Efficacy and Safety Study of Two Fixed-dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Aclidinium 400 μg / Formoterol 12 μg; Aclidinium 400 μg / Formoterol 6 μg; Aclidinium 400 μg; Formoterol 12 μg; Placebo
Intervention description: Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods.; Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods.; Aclidinium bromide 400 μg administered twice-daily (BID) for a 14 day period within four different treatment periods.; Formoterol fumarate 12 μg twice-daily for a 14 day period within four different treatment periods.; Placebo twice-daily delivered by inhalation for a 14 day period within four different treatment periods.
Intervention MeSH terms: Formoterol Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 128.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; COPD; Chronic Bronchitis; Emphysema; Airflow Obstruction, Chronic; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease

Summary:

      The purpose of this study is to evaluate the efficacy of this multicenter, randomized,
      double-blind, placebo-controlled, 4-period, incomplete-block crossover, dose-ranging study
      comparing 2 fixed dose combinations (FDCs) of aclidinium bromide with formoterol fumarate or
      with placebo, aclidinium bromide and formoterol fumarate, all administered twice a day (BID)
      in patients with stable, moderate to severe chronic obstructive pulmonary disease (COPD)
      beginning with a 2-week run-in period and with a 7-10 day washout each between treatment
      period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand the study procedures and be willing to participate in the study as
             indicated by signing the ICF and HIPAA form

          -  Be male or female aged 40 to 80 years, inclusive

          -  Have a diagnosis of stable, moderate to severe COPD (stages II and III) as defined by
             guidelines of the Global Initiative for Chronic Obstructive Lung Disease (2008)

          -  Be a current or former cigarette smoker with a smoking history of at least 10
             pack-years

          -  Have post-albuterol/salbutamol FEV1 values ≥ 30% and < 80% of the predicted value.
             FEV1 will be measured at the Screening Visit (Visit 1) between 10 and 15 minutes after
             inhalation of albuterol/salbutamol.

          -  Have post-albuterol/salbutamol FEV1/FVC values < 70% (ie, 100 × post-
             albuterol/salbutamol FEV1/FVC < 70%).

          -  If female, be at least 1 year postmenopausal or surgically sterile (defined as having
             a hysterectomy or tubal ligation). Women of childbearing potential must have a
             negative serum β-human chorionic gonadotropin pregnancy test at screening

          -  Be in good stable health (as judged by the Investigator) other than the COPD, based on
             medical history, physical examination, ECG, spirometry, and clinical laboratory data
             evaluations

          -  Have COPD symptoms and FEV1 values at the time of randomization that are stable
             compared with those at Screening (Visit 1), according to the Investigator's medical
             judgment

        Exclusion Criteria:

          -  Have been hospitalized for an acute COPD exacerbation within 3 months before screening

          -  Have any respiratory tract infection (including the upper respiratory tract) or signs
             of a COPD exacerbation or respiratory infection in the 6 weeks before Screening (Visit
             1).

          -  Have any clinically significant respiratory conditions other than COPD

          -  Have a history or presence of asthma verified from medical records

          -  Have used theophylline (including long-acting theophylline) within the previous 3
             months before study entry

          -  Have Stage II hypertension, defined as systolic pressure of 160 and above, and
             diastolic pressure of 100 and above

          -  Chronic use of oxygen therapy ≥ 15 hours a day

          -  Have a history, current diagnosis, or presence of exercise-induced bronchospasm

          -  Have a body mass index ≥ 40 kg/m2

          -  Have participated in an pulmonary rehabilitation program within the previous 3 months

          -  Have clinically significant cardiovascular conditions

          -  Have uncontrolled infection resulting from human immunodeficiency virus and/or active
             hepatitis

          -  Have symptomatic prostatic hypertrophy and/or bladder neck obstruction.

          -  Have narrow-angle glaucoma

          -  Have a history of hypersensitivity reaction (including report of paradoxical
             bronchospasm) to inhaled anticholinergics (including aclidinium bromide), β2
             adrenergic agonists, or any other inhaled medication or any component thereof

          -  Have a QTcB, as indicated in the centralized reading report, above 470 msec in the
             resting ECGs performed at Screening (Visit 1) and/or patients who are using
             medications that may prolong the QT interval

          -  Have clinically relevant abnormalities in the results of clinical laboratory tests, in
             ECG parameters other than QTc, in results of the physical examination,

          -  Have any concurrent medical condition that, in the judgment of the Investigator, might
             interfere with the conduct of the study, confound the interpretation of the study
             results, or endanger the patient's well-being

          -  Do not maintain regular day/night, waking/sleeping cycles (eg, patients with history
             of sleep apnea syndrome or any disease related with sleep disturbances such as
             restless legs syndrome or somnambulism)