Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD
Condition: COPD
Intervention: GFF MDI (PT003); Placebo MDI
Intervention description: Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI); Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 4.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a randomized, double-blind, placebo-controlled, single-center, chronic-dosing (7
      days), two-period, two-treatment, cross-over study to evaluate the treatment effect of PT003
      compared with that of Placebo MDI on Cardiovascular Hemodynamics following chronic-dosing (7
      days) in subjects with moderate to severe COPD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 40 years of age and no older than 80 at Visit 1.

          -  Women of non-child bearing potential,or negative serum pregnancy test at Screening,
             and agrees to acceptable contraceptive methods used consistently and correctly from
             Screening until 14 days after final visit

          -  Evidence of lung hyperinflation

          -  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.

          -  Pre- and Post-bronchodilator FEV1/FVC ratio must be <0.70

          -  Post-bronchodilator FEV1 must be ≥30% to <65% predicted normal value, calculated using
             NHANES III reference equations.

        Exclusion Criteria:

          -  Significant diseases or conditions other than COPD which, in the opinion of the
             Investigator, may put the patient at risk

          -  Women who are pregnant or lactating or are planning to become pregnant during the
             course of the study

          -  Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma
             or other active pulmonary disease

          -  Subjects who have been hospitalized due to poorly controlled COPD within 3 months
             prior to Screening

          -  Subjects who have 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

          -  Subjects who have clinically significant uncontrolled hypertension.

          -  Subjects with symptomatic prostatic hypertrophy that is clinically significant and not
             adequately controlled with appropriate therapy, in the opinion of the Investigator.

          -  Subjects with bladder neck obstruction or urinary retention that is clinically
             significant in the opinion of the Investigator.

          -  Subjects with a calculated creatinine clearance ≤30 mL/minute using Chronic Kidney
             Disease Epidemiology Collaboration. (CKD-EPI) formula at Screening and on repeat
             testing prior to Visit 2.

          -  Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥
             1.5 times upper limit of normal at Screening and on repeat testing prior to Visit 2

          -  Subjects who have cancer that has not been in complete remission for at least five
             years.

          -  Subjects with a diagnosis of glaucoma, who in the opinion of the Investigator, have
             not been adequately treated.

          -  Subjects with a clinically significant ECG

          -  Subjects who were previously enrolled in any previous PT001, PT003, or PT005 study
             conducted or sponsored by Pearl.