Trial Outcomes & Findings for ADOAIR250 Anti-inflammatory Effects in Japanese Subjects With Chronic Obstructive Pulmonary Disease (NCT NCT01607398)

NCT ID: NCT01607398

Last Updated: 2014-05-26

Results Overview

Induced sputum samples were collected at Baseline and at Week 12. The neutrophil count in induced sputum was measured with the use of a cytological specimen of inflammatory cells in the induced sputum. Change from Baseline in neutrophil count was calculated as the Week 12 value minus the Baseline value (percentage of neutrophil of total cells in induced sputum at Week 12 minus the Baseline value).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 56 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2014-05-26

Participant Flow

Japanese participants with Chronic Obstructive Pulmonary Disease (COPD) were enrolled in this study.

At Visit 1, participants meeting the inclusion criteria and not meeting any of the exclusion criteria entered a 4-week Run-in Period. At the end of the Run-in Period (Visit 2), eligible participants were randomized to a 12-week Treatment Period.

Participant milestones

Measure	Placebo Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Overall Study STARTED	28	28
Overall Study COMPLETED	26	26
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Placebo Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Overall Study Adverse Event	0	2
Overall Study Severe COPD	2	0

Baseline Characteristics

ADOAIR250 Anti-inflammatory Effects in Japanese Subjects With Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	Total n=52 Participants Total of all reporting groups
Age, Continuous	62.2 Years STANDARD_DEVIATION 8.06 • n=5 Participants	64.7 Years STANDARD_DEVIATION 9.31 • n=7 Participants	63.4 Years STANDARD_DEVIATION 8.72 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Japanese Heritage	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population: all participants who had an evaluable sputum sample at Baseline and at the endpoint of interest, were randomized to study treatment and received at least one dose of study medication, and had no major protocol violations. Only those participants available at the specified time points were analyzed.

Induced sputum samples were collected at Baseline and at Week 12. The neutrophil count in induced sputum was measured with the use of a cytological specimen of inflammatory cells in the induced sputum. Change from Baseline in neutrophil count was calculated as the Week 12 value minus the Baseline value (percentage of neutrophil of total cells in induced sputum at Week 12 minus the Baseline value).

Outcome measures

Measure	Placebo n=21 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=24 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in Neutrophil Count in Induced Sputum at Week 12	1.35 ratio (%) Interval -15.5 to 6.3	-6.00 ratio (%) Interval -30.5 to 6.9

SECONDARY outcome

Timeframe: Baseline and Week 12

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

Induced sputum samples were collected at Baseline and at Week 12. All inflammatory cells in induced sputum were counted with the use of a cytological specimen of cells in the induced sputum. Change from Baseline in all inflammatory cell count was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=25 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=24 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in All Inflammatory Cell Count in Induced Sputum at Week 12	-0.0080 Cells per millimeters cubed (cells/mm^3) Interval -0.356 to 0.14	-0.0280 Cells per millimeters cubed (cells/mm^3) Interval -0.317 to 0.2255

SECONDARY outcome

Timeframe: Baseline and Week 12

INF-gamma-positive cells and perforin-positive cells were not detected in samples collected in this study due to the conditions of the samples and/or antibodies. No re-assays were performed, "no result"/"no data" was entered into the case report forms, and no statistical analysis or data summarization was performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

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

Induced sputum samples were collected at Baseline and at Week 12. The levels of IL-8 in the supernatant of an induced sputum sample were measured at the same time using the multiplex assay system. Change from Baseline in IL-8 levels was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=25 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=25 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in Interleukin (IL)-8 Levels in Sputum Supernatant at Week 12	-5.0 Picograms per milliliter (pg/mL) Interval -177.0 to 267.2	-30.0 Picograms per milliliter (pg/mL) Interval -1930.0 to 850.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Data cannot be reported because hsCRP was under the lower limit of detection in all samples.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

