Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
COPD
Brief summary
The aim of the present study is to evaluate the effect of aclidinium bromide 400 μg BID compared with placebo on COPD symptoms in a symptomatic patients population with moderate COPD and chronic bronchitis, and particularly assess the effects in cough by using specific tools to assess the occurrence and impact of this relevant COPD symptom.
Interventions
Inhaled Aclidinium 400 μg twice per day by Eklira Genuair Inhaler
DRUGPlacebo
Inhaled dose-matched placebo, twice per day by Eklira Genuair Inhaler
Sponsors
Menarini Group
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
1. Adult male or non-pregnant, non-lactating female aged ≥40. Women of childbearing potential will follow specific study requirements. 2. Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years 3. Patients with a clinical diagnosis of moderate COPD, with a post bronchodilator test available within 6 months prior to Visit 1 (Screening), with FEV1 ≥50% and \<80% and FEV1/FVC \<70%. 4. Symptomatic patients with a CAT≥10 at Screening and Randomisation Visit (Visit 1 and 2) 5. Clinical Diagnosis of Chronic Bronchitis (defined as presence of cough and sputum production for at least 3 months in each of 2 consecutive years) 6. Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained
Exclusion criteria
1. History or current diagnosis of asthma. 2. Patients who suffered from a moderate or severe COPD exacerbation in the last year prior to Visit 1 (Screening) or during the run-in period. 3. Patients who develop a respiratory tract infection within 6 weeks before Visit 1 (Screening) or during the run-in period. 4. Clinically significant respiratory and cardiovascular conditions thought to be contributing to cough or likely to interfere in the conduct of the study. 5. Patient who in the investigator's opinion may need to start a pulmonay rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening Visit. 6. Use of long-term oxygen therapy. 7. Patients in non-stable treatment with angiotensin-converting enzyme inhibitors or opiates. 8. Patients in treatment with mucolytics, antihistamines, expectorants or antitussive drugs including over-the-counter medication. 9. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers. 10. Patient with clinically relevant abnormalities in the results of the physical examination at Visit 1 (Screening) 11. Patient with a history of hypersensitivity reaction to inhaled anticholinergics,sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm). 12. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy. 13. Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis 14. Current diagnosis of cancer other than basal or squamous cell skin cancer 15. Patient with any other serious or uncontrolled physical or mental dysfunction 16. Patient with a history (within 2 years prior to Screening Visit) of drug and/or alcohol abuse that may prevent study compliance based on investigator judgment. 17. Patient unlikely to be cooperative or that can not comply with the study procedures 18. Patient treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Visit 1 (Screening). 19. Patient who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required stabilization periods for prohibited medication. 20. Any other conditions that, in the investigator's opinion, might indicate the patient to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Overall Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) Total Score Over the 8 Week Study Period | Baseline to Week 8 | The EXACT-Respiratory Symptoms (E-RS) questionnaire was completed every evening The E-RS scale is an instrument comprising a subset of EXACT items to test the effect of treatment on the severity of respiratory symptoms in stable COPD Eleven of the 14-items of the EXACT questionnaire provides information about COPD symptoms: The E-RS Total Score is an aggregate of three domains: chest symptoms (derived sum of 3 items), cough and sputum (derived sum of 3 items) and RS-breathlessness (derived sum of 4 items); Individual scores were rated from 0 to 4 The E-RS Total score is based on a logit scoring system with conversion to a 0 (lowest score) to 100 scale (highest score) with higher scores indicating more severe symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Overall E-RS Cough and Sputum Domain Score Over the 8 Week Study Period | Baseline to Week 8 | The scale range of the 'cough and sputum' domain of the E-RS was 0-11, with higher scores indicating more severe symptoms |
| Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 8 | Week 8 | The LCQ is a self-administered questionnaire that assesses cough related quality of life The LCQ comprises 19 items and 3 domains (physical, psychological and social) The total score ranges from 3 to 21 and each domain scores range from 1 to 7; a higher score indicates a better quality of life |
