limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Cl, Week 52/ withdrawal, < lower limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Baseline, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Baseline, < lower limit	2 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 4, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 4, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 12, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 12, < lower limit	1 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 24, > upper limit	7 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 36, > upper limit	4 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 52/ withdrawal, > upper limit	3 Participants
Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry Parameters Ca, Week 52/ withdrawal, < lower limit	1 Participants

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population

Urinalysis parameters: Urine protein, Glucose and Urobilinogen were presented as shift from Baseline. Only number of participants with urinalysis values more than Baseline values were presented. The plus sign increases with a higher level of glucose and proteins in the urine: 1+: slightly positive, 2+: positive, 3+: high positive and 4+: strongly positive.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 4, 1+ to 3+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 4, 3+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 12, 1+ to 2+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 12, 1+ to 3+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 12, 2+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 12, 3+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 24, 1+ to 2+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 24, 1+ to 3+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 24, 1+ to 2+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 24, 1+ to 4+	2 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 24, 2+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 36, 1+ to 2+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 36, 1+ to 3+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 36, 1+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 36, 2+ to 4+	2 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 36, 3+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Urine protein, Week 52/withdrawal, 1+ to 3+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 52/withdrawal, 1+ to 2+	2 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 52/withdrawal, 1+ to 4+	1 Participants
Number of Participants With Abnormal (Shift From Baseline) Urinalysis Parameters Glucose, Week 52/withdrawal, 2+ to 4+	1 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24 and 52

Population: Safety Population. Only those participants available at the specified time points were analyzed.

On each assessment day at Week 24 and 52, adrenal cortical function tests were performed between 8:00-10:00 in the morning. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance. Blood samples were taken from participants at rest before undergoing spirometry. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Level of Plasma Cortisol 1 Week 24	0.86 Micrograms per decilitre (µg/dL) Standard Deviation 2.945
Mean Change From Baseline in Level of Plasma Cortisol 1 Week 52/Withdrawal	-0.62 Micrograms per decilitre (µg/dL) Standard Deviation 3.118

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

On each assessment day at Week 24, 52 and follow up, adrenal cortical function tests were performed between 8:00-10:00 in the morning. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance. Blood samples were taken from participants at rest before undergoing spirometry.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Level of Plasma Cortisol 2 Baseline	9.41 µg/dL Geometric Coefficient of Variation 26.69
Mean Level of Plasma Cortisol 2 Week 24	10.08 µg/dL Geometric Coefficient of Variation 34.19
Mean Level of Plasma Cortisol 2 Week 52/Withdrawal	8.49 µg/dL Geometric Coefficient of Variation 38.63

