Chronic Obstructive Pulmonary Disease (COPD)Phase 2NCT00626522

Aclidinium/Formoterol Fixed Combination Dose Finding Study

A Phase 2 study testing Aclidinium bromide and formoterol in people with Chronic Obstructive Pulmonary Disease (COPD), run by AstraZeneca at 9 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The study seeks to determine the optimal dose of the Aclidinium/Formoterol combination for investigation in Phase III clinical trials Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Chronic Obstructive Pulmonary Disease (COPD)
What is being tested?: Aclidinium bromide and formoterol
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 808 participants
Where: 9 sitesin 4 countries
Study dates: Feb 2008to Nov 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult males or non-pregnant, non-lactating females aged between 40 and 80 years old, both inclusive. Women of childbearing potential were allowed to enter the trial only if they used two medically approved contraceptive measures (ie, mechanical and pharmacological).
(A female was considered to be of childbearing potential unless she had a hysterectomy, was at least one year post-menopause or had undergone tubal ligation. All women of childbearing potential were to have a negative serum pregnancy test at the Screening Visit).
Patients with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD 2006 classification (http://www.goldcopd.com).
Current or ex-cigarette smoker with a smoking history of at least 10 pack-years.
Pack-years were calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person had smoked. For example, a person who smoked 40 cigarettes a day and had smoked for 10 years would have had a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).
Patients smoking other tobacco types were not allowed, unless they met the cigarette criterion as well.

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Patients whose Forced Expiratory Volume in 1 second (FEV1) at the Screening Visit measured between 30-45 minutes post inhalation of 400 μg of salbutamol was 30% ≤FEV1 <80% of the predicted normal value (ie, 100 x Post-salbutamol FEV1/Predicted FEV1 <80% and ≥30%). (Predicted normal values used for calculation purposes were to be based on European Community for Steel and Coal predicted values)
Patients whose FEV1/Forced Vital Capacity (FVC) at the Screening Visit measured between 30- 45 minutes post inhalation of 400 μg of salbutamol was <70% (ie, 100 x Post-salbutamol FEV1/FVC <70%).
Patients whose COPD symptoms and FEV1 values at the time of randomisation were stable compared to the Screening Visit, according to the Investigator's medical judgment.
Patients who were eligible and able to participate in the trial and who consented to do so in writing after the purpose and nature of the investigation had been explained.

Who cannot join

History or current diagnosis of asthma, allergic rhinitis or atopy, or exercise-induced bronchospasm.
Eosinophil count ≥600 cells/mm3.
Clinically significant respiratory conditions at the time of Screening Visit defined as:
Use of long-term oxygen therapy >5 h/day,
Known active tuberculosis,
History of interstitial lung or pulmonary thromboembolic disease,

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Pulmonary resection during the past 12 months,
History of life-threatening COPD,
History of bronchiectasis secondary to respiratory diseases others than COPD (eg, cystic fibrosis, Kartagener's syndrome, etc),
Patients who in the Investigator's opinion may have needed to stop or start pulmonary rehabilitation or undergo a thoracotomy during the trial,
Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.
Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.
Clinically significant cardiovascular conditions at the time of Screening Visit defined as:
Myocardial infarction within the previous 6 months,
Unstable arrhythmia which has required changes in the pharmacological therapy or other intervention within the previous 12 months, or newly diagnosed arrhythmia within the previous 3 months.
Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association classification (www.americanheart.org)
Thoracic surgery within the previous 24 months
Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. (However, patients who had a diagnosis of these conditions but without symptoms due to stable concomitant medication for its treatment were allowed to enter trial).
Presence of narrow-angle glaucoma.
History of untoward reactions or known hypersensitivity to inhaled anticholinergics (including aclidinium bromide), β2 adrenergic agonists or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
Life expectancy of less than 1 year.
Prolonged QT interval corrected using Bazett's formula (QTcB) interval (>470 msec) in any of the ECGs performed before randomisation, and/or the use of drugs which may have induced its prolongation.
Clinically relevant abnormalities in laboratory results, ECG parameters (other than QTcB), or physical examination if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD.
Clinically significant diseases other than COPD, which, in the opinion of the Investigator, may have put the patient at risk because of the participation in the trial; or diseases which may have influenced the results of the study or the patient's ability to take part in it.
Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night shift workers were to be excluded).
Patients who intended to use any concomitant medication not permitted by the protocol or who had not undergone the required wash-out period for a particular prohibited medication.
Patients who were unable or unlikely to be cooperative with the study requirements of taking the medication, completion of the Patient Diary and attending the clinic for study visits.
Patients who were unable to properly use a dry powder or pressurised metered-dose inhalers (pMDI) inhaler device and/or to perform acceptable and reproducible spirometry measurements as per the ATS/ERS standards (Standardisation of lung function test, 2005 20).
History of drug and/or alcohol abuse or addiction during the previous 2 years.
Previous participation in another clinical trial with any investigational medicinal product 6 weeks prior to the Screening Visit. (Patients who had participated in a previous clinical trial with aclidinium bromide (Almirall product code LAS34273) were to be allowed to participate in this study provided that the above criterion was fulfilled. This circumstance was to be specifically recorded on the eCRF).