Countries
Germany, Hungary, Italy, Spain, United Kingdom
Participant flow
Recruitment details
Patients were randomized in 30 study sites in 5 countries Germany (10 sites), Hungary (6), Italy (2), Spain (9) and the United Kingdom (3) First patient was enrolled in March 2015 and last patient last visit was in November 2015
Pre-assignment details
300 patients were screened; 269 were assessed as eligible and were randomized into the study Thirty-one patients failed screening, with the main reason for screening failure being non-fulfilment of the inclusion or exclusion criteria (24 patients)
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium 400 μg Aclidinium bromide 400 μg BID administered by Genuair® multidose dry powder inhaler | 135 |
| Placebo Placebo BID administered by Genuair® multidose dry powder inhaler | 134 |
| Total | 269 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Aclidinium 400 μg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.0 Years STANDARD_DEVIATION 8.4 | 62.0 Years STANDARD_DEVIATION 9.1 | 62.0 Years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 57 Participants | 50 Participants | 107 Participants |
| Sex: Female, Male Male | 78 Participants | 84 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 135 | 20 / 134 |
| serious Total, serious adverse events | 2 / 135 | 2 / 134 |
Outcome results
Primary
Change From Baseline in Overall Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) Total Score Over the 8 Week Study Period
The EXACT-Respiratory Symptoms (E-RS) questionnaire was completed every evening The E-RS scale is an instrument comprising a subset of EXACT items to test the effect of treatment on the severity of respiratory symptoms in stable COPD Eleven of the 14-items of the EXACT questionnaire provides information about COPD symptoms: The E-RS Total Score is an aggregate of three domains: chest symptoms (derived sum of 3 items), cough and sputum (derived sum of 3 items) and RS-breathlessness (derived sum of 4 items); Individual scores were rated from 0 to 4 The E-RS Total score is based on a logit scoring system with conversion to a 0 (lowest score) to 100 scale (highest score) with higher scores indicating more severe symptoms
Time frame: Baseline to Week 8
Population: Intent to treat (ITT) population defined as all randomized patients who took at least one dose of investigational medicinal product E-RS data were available for 131/135 patients receiving aclidinium and 133/134 receiving placebo
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium 400 μg | Change From Baseline in Overall Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) Total Score Over the 8 Week Study Period | -1.75 Score | Standard Error 0.342 |
| Placebo | Change From Baseline in Overall Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) Total Score Over the 8 Week Study Period | -0.73 Score | Standard Error 0.342 |
p-value: 0.030695% CI: [-1.94, -0.1]Mixed Models Analysis
Secondary
Change From Baseline in Overall E-RS Cough and Sputum Domain Score Over the 8 Week Study Period
The scale range of the 'cough and sputum' domain of the E-RS was 0-11, with higher scores indicating more severe symptoms
Time frame: Baseline to Week 8
Population: Intent to treat (ITT) population defined as all randomized patients who took at least one dose of investigational medicinal product E-RS data were available for 131/135 patients receiving aclidinium and 133/134 receiving placebo
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium 400 μg | Change From Baseline in Overall E-RS Cough and Sputum Domain Score Over the 8 Week Study Period | -0.54 Score | Standard Error 0.09 |
| Placebo | Change From Baseline in Overall E-RS Cough and Sputum Domain Score Over the 8 Week Study Period | -0.33 Score | Standard Error 0.09 |
p-value: 0.079395% CI: [-0.46, 0.03]Mixed Models Analysis
Secondary
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 8
The LCQ is a self-administered questionnaire that assesses cough related quality of life The LCQ comprises 19 items and 3 domains (physical, psychological and social) The total score ranges from 3 to 21 and each domain scores range from 1 to 7; a higher score indicates a better quality of life
Time frame: Week 8
Population: Intent to treat (ITT) population defined as all randomized patients who took at least one dose of investigational medicinal product LCQ data were available for 126/135 patients receiving aclidinium and 128/134 receiving placebo
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium 400 μg | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 8 | 1.18 Score | Standard Error 0.214 |
| Placebo | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 8 | 1.24 Score | Standard Error 0.214 |
p-value: 0.84495% CI: [-0.64, 0.52]Mixed Models Analysis