Trial Outcomes & Findings for Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease (NCT NCT01509677)

NCT ID: NCT01509677

Last Updated: 2019-11-29

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 158 participants
• Primary outcome timeframe: 16 weeks
• Results posted on: 2019-11-29

Participant Flow

Participant milestones

Measure	R500 Roflumilast 500 µg	Placebo Placebo to Roflumilast
Overall Study STARTED	79	79
Overall Study COMPLETED	76	73
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	R500 n=79 Participants Roflumilast 500 µg	Placebo n=79 Participants Placebo to Roflumilast	Total n=158 Participants Total of all reporting groups
Age, Continuous	64 Years STANDARD_DEVIATION 8.23 • n=5 Participants	62.5 Years STANDARD_DEVIATION 8.43 • n=7 Participants	63.2 Years STANDARD_DEVIATION 8.34 • n=5 Participants
Age, Customized Between 18 and 65 years	37 Participants n=5 Participants	46 Participants n=7 Participants	83 Participants n=5 Participants
Age, Customized >=65 years	42 Participants n=5 Participants	33 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	77 Participants n=5 Participants	77 Participants n=7 Participants	154 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Europe	79 Participants n=5 Participants	79 Participants n=7 Participants	158 Participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: The CD8+ cells count results in submucosa for the primary outcome were available for 117 patients at V2 (41 missing) and 114 patients at V6 (44 missing). The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See section 11.4.1 in CSR

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.	442.4 CD8+ cells count Standard Deviation 312.74 • Interval 0.82 to 1.3	427.1 CD8+ cells count Standard Deviation 261.42

PRIMARY outcome

Timeframe: Baseline to 16 weeks

Population: The CD8+ cells count results in submucosa for the primary outcome were available for 117 patients at V2 (41 missing) and 114 patients at V6 (44 missing). The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See section 11.4.1 in CSR

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue	13.4 cells/mm^2 Standard Deviation 302.69	29.4 cells/mm^2 Standard Deviation 298.88

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
CD68+ Count in Biopsied Material (Submucosa)	149.1 CD68+ Count Standard Deviation 113.91	124.4 CD68+ Count Standard Deviation 93.15

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

CD68+ Cell Count in Biopsied Material (submucosa): Poisson regression (ratio). Clarification: Measure type described as "Number" refers to "Risk of each treatment group". It is not possible to select "risk" from this template so "number" was selected instead. This issue applies to similar variables reporting poisson regression.

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)	126.8 CD68+ Cell Count NA	121.6 CD68+ Cell Count NA

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)	6.1 CD68+ Cell Count (cells/mm^2) Standard Error 10.99	-5.3 CD68+ Cell Count (cells/mm^2) Standard Error 11.05

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

CD4+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Risk of each treatment group".

Outcome measures

Measure	R500 n=48 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model	304.6 CD4+ Cell Counts NA	255.0 CD4+ Cell Counts NA

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

CD45+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "treatment risk"

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model	818.4 CD45+ Cell Counts NA	960.3 CD45+ Cell Counts NA

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

Neutrophils Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Treatment risk"

Outcome measures

Measure	R500 n=49 Participants Roflumilast 500 µg	Placebo n=46 Participants Placebo to Roflumilast
Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model	118.6 Neutrophils Cell Counts NA	127.7 Neutrophils Cell Counts NA

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

CD8+ Cell Count in biopsied material (Bronchial Epithelium): poisson regression model. Clarification: Measure Type "Number" refers to "Treatment risk"

Outcome measures

Measure	R500 n=41 Participants Roflumilast 500 µg	Placebo n=37 Participants Placebo to Roflumilast
CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model	422.1 CD8+ Cell Count NA	505.3 CD8+ Cell Count NA

SECONDARY outcome

Timeframe: 16 weeks

Population: The reason for missing samples was that the sample amount did not reach the minimal area requested per study protocol. See 11.4.7 in CSR

CD68+ Cell Count in biopsied material (Bronchial Epithelium):poisson regression model. Clarification: Measure type "Number" refers to "Treatment Risk"

Outcome measures

Measure	R500 n=39 Participants Roflumilast 500 µg	Placebo n=32 Participants Placebo to Roflumilast
CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model	76.3 CD68+ Cell Count NA	93.1 CD68+ Cell Count NA

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=43 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference	1.7181 10^6 neutrophils/mL Standard Error 1.64471	0.0827 10^6 neutrophils/mL Standard Error 1.61220

