Advair HFA For Chronic Obstructive Pulmonary Disease(COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Fluticasone Propionate/Salmeterol DISKUS 250/50mcg; Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a MDI 230/42mcg
Intervention description: treatment drug; treatment drug
Intervention MeSH terms: Fluticasone; Xhance; Norflurane; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 247.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: DISKUS; Salmeterol; Fluticasone Propionate; Chronic Obstructive Pulmonary Disease (COPD); Hydroflouroalkane; COPD; HFA MDI

Summary:

      The purpose of this study is to evaluate the efficacy and safety of the FSC HFA MDI in
      subjects with COPD. The dose of FSC HFA MDI to be evaluated corresponds to the dose of FSC
      DISKUS (250/50mcg twice-daily) that is indicated for the treatment of COPD associated with
      chronic bronchitis in the US. This study will last up to approximately 15 weeks, and subjects
      will visit the clinic 5 times. Subjects will be given breathing tests and will record their
      peak expiratory flow measurements daily on diary cards. All study related medicines and
      medical examinations will be provided at no cost. The FSC HFA MDI used in this study has been
      approved by FDA for use in asthma while the FSC 250/50mcg DISKUS has been approved for use in
      asthma and COPD.
    

Eligibility criteria:

        Inclusion criteria:

        Subjects eligible for enrollment in the study must meet all of the following criteria:

          -  Signed and dated written informed consent obtained from the subject and/or subject's
             legally acceptable representative prior to study participation.

          -  Males or females ≥ 40 years of age.

        A female is eligible to participate in this study if she is of:

          1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
             including any female who is post-menopausal [i.e., >1 year without menses in the
             absence of hormone replacement therapy]); or,

          2. child-bearing potential, has a negative pregnancy test (urine) at screen, and one of
             the following applies:

               -  Abstinence from intercourse, or,

               -  Male partner was sterile prior to the female subject's entry into the study, or,

               -  Use of implants of levonorgestrel; or,

               -  Injectable progesterone; or,

               -  Oral contraceptive (combined or progesterone only), contraceptive patch, vaginal
                  ring; or,

               -  Any intrauterine device (IUD) with published data showing that the highest
                  expected failure rate is less than 1% per year (e.g., Paragard), or,

               -  Double barrier technique simultaneously using two of the following: spermicide,
                  male condom, diaphragm, or female condom

                    -  An established clinical history of COPD (including chronic bronchitis and/or
                       emphysema) in accordance with the following definition by the American
                       Thoracic Society:

        COPD is a preventable and treatable disease state characterised by airflow limitation that
        is not fully reversible. The airflow limitation is usually progressive and is associated
        with an abnormal inflammatory response of the lungs to noxious particles or gases,
        primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces
        significant systemic consequences [Celli, 2004].

          -  A post-albuterol FEV1/FVC ratio of ≤ 0.70

          -  A post-albuterol FEV1 ≥ 0.70L and ≤ 70% of predicted normal OR a post-albuterol FEV1
             of ≤ 0.70L and ≥40% of predicted normal but still ≤70% of predicted normal based on
             NHANES III reference values [Hankinson, 1999].

          -  Current or previous smokers with a cigarette smoking history of ≥ 10 pack-years.
             [number of pack years = (number of cigarettes per day / 20) x number of years smoked
             (e.g., 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes
             per day for 20 years]. Former-smokers are defined as subjects who have discontinued
             smoking for ≥ 6 months prior to Visit 1. Subjects who decide to stop smoking at Visit
             1 will not be eligible for participation in the study.

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

          -  A current diagnosis of asthma.

          -  Any clinically significant and uncontrolled disease, including but not limited to the
             following: neurological, psychiatric, renal, immunological, endocrine/metabolic
             (including uncontrolled diabetes, hypokalemia or thyroid disease), cardiovascular,
             neuromuscular, hepatic, gastric, or hematological abnormalities, or peripheral
             vascular disease. Significant is defined as any disease that, in the opinion of the
             investigator, would put the safety of the subject at risk through study participation
             or would affect the efficacy analysis if the disease/condition exacerbated during the
             study.