Trial locations and contacts

9 sites in 4 countries.

Country

City, postcode or hospital

9 sites in 4 countries

Russia4 sites

Research Site
Moscow
Research Site
Saint Petersburg
Research Site
Saratov
Research Site
Yaroslavl

Other trials in Russia

Australia2 sites

Research Site
Taichung
Research Site
Taipei

Other trials in Australia

Poland2 sites

Research Site
Saint Petersburg
Research Site
St-Petersburg

Other trials in Poland

Czechia1 site

Research Site
Moscow

Other trials in Czechia

About this study

Official title: A Randomised, 4-week, Placebo-controlled, Double-blind, 6 Arm Parallel Group, Dose-finding Clinical Trial, to Assess the Efficacy, Safety and Pharmacokinetics of Three Different Doses of Formoterol Combined With the Inhaled Anticholinergic Aclidinium Bromide, Aclidinium Bromide Monotherapy and Formoterol Monotherapy All Administrated Once Daily by Inhalation Via Almirall Inhaler in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease.

The study seeks to determine the optimal dose of the Aclidinium/Formoterol combination for investigation in Phase III clinical trials

Read the detailed description

Dose-finding clinical trial, to assess the efficacy, safety and pharmacokinetics of three different doses of formoterol combined with the inhaled anticholinergic aclidinium bromide, aclidinium bromide monotherapy and formoterol monotherapy

Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Being tested: Aclidinium bromide and formoterol, Aclidinium bromide and formoterol placebo
Keywords: Bronchitis, Chronic, Emphysema, Smokers or ex-Smokers
Medical subject headings: Pulmonary Disease, Chronic Obstructive, Bronchitis, Bronchiolitis Obliterans Syndrome, Emphysema, Smoking Cessation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aclidinium bromide and formoterolDrug
once daily
Aclidinium bromide and formoterol placeboDrug
once daily

Study groups in NCT00626522
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: Aclidinium bromide and formoterol
2	Experimental	Not described Receives: Drug: Aclidinium bromide and formoterol
3	Experimental	Not described Receives: Drug: Aclidinium bromide and formoterol
4	Placebo comparator	Not described Receives: Drug: Aclidinium bromide and formoterol placebo
5	Placebo comparator	Not described Receives: Drug: Aclidinium bromide and formoterol placebo
6	Placebo comparator	Not described Receives: Drug: Aclidinium bromide and formoterol placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr
Measured: Baseline and treatment Week 4

Secondary outcomes (4)

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
Measured: Baseline and treatment Week 4
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Measured: Baseline and treatment Week 4
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-3 hr
Measured: Baseline and treatment Week 4
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-6 hr
Measured: Baseline and treatment Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Nov 2008

First posted29 Feb 2008 (estimated)
Study startFeb 2008
Primary completionNov 2008
Study completionNov 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 808 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00626522
Sponsor's protocol ID: M/273FO/23
Other IDs: 2007-004435-30
Status last verified: Sep 2016
First submitted: 21 Feb 2008
Last updated: 16 Nov 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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COPD, Chronic Obstructive Pulmonary Disease (COPD)
Not yet recruitingPhase 3
Study of Fluticasone/Formoterol/Glycopyrronium for the Treatment Chronic Obstructive Pulmonary Disease (TRIPLAR)
Chronic Obstructive Pulmonary Disease
RecruitingObservational study
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All Chronic Obstructive Pulmonary Disease (COPD) trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, 4-week, Placebo-controlled, Double-blind, 6 Arm Parallel Group, Dose-finding Clinical Trial, to Assess the Efficacy, Safety and Pharmacokinetics of Three Different Doses of Formoterol Combined With the Inhaled Anticholinergic Aclidinium Bromide, Aclidinium Bromide Monotherapy and Formoterol Monotherapy All Administrated Once Daily by Inhalation Via Almirall Inhaler in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease.
ClinicalTrials.gov ID: NCT00626522
Acronym / sponsor ID: M/273FO/23
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Bronchitis, Chronic, Emphysema, Smokers or ex-Smokers
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 808 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: Nov 2008 (actual)
Study completion: Nov 2008 (actual)
First posted: 29 Feb 2008 (estimated)
Results: Posted 8 Aug 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study seeks to determine the optimal dose of the Aclidinium/Formoterol combination for investigation in Phase III clinical trials