SECONDARY outcome

Timeframe: Baseline and up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Systolic and diastolic BP was measured in sitting position. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 4	0.5 Millimeter of mercury (mmHg) Standard Deviation 14.22
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 8	-0.1 Millimeter of mercury (mmHg) Standard Deviation 14.74
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 12	0.6 Millimeter of mercury (mmHg) Standard Deviation 15.85
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 16	0.7 Millimeter of mercury (mmHg) Standard Deviation 15.98
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 20	-0.8 Millimeter of mercury (mmHg) Standard Deviation 17.08
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 24	0.2 Millimeter of mercury (mmHg) Standard Deviation 16.50
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 28	-0.4 Millimeter of mercury (mmHg) Standard Deviation 17.10
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 32	-1.8 Millimeter of mercury (mmHg) Standard Deviation 17.74
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 36	1.1 Millimeter of mercury (mmHg) Standard Deviation 17.67
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 40	0.4 Millimeter of mercury (mmHg) Standard Deviation 17.09
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 44	-3.1 Millimeter of mercury (mmHg) Standard Deviation 17.48
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 48	-4.1 Millimeter of mercury (mmHg) Standard Deviation 16.23
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 52 / withdrawal	0.3 Millimeter of mercury (mmHg) Standard Deviation 18.12
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 4	-0.7 Millimeter of mercury (mmHg) Standard Deviation 9.22
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 8	-1.2 Millimeter of mercury (mmHg) Standard Deviation 9.22
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 12	0.3 Millimeter of mercury (mmHg) Standard Deviation 9.72
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 16	0.3 Millimeter of mercury (mmHg) Standard Deviation 10.07
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 20	-1.4 Millimeter of mercury (mmHg) Standard Deviation 9.91
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 24	0.6 Millimeter of mercury (mmHg) Standard Deviation 9.88
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 28	-0.6 Millimeter of mercury (mmHg) Standard Deviation 10.00
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 32	-1.4 Millimeter of mercury (mmHg) Standard Deviation 11.35
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 36	0.0 Millimeter of mercury (mmHg) Standard Deviation 10.16
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 40	-1.3 Millimeter of mercury (mmHg) Standard Deviation 10.66
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 44	-2.1 Millimeter of mercury (mmHg) Standard Deviation 11.01
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 48	-2.9 Millimeter of mercury (mmHg) Standard Deviation 9.44
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 52 / withdrawal	-0.1 Millimeter of mercury (mmHg) Standard Deviation 10.42

SECONDARY outcome

Timeframe: Baseline and up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Pulse rate was measured in sitting position. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Pulse Rate Week 4	-1.5 beats per min Standard Deviation 11.19
Mean Change From Baseline in Pulse Rate Week 8	-1.6 beats per min Standard Deviation 10.12
Mean Change From Baseline in Pulse Rate Week 12	-0.4 beats per min Standard Deviation 10.40
Mean Change From Baseline in Pulse Rate Week 16	1.0 beats per min Standard Deviation 10.03
Mean Change From Baseline in Pulse Rate Week 20	1.1 beats per min Standard Deviation 11.19
Mean Change From Baseline in Pulse Rate Week 24	1.4 beats per min Standard Deviation 11.74
Mean Change From Baseline in Pulse Rate Week 28	1.2 beats per min Standard Deviation 10.23
Mean Change From Baseline in Pulse Rate Week 32	0.4 beats per min Standard Deviation 10.69
Mean Change From Baseline in Pulse Rate Week 36	0.9 beats per min Standard Deviation 9.76
Mean Change From Baseline in Pulse Rate Week 40	0.7 beats per min Standard Deviation 10.94
Mean Change From Baseline in Pulse Rate Week 44	0.4 beats per min Standard Deviation 11.00
Mean Change From Baseline in Pulse Rate Week 48	-0.2 beats per min Standard Deviation 10.66
Mean Change From Baseline in Pulse Rate Week 52 / withdrawal	0.8 beats per min Standard Deviation 11.18

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Oropharyngeal examination was performed in participants with suspected oral infection (candidiasis).

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal Oropharyngeal Examination Findings Week -2	1 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 0	1 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 4	3 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 8	7 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 12	7 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 16	9 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 20	9 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 24	9 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 28	6 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 32	7 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 36	7 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 40	7 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 44	4 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week 48	4 Participants
Number of Participants With Abnormal Oropharyngeal Examination Findings Week52 / withdrawal	8 Participants

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population.

On each assessment day at Week 24, 52 and follow up 12-lead ECG was performed. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal (Clinically Significant) Electrocardiogram (ECG) Findings Baseline	2 Participants
Number of Participants With Abnormal (Clinically Significant) Electrocardiogram (ECG) Findings Week 24	3 Participants
Number of Participants With Abnormal (Clinically Significant) Electrocardiogram (ECG) Findings Withdrawal	4 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 56

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

On each assessment day at Week 52 and follow up, lumber (L1-L4) BMD was determined with a BMD meter by the dual energy X-ray absorption (DEXA) method. Baseline value was the measurement taken during run-in period. Change from Baseline was any value post Baseline minus value at Baseline.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=24 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Bone Mineral Density (BMD)	-0.014 Grams per centimeter square Standard Deviation 0.0618

