Assessment of the Safety and Ability of a Once-a-day Dose of an Orally Inhaled Medicine [ie, Glycopyrrolate Inhalation Solution = GIS] to Improve Airflow in the Lungs When Delivered With an Electronic eFlow Nebulizer System in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Glycopyrrolate Inhalation Solution 25mg; Glycopyrrolate Inhalation Solution 75mg; Glycopyrrolate Inhalation Solution 200mg; Glycopyrrolate Inhalation Solution 200mg Jet; Glycopyrrolate Inhalation Solution 500mg; Glycopyrrolate Inhalation Solution1000mg; Placebo
Intervention description: 25 μg oral inhalation via eFlow Nebulizer, once daily; 75 μg oral inhalation via eFlow Nebulizer, once daily; 200 μg oral inhalation via eFlow Nebulizer, once daily; 200 μg oral inhalation via inhalation via jet nebulizer, once daily; 500 μg oral inhalation via eFlow nebulizer, once daily; 1000 μg oral inhalation via eFlow nebulizer, once daily; Placebo 0.5 mL oral inhalation via jet nebulizer, once daily
Intervention MeSH terms: Glycopyrrolate; Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Emphysema; Chronic bronchitis; COPD; Chronic Obstructive Pulmonary Disease

Summary:

      The study assessed the safety and ability of several doses of an orally inhaled medicine [ie,
      Glycopyrrolate Inhalation Solution = GIS] to improve airflow in the lungs when delivered with
      an electronic eFlow nebulizer system in patients with Chronic Obstructive Pulmonary Disease
      (COPD). The study was conducted in 12 patients in 2 parts. Part 1 was designed to find the
      once-a- day GIS dose that produced the highest improvement in lung airflow. Part 2 tested the
      GIS dose with the highest improvement in lung airflow and a placebo (ie, no drug) delivered
      by a general purpose nebulizer. The airflow improvements of the same GIS dose were compared
      between the two nebulizer systems to determine what effect the device had on GIS delivery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female patients aged 40 through 75 years, inclusive

          2. A clinical diagnosis of COPD according to the GOLD guidelines

          3. Current smokers or ex-smokers with at least 10 pack-year smoking history (e.g., at
             least 1 pack/day for 10 years, or 10 packs/day for 1 year)

          4. Post-bronchodilator FEV1 40-80% of predicted normal

          5. Post-bronchodilator FEV1/FVC ratio < 0.70

          6. Improvement in FEV1 >12% (minimum 150 mL) following inhalation of ipratropium bromide

          7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines

          8. If female and of childbearing potential, must have had a negative pregnancy test and
             was not lactating at the Screening Visit, and was using one of the following
             acceptable means of birth control throughout the study:

               -  Post-menopausal for at least two years

               -  Surgically sterile

               -  Oral contraceptives (taken for at least one month prior to the Screening Visit)

               -  Approved implantable or injectable contraceptives (e.g., Norplant®, Depo-Provera®
                  or equivalent)

               -  Barrier methods (e.g., condoms with spermicide)

               -  Intrauterine device (i.e., IUD)

               -  Vasectomy of male partner

               -  Non-heterosexual life style

          9. Willing and able to provide written informed consent

        Exclusion Criteria:

          1. Current evidence or recent history of any clinically significant disease (other than
             COPD) or abnormality in the opinion of the Investigator that would put the patients at
             risk or which would compromise the quality of the study data; including but not
             limited to cardiovascular disease, myocardial infraction, hypertension, arrhythmia,
             diabetes, neurological or neuromuscular disease, liver disease, gastrointestinal
             disease or electrolyte abnormalities.

          2. Recent history of an exacerbation of airway disease within 3 months or need for
             increased treatments for COPD within 6 weeks prior to the Screening Visit.

          3. Regular use of daily oxygen therapy.

          4. Use of systemic (e.g., intramuscular or intravenous) steroids within 3 months prior to
             the Screening Visit

          5. Respiratory tract infection within 6 weeks prior to the Screening Visit

          6. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease

          7. History of urinary retention or bladder neck obstruction type symptoms

          8. History of narrow-angle glaucoma

          9. Current or recent history (previous 12 months) of excessive use or abuse of alcohol

         10. Current evidence or history of abusing legal drugs or the use of illegal drugs or
             substances

         11. History of hypersensitivity or intolerance to aerosol medications

         12. Participation in another investigational drug study where drug was received within 30
             days prior to the Screening Visit