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
1	Experimental	Drug: Aclidinium bromide and formoterol
2	Experimental	Drug: Aclidinium bromide and formoterol
3	Experimental	Drug: Aclidinium bromide and formoterol
4	Placebo comparator	Drug: Aclidinium bromide and formoterol placebo
5	Placebo comparator	Drug: Aclidinium bromide and formoterol placebo
6	Placebo comparator	Drug: Aclidinium bromide and formoterol placebo

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Adult males or non-pregnant, non-lactating females aged between 40 and 80 years old, both inclusive. Women of childbearing potential were allowed to enter the trial only if they used two medically approved contraceptive measures (ie, mechanical and pharmacological).
(A female was considered to be of childbearing potential unless she had a hysterectomy, was at least one year post-menopause or had undergone tubal ligation. All women of childbearing potential were to have a negative serum pregnancy test at the Screening Visit).
Patients with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD 2006 classification (http://www.goldcopd.com).
Current or ex-cigarette smoker with a smoking history of at least 10 pack-years.
Pack-years were calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person had smoked. For example, a person who smoked 40 cigarettes a day and had smoked for 10 years would have had a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).

Key exclusion criteria (30 listed)

History or current diagnosis of asthma, allergic rhinitis or atopy, or exercise-induced bronchospasm.
Eosinophil count ≥600 cells/mm3.
Clinically significant respiratory conditions at the time of Screening Visit defined as:
Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.
Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aclidinium bromide and formoterolonce daily	Drug	1, 2, 3
Aclidinium bromide and formoterol placeboonce daily	Drug	4, 5, 6

Primary outcome

Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr
Time frame: Baseline and treatment Week 4

4 secondary outcomes

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline and treatment Week 4
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline and treatment Week 4
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-3 hr
Time frame: Baseline and treatment Week 4
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-6 hr
Time frame: Baseline and treatment Week 4

Results and safety

Results posted to the registry on 8 Aug 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aclidinium 200 μg / Formoterol 6 μg	121	115
Aclidinium 200 μg / Formoterol 12 μg	120	113
Aclidinium 200 μg / Formoterol 18 μg	125	117
Aclidinium 200 μg	76	74
Formoterol 12 μg	65	58
Placebo	59	57

Primary outcome: Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr

Time frame: Baseline and treatment Week 4. Least squares mean (95% Confidence Interval). Unit: Liters

Measure	Aclidinium 200 μg / Formoterol 6 μg n = 112	Aclidinium 200 μg / Formoterol 12 μg n = 111	Aclidinium 200 μg / Formoterol 18 μg n = 115	Aclidinium 200 μg n = 71	Formoterol 12 μg n = 54	Placebo n = 55
Value	0.170 (0.128 to 0.213)	0.219 (0.176 to 0.262)	0.230 (0.187 to 0.273)	0.075 (0.021 to 0.129)	0.099 (0.037 to 0.161)	-0.036 (-0.097 to 0.025)

Aclidinium 200 μg / Formoterol 6 μg vs Placebo: Least squares mean difference: 0.206 (95% CI 0.131 to 0.280), p <0.0001, ANCOVA
Aclidinium 200 μg / Formoterol 12 μg vs Placebo: Least squares mean difference: 0.254 (95% CI 0.180 to 0.329), p <0.0001, ANCOVA
Aclidinium 200 μg / Formoterol 18 μg vs Placebo: Least squares mean difference: 0.265 (95% CI 0.191 to 0.340), p <0.0001, ANCOVA

Population analysed: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 38. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aclidinium 200 μg / Formoterol 6 μg	1 of 121 (0.8%)	2 of 121 (1.7%)	Not reported
Aclidinium 200 μg / Formoterol 12 μg	1 of 120 (0.8%)	1 of 120 (0.8%)	Not reported
Aclidinium 200 μg / Formoterol 18 μg	3 of 125 (2.4%)	3 of 125 (2.4%)	Not reported
Aclidinium 200 μg	0 of 76 (0%)	4 of 76 (5.3%)	Not reported
Formoterol 12 μg	1 of 65 (1.5%)	5 of 65 (7.7%)	Not reported
Placebo	0 of 59 (0%)	2 of 59 (3.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Sponsor websiteLink provided by the sponsor.
CSR SynopsisLink provided by the sponsor.

Related trials for Chronic Obstructive Pulmonary Disease (COPD)

Recruiting
Lungs on Fire: Wildfire Smoke, Incident Diseases, Susceptible Populations, and Community Values in Canada
Asthma, Chronic Obstructive Pulmonary Disease (COPD)
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
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Not yet recruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Esther Garcia, MD study director

AstraZeneca

9 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aclidinium bromide and formoterol in people with Chronic Obstructive Pulmonary Disease (COPD), run by AstraZeneca at 9 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Russia, Australia, Poland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr (time frame: Baseline and treatment Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00626522.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2016.