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=43 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference	0.1017 10^6 macrophages/mL Standard Error 0.23396	-0.3710 10^6 macrophages/mL Standard Error 0.22970

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=43 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference	-0.0986 10^6 eosinophils/mL Standard Error 0.02639	-0.0360 10^6 eosinophils/mL Standard Error 0.02585

SECONDARY outcome

Timeframe: BAseline to 14 weeks

Outcome measures

Measure	R500 n=43 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference	-0.0167 10^6 lymphocytes/mL Standard Error 0.01167	-0.0060 10^6 lymphocytes/mL Standard Error 0.01141

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=45 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)	2.527 10^6 neutrophils/mL Standard Error 2.3571	0.382 10^6 neutrophils/mL Standard Error 2.3535

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=45 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)	0.315 10^6 macrophages/mL Standard Error 2.1328	-0.826 10^6 macrophages/mL Standard Error 2.1316

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=45 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)	-1.826 10^6 eosinophils/m Standard Error 0.5214	-0.041 10^6 eosinophils/m Standard Error 0.5200

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=45 Participants Roflumilast 500 µg	Placebo n=44 Participants Placebo to Roflumilast
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)	-0.137 10^6 lymphocytes)/mL Standard Error 0.1332	-0.086 10^6 lymphocytes)/mL Standard Error 1.329

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=54 Participants Roflumilast 500 µg	Placebo n=57 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL))	-0.32 µg/mL Standard Error 0.730	-0.48 µg/mL Standard Error 0.700

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=54 Participants Roflumilast 500 µg	Placebo n=56 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))	-827.3 pg/mL Standard Error 1995.79	-1538.4 pg/mL Standard Error 1941.08

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=55 Participants Roflumilast 500 µg	Placebo n=57 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))	80.1 ng/mL Standard Error 57.07	-8.4 ng/mL Standard Error 55.44

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=53 Participants Roflumilast 500 µg	Placebo n=57 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL))	-95.2 pg/mL Standard Error 49.23	-69.3 pg/mL Standard Error 46.93

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=54 Participants Roflumilast 500 µg	Placebo n=57 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL))	25.87 ng/mL Standard Error 13.085	-1.92 ng/mL Standard Error 12.551

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=55 Participants Roflumilast 500 µg	Placebo n=57 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL))	253.1 pg/mL Standard Error 89.46	-43.7 pg/mL Standard Error 86.84

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL))	-0.05 µg/mL Standard Error 0.061	-0.05 µg/mL Standard Error 0.062

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))	-4.48 pg/mL Standard Error 0.929	-3.92 pg/mL Standard Error 0.945

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))	0.8 ng/mL Standard Error 0.78	-1.0 ng/mL Standard Error 0.79

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL))	-24.8 pg/mL Standard Error 11.0	-23.4 pg/mL Standard Error 11.21

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL))	2.7 ng/mL Standard Error 3.19	-7.5 ng/mL Standard Error 3.25

SECONDARY outcome

Timeframe: Baseline to 14 weeks

Outcome measures

Measure	R500 n=68 Participants Roflumilast 500 µg	Placebo n=66 Participants Placebo to Roflumilast
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL))	11.3 pg/mL Standard Error 12.80	-21.5 pg/mL Standard Error 13.08

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Outcome measures

Measure	R500 n=77 Participants Roflumilast 500 µg	Placebo n=77 Participants Placebo to Roflumilast
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))	0.028 L Standard Error 0.0212	-0.035 L Standard Error 0.0212

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Outcome measures

Measure	R500 n=77 Participants Roflumilast 500 µg	Placebo n=77 Participants Placebo to Roflumilast
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))	0.031 L Standard Error 0.0391	-0.033 L Standard Error 0.391

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Wilcoxon test is a non-parametric test to evaluate differences among treatments in the variable that is being reported here. The data reported in the outcome measure data table are hodges Lehmann estimate of change from baseline in FEV1/FVC ratio.