          -  A respiratory diagnosis other than COPD (e.g., lung cancer, bronchiectasis,
             sarcoidosis, tuberculosis, lung fibrosis), including subjects with a diagnosis of
             alpha-1-antitrypsin deficiency. Allergic rhinitis is not exclusionary.

          -  An abnormal and clinically significant chest x-ray or computed tomography (CT) scan
             not believed to be due to the presence of COPD. A chest x-ray must be taken if the
             subject has not had one within 6 months of Visit 1.

          -  An abnormal and clinically significant 12-lead electrocardiogram (ECG). For the
             purposes of this study, an abnormal ECG is defined as a 12-lead tracing which is
             interpreted with (but not limited to) any of the following:

               -  Myocardial ischemia

               -  Clinically significant conduction abnormalities (e.g., left bundle branch block,
                  Wolff-Parkinson-White syndrome)

               -  Clinically significant arrhythmias (e.g., atrial fibrillation, ventricular
                  tachycardia) The study investigator will determine the clinical significance of
                  any ECG abnormality and determine if a subject is precluded from entering the
                  study.

          -  Previously diagnosed cancer unless it is in complete clinical remission (no evidence
             of any tumor burden) at Visit 1. Localized carcinomas of the skin that have been
             resected for cure are not considered exclusionary.

          -  Any immediate or delayed hypersensitivity to any beta-agonist, sympathomimetic drug,
             or intranasal, inhaled, or oral corticosteroid including any components of the
             formulations (e.g. lactose or milk protein).

          -  Initiation of systemic beta-blocker medications within 30 days of Visit 1.

          -  Use of products containing the protease inhibitor ritonavir (Norvir, Kaletra).

          -  Use of the following medications within the defined times prior to Visit 1:

        Medication (Exclusion Prior to Visit 1) Short-acting beta-agonists (e.g., albuterol) (6
        hours) Ipratropium (6 hours) Ipratropium/albuterol combination product (6 hours) Oral
        beta-agonists (48 hours) Salmeterol and formoterol (48 hours) Theophylline preparations (48
        hours) Tiotropium (48 hours) Long-acting beta-agonist/inhaled corticosteroid combination
        products (e.g., ADVAIR™ or Symbicort) (30 days) Inhaled corticosteroids (30 days) Oral or
        parenteral corticosteroids (30 days) Any investigational drug (30 days)

          -  Lung resection surgery (e.g., lung volume reduction surgery, or lobectomy) within 1
             year of Visit 1.

          -  A COPD exacerbation and/or infection of the upper or lower respiratory tract requiring
             treatment with systemic (oral or parenteral) corticosteroids and/or antibiotics that
             has not resolved within 30 days of Visit 1

          -  A COPD exacerbation that resulted in hospitalization that has not resolved within 3
             months of Visit 1.

          -  Use of nocturnal positive pressure [e.g., continuous positive airway pressure or
             bi-level positive airway pressure].

          -  A body mass index (BMI) of ≥ 40kg/m².

          -  Subject is a study investigator, sub-investigator, study coordinator, or employee of a
             participating investigator or immediate family members of the aforementioned.

          -  Any intellectual deficiency including illiteracy, history of substance abuse in the
             two years prior to Visit 1 (including drug and alcohol), or other conditions, which
             will limit the validity of informed consent to participate in the study.

          -  Supplemental oxygen, with the following exceptions:

               -  Use at high altitude (> 5000 feet) provided subject does not require a flow rate
                  of > 2 L/minute

               -  Use for exertion provided subject does not require > 2 hours per day of oxygen
                  and does not require a flow rate of > 2L/minute

               -  Use for nocturnal therapy provided subject does not require a flow rate of >
                  2L/minute