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Aclidinium/Formoterol Fixed Combination Dose Finding Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00626522
First received: February 21, 2008
Last updated: June 28, 2016
Last verified: June 2016
  Purpose
The study seeks to determine the optimal dose of the Aclidinium/Formoterol combination for investigation in Phase III clinical trials

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: Aclidinium bromide and formoterol
Drug: Aclidinium bromide and formoterol placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr [ Time Frame: Treatment Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Treatment Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Treatment Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-3 hr [ Time Frame: Treatment Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-6 hr [ Time Frame: Treatment Week 4 ] [ Designated as safety issue: No ]

Enrollment: 808
Study Start Date: February 2008
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Aclidinium bromide and formoterol
once daily
Experimental: 2 Drug: Aclidinium bromide and formoterol
once daily
Experimental: 3 Drug: Aclidinium bromide and formoterol
once daily
Placebo Comparator: 4 Drug: Aclidinium bromide and formoterol placebo
once daily
Placebo Comparator: 5 Drug: Aclidinium bromide and formoterol placebo
once daily
Placebo Comparator: 6 Drug: Aclidinium bromide and formoterol placebo
once daily

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
  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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).

  2. 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).
  3. 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.

  4. 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)
  5. 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%).
  6. 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.
  7. 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.

Exclusion Criteria:

  1. History or current diagnosis of asthma, allergic rhinitis or atopy, or exercise-induced bronchospasm.
  2. Eosinophil count ≥600 cells/mm3.
  3. 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,
    • 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,
  4. Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.
  5. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.
  6. 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
  7. 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).
  8. Presence of narrow-angle glaucoma.
  9. 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).
  10. Life expectancy of less than 1 year.
  11. 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.
  12. 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.
  13. 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.
  14. Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night shift workers were to be excluded).
  15. 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.
  16. 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.
  17. 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).
  18. History of drug and/or alcohol abuse or addiction during the previous 2 years.
  19. 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626522

Locations
Australia
Research Site
Brasov, Australia
Czech Republic
Research Site
Moscow, Czech Republic
Poland
Research Site
Saint Petersburg, Poland
Research Site
St. Petersburg, Poland
Russian Federation
Research Site
Moscow, Russian Federation
Research Site
Saint Petersburg, Russian Federation
Research Site
Saint-Petersburg, Russian Federation
Research Site
Saratov, Russian Federation
Research Site
Yaroslavl, Russian Federation
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Esther Garcia, MD AstraZeneca
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00626522     History of Changes
Other Study ID Numbers: M/273FO/23  2007-004435-30 
Study First Received: February 21, 2008
Results First Received: June 28, 2016
Last Updated: June 28, 2016
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by AstraZeneca:
Bronchitis
Chronic
Emphysema
Smokers or ex-Smokers

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Formoterol Fumarate
Bromides
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants

ClinicalTrials.gov processed this record on September 28, 2016