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

Induced sputum samples were collected at Baseline and at Week 12. The levels of MPO and SP-D in the supernatant of an induced sputum sample were measured at the same time using the multiplex assay system. Change from Baseline in MPO and SP-D levels was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=25 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=25 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in Myeloperoxidase (MPO) and Pulmonary Surfactant Protein (SP)-D Levels in Sputum Supernatant at Week 12 MPO	1.80 ng/mL Interval -227.3 to 49.8	-23.90 ng/mL Interval -157.2 to 33.1
Change From Baseline in Myeloperoxidase (MPO) and Pulmonary Surfactant Protein (SP)-D Levels in Sputum Supernatant at Week 12 SP-D	0.00 ng/mL Interval -17.3 to 7.8	0.00 ng/mL Interval -19.1 to 42.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Serum samples were collected at Baseline and at Week 12. The levels of IL-6 and IL-8 in serum samples were measured at the same time using the multiplex assay system. Change from Baseline in IL-6 and IL-8 levels was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in IL-6 and IL-8 Levels in Serum at Week 12 IL-6	0.30 pg/mL Interval -0.1 to 1.4	0.35 pg/mL Interval -0.4 to 1.0
Change From Baseline in IL-6 and IL-8 Levels in Serum at Week 12 IL-8	-1.80 pg/mL Interval -5.5 to 6.6	-0.20 pg/mL Interval -2.2 to 2.6

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Serum samples were collected at Baseline and at Week 12. The levels of hsCRP, SP-D, and CC16 in serum samples were measured at the same time using the multiplex assay system. Change from Baseline in hsCRP, SP-D, and CC16 was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in hsCRP, SP-D, and Clara Cell Protein 16 (CC 16) Levels in Serum at Week 12 hsCRP	107.0 ng/mL Interval -143.0 to 653.0	23.5 ng/mL Interval -90.0 to 460.0
Change From Baseline in hsCRP, SP-D, and Clara Cell Protein 16 (CC 16) Levels in Serum at Week 12 SP-D	-0.10 ng/mL Interval -15.7 to 11.0	-0.20 ng/mL Interval -7.9 to 4.6
Change From Baseline in hsCRP, SP-D, and Clara Cell Protein 16 (CC 16) Levels in Serum at Week 12 CC-16	-0.05 ng/mL Interval -0.6 to 0.4	-0.05 ng/mL Interval -1.2 to 0.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Per Protocol Amendment 4, the measurement of fibrinogen levels in serum was removed from the analysis plan because fibrinogen levels were found to be too low and too difficult to measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. Respiratory function tests were performed for the measurement of FEV1 and FVC at Baseline and at Week 12. The values were measured at 15 to 60 minutes following the use of a pressurized metered-dose inhaler. Three technically acceptable values were obtained, and the highest value was recorded. Change from Baseline in FEV1 and FVC was calculated as the Week 12 value minus the Baseline value.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Week 12 FEV1	0.035 Liters (L) Interval -0.09 to 0.13	0.020 Liters (L) Interval -0.03 to 0.13
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Week 12 FVC	-0.035 Liters (L) Interval -0.13 to 0.17	-0.055 Liters (L) Interval -0.25 to 0.19

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 1, participants were asked to rate how much they cough on a scale of 0 to 5: 0, "I never cough"; 5, "I cough all the time." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 1 Score at Week 12	0.1 Scores on a scale Standard Deviation 0.89	-0.5 Scores on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 2, participants were asked to rate the amount of phlegm (mucus) in their chest on a scale of 0 to 5: 0, "I have no phlegm (mucus) in my chest at all"; 5, "My chest is completely full of phlegm (mucus)." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 2 Score at Week 12	-0.2 Scores on a scale Standard Deviation 1.33	0.0 Scores on a scale Standard Deviation 1.34

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 3, participants were asked to rate how tight their chest feels on a scale of 0 to 5: 0, "My chest does not feel tight at all"; 5, "My chest feels very tight." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 3 Score at Week 12	0.2 Scores on a scale Standard Deviation 1.03	0.0 Scores on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 4, participants were asked to rate how breathless they feel when walking up a flight of stairs or a hill on a scale of 0 to 5: 0, "When I walk up a hill or one flight of stairs I am not breathless"; 5, "When I walk up a hill or one flight of stairs I am very breathless." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 4 Score at Week 12	-0.7 Scores on a scale Standard Deviation 1.41	0.1 Scores on a scale Standard Deviation 1.11