SECONDARY outcome

Timeframe: Baseline and up to Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Body weight was measured during run-in period, at Week 24 and 52.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Weight Withdrawal	-0.51 Kilograms Standard Deviation 2.188
Mean Change From Baseline in Weight Week 24	0.17 Kilograms Standard Deviation 1.785

SECONDARY outcome

Timeframe: Up to Week 56

Population: Safety Population

On each assessment day at Week 24, 52 and follow up, ophthalmological examinations (vision, cornea, lens, intraocular pressure, fundus oculi) were performed to determine the presence or absence of glaucoma and cataract.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Cataract, Baseline	3 Participants
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Cataract, Week 24	2 Participants
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Cataract, Withdrawal	3 Participants
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Glaucoma, Baseline	4 Participants
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Glucoma, Week 24	4 Participants
Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations Findings Glucoma, Withdrawal	4 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: Full analysis set (FAS) Population included all enrolled Population excluding those who had not received investigational product at all and those who had no available data regarding efficacy after starting treatment with investigational product. Only those participants available at the specified time points were analyzed.

PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as Baseline. Change from Baseline was any post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 4	0.315 Liters per second Standard Deviation 0.6108
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 8	0.446 Liters per second Standard Deviation 0.6561
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 12	0.394 Liters per second Standard Deviation 0.6607
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 16	0.357 Liters per second Standard Deviation 0.6991
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 20	0.309 Liters per second Standard Deviation 0.6281
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 24	0.328 Liters per second Standard Deviation 0.6912
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 28	0.334 Liters per second Standard Deviation 0.7185
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 32	0.269 Liters per second Standard Deviation 0.7712
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 36	0.350 Liters per second Standard Deviation 0.7354
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 40	0.277 Liters per second Standard Deviation 0.7510
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 44	0.307 Liters per second Standard Deviation 0.7610
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 48	0.314 Liters per second Standard Deviation 0.7600
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 52	0.296 Liters per second Standard Deviation 0.7666
Mean Change From Baseline in Peak Expiratory Flow (PEF) Week 52/ withdrawal	0.229 Liters per second Standard Deviation 0.7942

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: FAS Population. Only those participants available at the specified time points were analyzed.

FVC was the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as Baseline. Change from Baseline was any post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 4	0.128 Liters Standard Deviation 0.3048
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 8	0.156 Liters Standard Deviation 0.3411
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 12	0.142 Liters Standard Deviation 0.3772
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 16	0.140 Liters Standard Deviation 0.3199
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 20	0.106 Liters Standard Deviation 0.3318
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 24	0.127 Liters Standard Deviation 0.3247
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 28	0.149 Liters Standard Deviation 0.4115
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 32	0.142 Liters Standard Deviation 0.3587
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 36	0.147 Liters Standard Deviation 0.3447
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 40	0.148 Liters Standard Deviation 0.3803
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 44	0.156 Liters Standard Deviation 0.3699
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 48	0.147 Liters Standard Deviation 0.3713
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 52	0.170 Liters Standard Deviation 0.3841
Mean Change From Baseline in Forced Vital Capacity (FVC) Week 52/ withdrawal	0.096 Liters Standard Deviation 0.4400

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: FAS Population. Only those participants available at the specified time points were analyzed.

