Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD
Brief summary
The present trial is conducted to further assess the efficacy by means of serial spirometry, safety and tolerability of three doses of aclidinium bromide administered twice a day compared to previously approved BID drug, formoterol 12 µg, and placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).after 7 days on treatment. Every treatment period is 7-days long and there is a 5 to 7-days wash-out period in between them. The trial starts with a run in phase of 11 to 17-days duration and it ends up with a follow up contact 14-days after last treatment dose.
Interventions
DRUGAclidinium bromide 100 μg bid
Aclidinium bromide 100 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
Aclidinium bromide 200 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
DRUGAclidininum bromide 400 μg bid
Aclidinium bromide 400 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days
DRUGPlacebo
Placebo via inhalation in the morning and evening for 7 days
DRUGFormoterol 12 μg bid
Formoterol 12 μg twice-daily via inhalation by Aerolizer® dry powder inhaler: 1 puff in the morning and evening for 7 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and non-pregnant, non-lactating females aged ≥ 40. 2. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines: (http://www.goldcopd.com) and stable airway obstruction. Post-salbutamol FEV1/FVC \< 70% at Screening Visit (Visit 1) (i.e., 100xpost-salbutamol FEV1/FVC \<70%). 3. Current, or ex-cigarette smoker with a smoking history of at least 10 pack-years. 4. Patient whose FEV1 at the Screening Visit measured between 10-15 minutes post inhalation of salbutamol is 30% \< FEV1 \<80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 must be \< 80% and ≥ 30%). 5. Female patients at least 1 year post-menopausal, surgically sterile (defined as having a hysterectomy or tubal ligation), or practicing a medically approved and highly effective method of contraception. 6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent.
Exclusion criteria
1. History or current diagnosis of asthma. 2. Clinically significant respiratory conditions other than COPD at the time of Inform Consent signature 3. Hospitalisation due to COPD exacerbation within the previous 3 months. 4. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract) within the previous 6 weeks. 5. Clinically significant cardiovascular conditions 6. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. 7. Presence of narrow-angle glaucoma. 8. QTcB) above 470 milliseconds in the ECG performed at Screening Visit, 9. Patient who does not maintain regular day/night, waking/sleeping cycles
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | Day 7 |
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | Day 7 |
| Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | Day 7 |
Countries
Belgium, Germany
Participant flow
Recruitment details
This study was conducted at a total of 11 centres; 10 in Germany and 1 in Belgium. The first patient was screened in Apr 2010 and the last patient visit was in Aug 2010.
Pre-assignment details
Patients fulfilling inclusion/exclusion criteria at the time of the Screening Visit were entered into a run-in period of 14 ± 3 days to assess patient's disease stability.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population All patients randomized into the crossover study | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 1 | 0 | 1 |
| Treatment Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Adverse Event | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 3 | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 3 | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 3 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 4 | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 5 | Adverse Event | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants |
| Age, Continuous | 61.1 years STANDARD_DEVIATION 8.5 |
| Gender Female | 20 Participants |
| Gender Male | 59 Participants |
| Region of Enrollment Belgium | 3 participants |
| Region of Enrollment Germany | 76 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 73 | 4 / 73 | 5 / 74 | 2 / 74 | 1 / 76 |
| serious Total, serious adverse events | 0 / 73 | 1 / 73 | 1 / 74 | 0 / 74 | 2 / 76 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment
Time frame: Day 7
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 100 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | 0.128 Liters | Standard Error 0.022 |
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | 0.151 Liters | Standard Error 0.022 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | 0.183 Liters | Standard Error 0.022 |
| Formoterol 12 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | 0.184 Liters | Standard Error 0.022 |
| Placebo | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment | -0.026 Liters | Standard Error 0.022 |
Secondary
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment
Time frame: Day 7
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 100 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | 0.088 Liters | Standard Error 0.021 |
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | 0.100 Liters | Standard Error 0.021 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | 0.133 Liters | Standard Error 0.021 |
| Formoterol 12 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | 0.163 Liters | Standard Error 0.021 |
| Placebo | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment | -0.062 Liters | Standard Error 0.021 |
Secondary
Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment
Time frame: Day 7
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 100 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | 0.044 Liters | Standard Error 0.021 |
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | 0.047 Liters | Standard Error 0.021 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | 0.086 Liters | Standard Error 0.021 |
| Formoterol 12 μg Bid | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | 0.141 Liters | Standard Error 0.021 |
| Placebo | Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment | -0.103 Liters | Standard Error 0.021 |
Secondary
Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment
Time frame: Day 7
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 100 μg Bid | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | 0.081 Liters | Standard Error 0.023 |
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | 0.089 Liters | Standard Error 0.023 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | 0.130 Liters | Standard Error 0.023 |
| Formoterol 12 μg Bid | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | 0.123 Liters | Standard Error 0.023 |
| Placebo | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment | -0.025 Liters | Standard Error 0.023 |