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 5, participants were asked to rate how limited they are in doing activities at home on a scale of 0 to 5: 0, "I am not limited doing any activities at home"; 5, "I am very limited doing activities at home." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 5 Score at Week 12	0.1 Scores on a scale Standard Deviation 1.11	0.0 Scores on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 6, participants were asked to rate how confident they are leaving home despite their lung condition on a scale of 0 to 5: 0, "I am confident leaving my home despite my lung condition"; 5, "I am not at all confident leaving my home because of my lung condition." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 6 Score at Week 12	-0.1 Scores on a scale Standard Deviation 0.59	0.1 Scores on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 7, participants were asked to rate how soundly they sleep on a scale of 0 to 5: 0, "I sleep soundly"; 5, "I don't sleep soundly because of my lung condition." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 7 Score at Week 12	0.2 Scores on a scale Standard Deviation 1.08	0.0 Scores on a scale Standard Deviation 1.55

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 8, participants were asked to rate how much energy they have on a scale of 0 to 5: 0, "I have lots of energy"; 5, "I have no energy at all." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Question 8 Score at Week 12	-0.1 Scores on a scale Standard Deviation 0.89	0.2 Scores on a scale Standard Deviation 1.06

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per Protocol Population

Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8; each question scored from 0 to 5) designed to assess the health status of participants with COPD. The total score is calculated as the sum of the scores from Questions 1 to 8, for a range of possible scores of 0 to 40. A higher total score represents a lower quality of life, and vice versa. Change from Baseline was calculated as the Week 12 score minus the Baseline score.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Change From Baseline in the COPD Assessment Test (CAT) Total Score at Week 12	-0.5 Scores on a scale Standard Deviation 4.45	-0.2 Scores on a scale Standard Deviation 4.18

SECONDARY outcome

Timeframe: From Baseline up to Week 12

Population: Per Protocol Population

The occurrence of a COPD exacerbation was assessed on each day of evaluation during the treatment period per the defined severity classifications. COPD exacerbations were classified based on severity as a mild exacerbation (exacerbation of COPD symptoms were manageable by the participant, not requiring systemic corticosteroid or antimicrobial therapy), a moderate exacerbation (exacerbation of COPD symptoms required systemic corticosteroid or antimicrobial therapy), or a severe exacerbation (exacerbation of COPD symptoms required hospitalization). The number of participants who experienced 0, 1, 2, and >=3 exacerbation(s) was summarized.

Outcome measures

Measure	Placebo n=26 Participants Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=26 Participants Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 2 overall exacerbations	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 0 moderate exacerbations	25 Participants	26 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 1 moderate exacerbation	1 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 2 moderate exacerbations	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period >=3 moderate exacerbations	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 0 severe exacerbations	26 Participants	26 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 1 severe exacerbation	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 2 severe exacerbations	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period >=3 severe exacerbations	0 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 0 overall exacerbations	25 Participants	26 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period 1 overall exacerbation	1 Participants	0 Participants
Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period >=3 overall exacerbations	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

ADOAIR 250

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=28 participants at risk Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=28 participants at risk Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	7.1% 2/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.

Other adverse events

Measure	Placebo n=28 participants at risk Participants self-administered one inhalation of placebo powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.	ADOAIR 250 n=28 participants at risk Participants self-administered one inhalation of ADOAIR 250 (salmeterol 50 micrograms \[µg\] and fluticasone propionate 250 µg) powder twice daily from a dry powder inhaler for 12 weeks. Participants used oxitropium (a short-acting anticholinergic drug) as a relief medication during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	10.7% 3/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	17.9% 5/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	7.1% 2/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Oral candidiasis	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	7.1% 2/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Pharyngitis	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Rhinitis	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Gastroenteritis	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Influenza	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Tinea pedis	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	17.9% 5/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	7.1% 2/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain lower	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Gastrointestinal disorders Stomatitis	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pityriasis rosea	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Eye disorders Conjunctivitis	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Eye disorders Eyelid oedema	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
General disorders Malaise	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Injury, poisoning and procedural complications Muscle injury	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Nervous system disorders Diabetic neuropathy	0.00% 0/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.6% 1/28 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until the end of follow-up (approximately up to Week 13). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.

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