A Study to Assess the Efficacy of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration
Intervention: FF/VI 100/25 Inhalation Powder NDPI; Fluticasone Propionate/Salmeterol 250/50 Inhalation Powder ACCUHALER/DISKUS; Placebo Inhalation Powder NDPI; Placebo Inhalation Powder ACCUHALER/DISKUS; Salbutamol as needed
Intervention description: Subjects randomized to the FF/VI Inhalation Powder Novel Dry Powder Inhaler (NDPI) arm will receive a single inhalation of 100 mcg FF and 25 mcg VI via NDPI every morning for 12 weeks.; Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of 250 mcg Fluticasone Propionate and 50 mcg Salmeterol via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.; Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of placebo inhalation powder via NDPI every morning for 12 weeks.; Subjects randomized to the FF/VI Inhalation Powder NDPI arm will receive a single inhalation of placebo inhalation powder via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.; Salbutamol inhalation powder
Intervention MeSH terms: Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 828.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Vilanterol (VI); Novel Dry Powder Inhaler (NDPI); FEV1; Fluticasone Furoate (FF); COPD

Summary:

      This will be a Phase IIIb multicentre, randomized, double-blind, double-dummy, 12-week
      parallel group study evaluating the effects of once daily in the morning treatment of FF/VI
      Inhalation Powder versus Fluticasone Propionate/Salmeterol Inhalation Powder twice daily on
      lung function in COPD subjects.

      Subjects will be screened and will enter a 2-week, single-blind (placebo), Run-In Period to
      evaluate the subject's adherence with study treatment, study procedures and assessment of
      disease stability.

      At the end of the Run-In Period, subjects will return to the Clinic and who meet all of the
      Randomization Criteria will be randomized to double-blind study medication (12-week treatment
      period). Subjects will be randomized to receive either FF/VI 100/25 via NDPI or Fluticasone
      Propionate/Salmeterol 250/50mcg via ACCUHALER/DISKUS. Matching placebos will be available in
      NDPI and ACCUHALER/DISKUS. Each morning (approximately 6-10 AM) subjects will take 1
      inhalation from the NDPI followed by 1 inhalation from the ACCUHALER/DISKUS. Each evening
      (approximately 6-10 PM), approximately 12 hours after the morning dose with blinded study
      medication, subjects will take 1 inhalation from the ACCUHALER/DISKUS. Subjects will return
      to the clinic at the end of the treatment period.

      A follow-up phone contact will be performed approximately 7 days after the last clinic visit.
      The overall study duration (Screening to Follow-up) for each subject is approximately 15
      weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A male or female >=40 years of age at Screening (Visit 1).

          -  Capable of giving written informed consent.

          -  Female subjects must be post-menopausal or using a highly effective method for
             avoidance of pregnancy.

          -  Subjects with a clinical history of COPD in accordance with the following definition
             by the American Thoracic Society/European Respiratory Society.

          -  Subject with a measured post-albuterol (salbutamol) FEV1/forced vital capacity(FVC)
             ratio of <=0.70 at Screening.

          -  Subjects with a measured post-albuterol (salbutamol) FEV1 <=70% of predicted normal
             values.

          -  Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at
             Screening.

        Exclusion Criteria:

          -  Current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if
             they have a current diagnosis of COPD).

          -  Other respiratory disorders (alpha1-antitrypsin deficiency as the underlying cause of
             COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary
             fibrosis, pulmonary hypertension, interstitial lung diseases, or other active
             pulmonary diseases).

          -  Lung volume reduction surgery within the 12 months prior to Screening.

          -  Hospitalized due to poorly controlled COPD within 12 weeks of Screening.

          -  Poorly controlled COPD (occurrence of the following in the 6 weeks prior to Screening
             -Acute worsening of COPD that is managed by the subject with corticosteroids or
             antibiotics or that requires treatment prescribed by a physician).

          -  Lower respiratory tract infection that required the use of antibiotics within 6 weeks
             prior to Screening.

          -  Moderate/severe COPD exacerbation/lower respiratory tract infection during Run-In
             Period.

          -  Abnormal and clinically significant 12-lead ECG at Screening

          -  Historical or current evidence of uncontrolled or clinically significant disease like
             cardiovascular, hypertension, neurological, psychiatric, renal, hepatic,
             immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic
             ulcer disease, or haematological abnormalities. Significant is defined as any disease
             that, in the opinion of the investigator, would put the safety of the subject at risk
             through participation, or which would affect the efficacy or safety analysis if the
             disease/condition exacerbated during the study.

          -  History of hypersensitivity to any of the study medications or components of the
             inhalation powder; or history of severe milk protein allergy.

          -  Known or suspected history of alcohol or drug abuse within the last 2 years.

          -  Subjects who are medically unable to withhold their albuterol (salbutamol) and/or
             their ipratropium for the 4-hour period required prior to spirometry testing at each
             study visit.

          -  The subject has taken any other investigational drug within 30 days or 5 half-lives of
             the investigational product (IP) prior to the first dosing day in the current study.

          -  Use of additional medications prior to Screening (list of medications and time
             intervals are different for different class of medications and are indicated in the
             protocol)

          -  Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen
             therapy required for greater than 12 hours a day. Oxygen prn use (i.e., <=12 hours per
             day) is not exclusionary.

          -  Subjects who have participated in the acute phase of a Pulmonary Rehabilitation
             Program within 4 weeks prior to Screening

          -  Subjects at risk of non-compliance, or unable to comply with study procedures.

          -  Study investigators, sub-investigators, study coordinators, employees of a
             participating investigator or immediate family members of the aforementioned are
             excluded from participating in this study.

          -  Women who are pregnant or lactating or are planning on becoming pregnant during the
             study.

          -  Previously randomized to either the HZC113109 or HZC112352 clinical studies.