Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD); (PINNACLE 1)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: GFF MDI; GP MDI; FF MDI; Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®); Placebo MDI
Intervention description: GFF MDI administered as two puffs Bis in Di.e. Twice Daily (BID); GP MDI administered as two puffs BID; FF MDI administered as two puffs BID; Taken as 1 capsule daily containing 18 µg of open-label tiotropium via the Handihaler dry powder inhaler (DPI); Inhaled placebo administered as two puffs BID
Intervention MeSH terms: Bromides; Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2103.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The overall objective of this study is to assess the efficacy and safety of treatment with
      PT003 (GFF MDI), PT005 (FF MDI), PT001 (GP MDI), and open-label tiotropium bromide inhalation
      powder compared with each other and Placebo MDI over 24 weeks in subjects with moderate to
      very severe COPD.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Male or female subjects at least 40 years of age and no older than 80 at Visit 1.

          -  Subjects with an established clinical history of COPD as defined by the American
             Thoracic Society (ATS)/European Respiratory Society (ERS)

          -  Current or former smokers with a history of at least 10 pack-years of cigarette
             smoking.

          -  Average f the -60 and the -30 min pre-dose FEV1 assessments must be < 80% predicted
             normal value calculated using National Health and Nutrition Examination Survey
             (NHANES) III reference equations.

          -  Subjects willing and, in the opinion of the investigator, able to adjust current COPD
             therapy as required by the protocol

        Key Exclusion Criteria:

          -  Significant diseases other than COPD, i.e. disease or condition which, in the opinion
             of the investigator, may put the patient at risk because of participation in the study
             or may influence either the results of the study or the subject's ability to
             participate in the study

          -  Current diagnosis of asthma or alpha-1 antitrypsin deficiency

          -  Other active pulmonary disease such as active tuberculosis, lung cancer,
             bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary
             pulmonary hypertension, or uncontrolled sleep apnea

          -  Hospitalized due to poorly controlled COPD within 3 months prior to screening or
             during the Screening Period

          -  Poorly controlled COPD, defined as acute worsening of COPD that requires treatment
             with oral corticosteroids or antibiotics within 6 weeks prior to screening or during
             the Screening Period

          -  Lower respiratory tract infections that required antibiotics within 6 weeks prior to
             screening or during the Screening Period

          -  Unstable ischemic heart disease, left ventricular failure, or documented myocardial
             infarction within 12 months of enrollment.

          -  Recent history of acute coronary syndrome, percutaneous coronary intervention,
             coronary artery bypass graft within the past three months

          -  Congestive heart failure (CHF) New York Heart Association (NYHA) Class III/IV)

          -  Clinically significant abnormal 12-lead ECG

          -  Abnormal liver function tests defined as aspartate transaminase (AST), alanine
             transaminase (ALT), or total bilirubin ≥ 1.5 times upper limit of normal at Visit 1
             and on repeat testing

          -  Cancer not in complete remission for at least five years

          -  History of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic
             anticholinergics, lactose/milk protein or any component of the MDI

        Other protocol-defined inclusion/exclusion criteria may apply