Outcome measures

Measure	R500 n=77 Participants Roflumilast 500 µg	Placebo n=77 Participants Placebo to Roflumilast
Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC	0.5 ratio Interval 0.0 to 1.0	-0.5 ratio Interval -1.0 to 0.5

Adverse Events

R500

Serious events: 8 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	R500 n=79 participants at risk Roflumilast 500 µg	Placebo n=79 participants at risk Placebo to Roflumilast
Congenital, familial and genetic disorders Hydrocele	0.00% 0/79 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Gastrointestinal disorders Dyspepsia	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
General disorders Incarcerated hernia	0.00% 0/79 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Infections and infestations Diverticulitis	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Infections and infestations Pneumonia	0.00% 0/79 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Investigations Influenza A virus test positive	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Musculoskeletal and connective tissue disorders Synovial cyst	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Psychiatric disorders Depression	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Reproductive system and breast disorders Spermatocele	0.00% 0/79 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Respiratory, thoracic and mediastinal disorders COPD	3.8% 3/79 • Number of events 3 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 1/79 • Number of events 1 • 16 weeks	0.00% 0/79 • 16 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/79 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks

Other adverse events

Measure	R500 n=79 participants at risk Roflumilast 500 µg	Placebo n=79 participants at risk Placebo to Roflumilast
Gastrointestinal disorders Diarrhoea	13.9% 11/79 • Number of events 11 • 16 weeks	5.1% 4/79 • Number of events 4 • 16 weeks
Gastrointestinal disorders Dry mouth	0.00% 0/79 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks
Gastrointestinal disorders Nausea	7.6% 6/79 • Number of events 6 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Gastrointestinal disorders Vomiting	6.3% 5/79 • Number of events 5 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
General disorders Fatigue	3.8% 3/79 • Number of events 3 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks
Infections and infestations Eye infection	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Infections and infestations Herpes zoster	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Infections and infestations Influenza	0.00% 0/79 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Infections and infestations Nasopharyngitis	16.5% 13/79 • Number of events 14 • 16 weeks	15.2% 12/79 • Number of events 15 • 16 weeks
Infections and infestations Rhinitis	3.8% 3/79 • Number of events 3 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks
Infections and infestations Urinary tract infection	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Infections and infestations Viral infection	0.00% 0/79 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Injury, poisoning and procedural complications Laceration	0.00% 0/79 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Injury, poisoning and procedural complications Procedural pain	3.8% 3/79 • Number of events 3 • 16 weeks	0.00% 0/79 • 16 weeks
Investigations Forced expiratory volume decreased	0.00% 0/79 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks
Investigations Weight decreased	7.6% 6/79 • Number of events 6 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Investigations White blood cell count increased	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Metabolism and nutrition disorders Decreased appetite	2.5% 2/79 • Number of events 2 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Musculoskeletal and connective tissue disorders Back pain	6.3% 5/79 • Number of events 5 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Musculoskeletal and connective tissue disorders Muscle spasms	2.5% 2/79 • Number of events 2 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Musculoskeletal and connective tissue disorders Myalgia	3.8% 3/79 • Number of events 5 • 16 weeks	0.00% 0/79 • 16 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Musculoskeletal and connective tissue disorders Synovial cyst	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Nervous system disorders Dizziness	3.8% 3/79 • Number of events 3 • 16 weeks	0.00% 0/79 • 16 weeks
Nervous system disorders Haedache	5.1% 4/79 • Number of events 4 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks
Nervous system disorders Lethargy	3.8% 3/79 • Number of events 4 • 16 weeks	0.00% 0/79 • 16 weeks
Nervous system disorders Tremor	3.8% 3/79 • Number of events 3 • 16 weeks	0.00% 0/79 • 16 weeks
Psychiatric disorders Insomnia	8.9% 7/79 • Number of events 7 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Respiratory, thoracic and mediastinal disorders Bronchial polyp	1.3% 1/79 • Number of events 1 • 16 weeks	2.5% 2/79 • Number of events 2 • 16 weeks
Respiratory, thoracic and mediastinal disorders COPD	11.4% 9/79 • Number of events 10 • 16 weeks	15.2% 12/79 • Number of events 13 • 16 weeks
Respiratory, thoracic and mediastinal disorders Cough	12.7% 10/79 • Number of events 11 • 16 weeks	15.2% 12/79 • Number of events 12 • 16 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.8% 3/79 • Number of events 3 • 16 weeks	1.3% 1/79 • Number of events 1 • 16 weeks
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.8% 3/79 • Number of events 4 • 16 weeks	0.00% 0/79 • 16 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 2/79 • Number of events 2 • 16 weeks	0.00% 0/79 • 16 weeks
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/79 • 16 weeks	2.5% 2/79 • Number of events 3 • 16 weeks
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.3% 1/79 • Number of events 1 • 16 weeks	3.8% 3/79 • Number of events 3 • 16 weeks

Additional Information

AstraZeneca Clinical Study Information Center

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place