V25 and V 50 were measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as baseline. Change from Baseline was any post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Baseline	0.018 Liter per second Standard Deviation 0.0595
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 8	0.021 Liter per second Standard Deviation 0.0685
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 12	0.015 Liter per second Standard Deviation 0.0611
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 16	0.016 Liter per second Standard Deviation 0.0713
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 20	0.012 Liter per second Standard Deviation 0.0693
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 24	0.017 Liter per second Standard Deviation 0.0649
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 28	0.012 Liter per second Standard Deviation 0.0753
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 32	0.009 Liter per second Standard Deviation 0.0628
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 36	0.018 Liter per second Standard Deviation 0.0689
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 40	0.022 Liter per second Standard Deviation 0.0715
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 44	0.015 Liter per second Standard Deviation 0.0681
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 48	0.010 Liter per second Standard Deviation 0.0735
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 52	0.017 Liter per second Standard Deviation 0.0839
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V25, Week 52/ withdrawal	0.012 Liter per second Standard Deviation 0.0819
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 4	0.044 Liter per second Standard Deviation 0.1708
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 8	0.076 Liter per second Standard Deviation 0.1665
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 12	0.054 Liter per second Standard Deviation 0.1797
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 16	0.060 Liter per second Standard Deviation 0.1555
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 20	0.040 Liter per second Standard Deviation 0.1839
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 24	0.047 Liter per second Standard Deviation 0.1891
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 28	0.049 Liter per second Standard Deviation 0.1799
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 32	0.053 Liter per second Standard Deviation 0.1866
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 36	0.046 Liter per second Standard Deviation 0.1980
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 40	0.053 Liter per second Standard Deviation 0.1953
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 44	0.046 Liter per second Standard Deviation 0.1879
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 48	0.038 Liter per second Standard Deviation 0.1807
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 52	0.059 Liter per second Standard Deviation 0.2050
Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital Capacity V50, Week 52/ withdrawal	0.045 Liter per second Standard Deviation 0.2024

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: FAS Population.

Rescue medication (salbutamol sulfate aerosol provided as an investigational product) was issued to a participant and, when necessary, a spacer at the start of the run-in period. At each time of entry in the Chronic Obstructive Pulmonary Disease (COPD) diary, a participant recorded the number of occasions of rescue medication inhaled in the previous 24 hours in the COPD diary. Baseline was mean value of the consecutive 7 days just before Visit 2. Change from Baseline was any post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Change From Baseline in Percent of Days Without Use of Rescue Medication	15.6 Percentage of days Standard Deviation 33.96

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: FAS Population

A participant recorded scores on the scale of 0 to 4 for breathlessness and nighttime awakenings, where 0 indicated no symptoms and 4 indicated severe symptoms; on the scale of 0 to 3 for cough and sputum production, where 0 indicated no symptoms and 3 indicated severe symptoms, in the 24 hours prior to each entry in the COPD diary. Baseline was mean value of the consecutive 7 days just before Visit2. Change from Baseline was any post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Change From Baseline in Symptom Score With Respect to Breathlessness, Cough, Sputum and Nighttime Awakenings Breathlessness, treatment period	-0.2 Scores on a scale Standard Deviation 0.57
Change From Baseline in Symptom Score With Respect to Breathlessness, Cough, Sputum and Nighttime Awakenings Cough, treatment period	0.0 Scores on a scale Standard Deviation 0.51
Change From Baseline in Symptom Score With Respect to Breathlessness, Cough, Sputum and Nighttime Awakenings Sputum, treatment period	0.0 Scores on a scale Standard Deviation 0.50
Change From Baseline in Symptom Score With Respect to Breathlessness, Cough, Sputum and Nighttime Awakenings Nighttime awakenings, treatment period	-0.1 Scores on a scale Standard Deviation 0.53

SECONDARY outcome

Timeframe: Up to Week 56

Population: FAS Population.

An exacerbation was defined as worsening of the participant's symptoms of cough, sputum production and breathlessness requiring a change in medication. When a moderate or severe COPD exacerbation was observed, details (date of onset, outcome, date of resolution/death, severity, medications provided for treatment, whether the COPD exacerbation required hospitalization, whether the COPD exacerbation required participant withdrawal from the study) were recorded.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=122 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Frequency of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	0.456 Number of exacerbations Standard Deviation 1.3560

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

Population: All participants evaluable for pharmacokinetic parameters were included in PK Population. Only those participants with data available at the indicated time points were analyzed.

