Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD
Condition: COPD
Intervention: Glycopyrronium; Tiotropium; Placebo to glycopyrronium; Placebo to tiotropium
Intervention description: Glycopyrronium capsule for inhalation once per day via SDDPI; Tiotropium capsule for inhalation once per day via HandiHaler® device; Placebo to glycopyrronium capsule for inhalation once per day via SDDPI; Placebo to tiotropium capsule for inhalation once per day via HandiHaler® device
Intervention MeSH terms: Glycopyrrolate; Tiotropium Bromide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 124.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: COPD, early morning symptoms

Summary:

      This study purpose is to further study the profiles of glycopyrronium (NVA237) and tiotropium
      during the first hours after dosing and their impact on pulmonary function, COPD symptoms and
      ability to perform daily activities by the patient.
    

Eligibility criteria:

        Inclusion criteria:

          -  Male and female adults aged ≥ 40 years.

          -  Co-operative outpatients with a clinical diagnosis of moderate to severe COPD
             confirmed by spirometry according to GOLD criteria 2013 and including all of the
             following: a) Current or ex-smokers who have a smoking history of at least 10 pack
             years (e.g.10 pack years = 1 pack /day x 10 years or ½ pack/day x 20 years). An
             ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at Screening.
             b) Patients with airflow limitation indicated by a post-bronchodilator FEV1 < 80% and
             ≥ 40% of the predicted normal value at Visit 2 (Post- bronchodilator refers to within
             10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol). c) .Post-bronchodilator
             FEV1/FVC < 0.7 at Visit 2 (Post- bronchodilator refers to within 10-15 min of
             inhalation of 400 µg (4x100 µg) of salbutamol).

          -  Patients with a COPD Assessment Test (CAT) score ≥ 10 at Visit 2.

        Exclusion criteria:

          -  Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid
             treatment or antibiotics and/or hospitalization in the 6 weeks prior to Visit 1. In
             the event of an exacerbation occurring during the Screening period (Visits 1-2), the
             patient must be discontinued from the study. The patient may be re-enrolled once the
             inclusion/exclusion criteria are met. Only one re-enrollment is allowed.

          -  Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1.
             Patients who develop a respiratory tract infection between Visit 1 and Visit 2 must
             discontinue from the trial, but may be permitted to re-enrol at a later date once the
             inclusion/exclusion criteria have been met. Only one re-enrollment is allowed.

          -  Patients on any long-acting bronchodilator therapy. Those patients may enter the study
             after bronchodilator withdrawal during a 10-day wash-out period (only rescue
             salbutamol allowed as bronchodilator therapy during wash-out). Patients on fixed
             combination of long acting β2-agonists/inhaled corticosteroid (LABA/ICS) therapy
             before screening must be switched to the equivalent dose of ICS monotherapy and
             salbutamol as rescue.

          -  Patients receiving any other prohibited COPD-related medications specified in Table
             5-1 must undergo the required wash-out period prior to Visit 2.

          -  Patients who have had a clinical history of asthma.

          -  Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis or clinically
             significant bronchiectasis.

          -  Patients with alpha-1-antitrypsin deficiency.

          -  Patients with contraindications for LAMA treatment including medical history of
             symptomatic prostatic hypertrophy, bladder neck obstruction, narrow-angle glaucoma and
             severe renal impairment (estimated glomerular filtration rate below 30 ml/min/1.73 m2)
             documented in the previous 6 months.

          -  Patients with a history of unstable cardiovascular disease or arrhythmias including
             atrial fibrillation/flutter or long QT syndrome or whose resting QTcF (calculated
             according to Fridericia QT correction formula preferred, but Bazett acceptable) is
             prolonged (≥ 450 msec for males and ≥ 460 msec for females) at screening (Visit 1) or
             baseline (Visit 2, baseline 1).

          -  Concomitant use of agents known to prolong the QT interval unless it can be
             permanently discontinued for the duration of study.

          -  Patients contraindicated for treatment with, or having a history of reactions/
             hypersensitivity to any of the following inhaled drugs, drugs of a similar class or
             any component thereof: -anticholinergic agents - long and short acting 2 agonists
             -sympathomimetic amines -excipients of the trial medication (lactose monohydrate
             and/or magnesium estearate)

          -  Patients whose body mass index (BMI) is less than 15 or greater than 40 kg/m2.

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases.

        Other exclusion criteria may apply