Assessment of the Safety and Ability of a Once-a-day Dose of an Orally Inhaled Medicine [i.e., Glycopyrrolate Inhalation Solution = GIS] to Improve Airflow in the Lungs When Delivered Using an eFlow Nebulizer 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 Solution12.5μg; Glycopyrrolate Inhalation Solution 50μg; Glycopyrrolate Inhalation Solution 100μg; Glycopyrrolate Inhalation Solution 200μg; Glycopyrrolate Inhalation Solution 400μg; Placebo 0.5mL
Intervention description: Glycopyrrolate Inhalation Solution12.5μg via eFlow, once daily; Glycopyrrolate Inhalation Solution 50μg via eFlow, once daily; Glycopyrrolate Inhalation Solution 100μg via eFlow, once daily; Glycopyrrolate Inhalation Solution 200μg via eFlow, once daily; Glycopyrrolate Inhalation Solution 400μg via eFlow, once daily; Placebo 0.5mL via eFlow, once daily
Intervention MeSH terms: Glycopyrrolate; Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 42.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; COPD; Emphysema; Chronic bronchitis

Summary:

      The study assessed the safety and ability of an orally inhaled medicine [i.e., Glycopyrrolate
      Inhalation Solution = GIS] to improve airflow in the lungs when delivered using an eFlow
      nebulizer in 42 patients with Chronic Obstructive Pulmonary Disease (COPD). Each patient
      randomly received several, single doses of GIS, or placebo, separated by approximately 1 to 2
      weeks. After the dose was given, lung airflow was measured over 24 hours and blood was
      collected to measure how much GIS was in the bloodstream. The study was conducted to find the
      once-a- day GIS dose that produced the highest improvement in lung airflow using the eFlow
      nebulizer.
    

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

          4. Post-bronchodilator FEV1 30-70% of predicted normal at the Screening Visit

          5. Post-bronchodilator FEV1/FVC ratio < 0.70 at the Screening Visit

          6. Improvement in FEV1 >12% and 150 mL following inhalation of ipratropium bromide at the
             Screening Visit

          7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines

          8. Willing to stay at the study site for approximately 30 hours on each treatment visit

          9. Willing and able to provide written informed consent

        Exclusion Criteria:

          1. Females who are pregnant or lactating at the Screening Visit, or if of childbearing
             potential not using one of the following acceptable means of birth control throughout
             the study:

               -  Abstinence

               -  Post-menopausal for at least two years

               -  Surgically sterile (i.e., tubal ligation, hysterectomy)

               -  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

          2. 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 subject at
             risk or which would compromise the quality of the study data; including but not
             limited to cardiovascular disease, myocardial infarction, cardiac failure,
             uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes,
             neurologic or neuromuscular disease, liver disease, gastrointestinal disease or
             electrolyte abnormalities

          3. Recent history of hospitalization due to an exacerbation of airway disease within 3
             months or need for increased treatments for COPD within 6 weeks prior to the Screening
             Visit

          4. Primary diagnosis of asthma

          5. Prior lung volume reduction surgery or history of chest/lung irradiation

          6. Regular use of daily oxygen therapy

          7. Use of systemic (eg, intramuscular or intravenous) steroids within 3 months prior to
             the Screening Visit

          8. Respiratory tract infection within 6 weeks prior to the Screening Visit

          9. History of tuberculosis, bronchiectasis or other non- specific pulmonary disease

         10. History of urinary retention or bladder neck obstruction type symptoms

         11. History of narrow-angle glaucoma

         12. Clinically significant abnormal ECG

         13. Positive Hepatitis B surface antigen or positive Hepatitis C antibody

         14. Positive screening test for HIV antibodies

         15. Current or recent history (previous 12 months) of excessive use or abuse of alcohol

         16. Current evidence or history of abusing legal drugs or use of illegal drugs or
             substances

         17. Donation of 450 mL of blood within 8 weeks of the Screening Visit

         18. History of hypersensitivity or intolerance to aerosol medications

         19. Participation in another investigational drug study was received within 30 days prior
             to the Screening Visit