For analysis of pharmacokinetic (PK) parameters for FP, blood samples were taken just before dosing (within one hour prior to dosing), 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=12 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Observed Maximum Plasma Concentration (Cmax) of Fluticasone Propionate (FP)	124.63 Picograms per milliliter (pg/mL) Standard Deviation 38.597

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

Population: All evaluable subjects. Only those participants with data available at the indicated time points were analyzed.

For analysis of PK parameters for salmeterol, blood samples were taken just before dosing (within one hour prior to dosing), 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=12 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Cmax of Salmeterol	66.04 pg/mL Standard Deviation 24.955

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

Population: All evaluable subjects. Only those participants with data available at the indicated time points were analyzed.

For analysis of PK parameters for FP, blood samples were taken just before dosing (within one hour prior to dosing), 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=12 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Median Time of Observed Maximum Plasma Concentration (Tmax) of FP	0.875 hours Interval 0.5 to 4.0

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

Population: All evaluable subjects. Only those participants with data available at the indicated time points were analyzed.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=12 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Median Tmax of Salmeterol	0.250 hour Interval 0.08 to 2.0

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

Population: All evaluable subjects. Only those participants with data available at the indicated time points were analyzed.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=12 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Area Under the Plasma Concentration-time Curve Over a Dosing Interval [AUC(0-tau)] of FP	903.48 Hours*picogram per milliliter Standard Deviation 303.721

SECONDARY outcome

Timeframe: Within one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

Population: All evaluable subjects. Only those participants with data available at the indicated time points were analyzed.

Outcome measures

Outcome measures
Measure	GW815SF 50/500 µg n=10 Participants Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Mean Area Under the Plasma Concentration-time Curve From Zero up to the Last Quantifiable Plasma Concentration [AUC (0-t)] of Salmeterol	158.16 Hours*picogram per milliliter Standard Deviation 81.987

Adverse Events

GW815SF 50/500 µg

Serious events: 27 serious events

Other events: 105 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	GW815SF 50/500 µg n=122 participants at risk Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Infections and infestations Pneumonia	8.2% 10/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Atypical mycobacterial infection	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Influenza	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Oesophageal candidiasis	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Respiratory tract infection	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive airways disease exacerbated	7.4% 9/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.6% 2/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Gastrointestinal disorders Colonic polyp	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Gastrointestinal disorders Gastric ulcer	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Gastrointestinal disorders Inguinal hernia	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Gastrointestinal disorders Reflux oesophagitis	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Ear and labyrinth disorders Vertigo positional	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
General disorders Malaise	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Injury, poisoning and procedural complications Contusion	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Injury, poisoning and procedural complications Wound	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Metabolism and nutrition disorders Diabetes mellitus	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Vascular disorders Atherosclerosis obliterans	0.82% 1/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.

Other adverse events

Other adverse events
Measure	GW815SF 50/500 µg n=122 participants at risk Participants received one inhalation of GW815SF 50/500 µg (50 µg salmeterol and 500 µg fluticasone propionate) twice daily for 52 weeks. Participants also received Salbutamol sulfate aerosol as a rescue medication on an as-needed basis.
Infections and infestations Nasopharyngitis	48.4% 59/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Oral candidiasis	18.0% 22/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Bronchitis acute	9.8% 12/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Pneumonia	9.0% 11/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Bronchitis	7.4% 9/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Infections and infestations Pharyngitis	6.6% 8/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Dysphonia	23.8% 29/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive airways disease exacerbated	13.9% 17/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	13.1% 16/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Back pain	6.6% 8/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Muscle spasms	6.6% 8/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.
Gastrointestinal disorders Constipation	7.4% 9/122 • All on-treatment AEs and SAEs were assessed up to Week 56 On-treatment AEs and SAEs were reported for Safety Population.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER