Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® (PINNACLE 3)
Condition: Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: GFF MDI (PT 003); GP MDI (PT001); FF MDI (PT005); Open-label tiotropium bromide inhalation (Spiriva® Handihaler®)
Intervention description: GFF MDI administered as two puffs 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)
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: 892.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a multi-center, randomized, double-blind, parallel group, chronic dosing,
      active-controlled, 28-week safety extension study of the two pivotal 24-week safety and
      efficacy studies (Studies PT003006 and PT003007). This study is designed to assess the
      long-term safety and tolerability of Glycopyrrolate (GP) and Formoterol Fumarate (FF)
      combination (GFF) metered dose inhaler (MDI), GP MDI, and FF MDI in subjects with moderate to
      very severe COPD over a total observation period of 52 weeks. Open-label Spiriva is included
      as an active control. To be eligible for this study, a subject must complete participation in
      Study PT003006 (NCT01854645) or Study PT003007 (NCT01854658).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Participant in/completion of previous 24-week PINNACLE Phase III Trial.

          -  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.

          -  Subjects with FEV1/forced vital capacity (FVC) ratio of <0.70 and FEV1 <80% predicted
             normal and ≥750 mL if FEV1 <30% of predicted normal value.

          -  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 electrocardiogram (ECG)

          -  Abnormal liver function tests defined as alanine transaminase (ALT), aspartate
             transaminanse (AST), 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