A Randomized, Double-blind, Placebo-controlled, 2-Way Crossover Study of the Effect of a Single Dose of Glycopyrrolate Inhalation Solution (GIS) on Lung Hyperinflation in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
A Randomized, Double-blind, Placebo-controlled, 2-Way Crossover Study of the Effect of a Single Dose of Glycopyrrolate Inhalation Solution (GIS) on Lung Hyperinflation in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
A clinical study to investigate if a single dose of an approved drug product (glycopyrrolate Inhalation Solution) reduces trapped air in the lungs of participants with chronic obstructive pulmonary disease. This study is accepting male and female participants over the age of 40. The study will be conducted at one site located in the United States.
This is a single center, randomized, double-blind, placebo-controlled, single-dose, 2-way crossover study in approximately 20 adult subjects ≥ 40 years of age with COPD. The study is designed to evaluate the effect of a single dose of GIS on lung hyperinflation. The two study treatments, both administered using the Magnair device.
The study will randomize 10 subjects per treatment sequence, for a total of 20 subjects. At the Sponsor's discretion, additional subjects may be enrolled in an effort to achieve at least 20 completers, with no more than 24 subjects randomize.
The study will consist of a Screening period, a randomized 2-way cross-over treatment period during which subjects will receive two single-doses each separated by a 7-day washout period, and a follow-up 7 (± 2) days after the last study drug dose.
This study is designed to test the hypothesis that in adults with COPD subjects as characterized by the study inclusion/exclusion criteria, after 2 cross-over periods of treatment, the primary null hypothesis for this study is that the mean change of RV from baseline at 6 hours postdose for a single dose of GIS is equal to the mean change of RV from baseline at 6 hours postdose for a single dose of placebo inhalation solution (PIS). The alternative hypothesis is that these means are different.
Inclusion Criteria:
Subject must have the ability to comprehend the informed consent form and be willing to provide informed consent.
Subject must possess an educational level and degree of understanding of English that enables them to communicate suitably with the Investigator and the study coordinator.
Subject has a postbronchodilator (following inhalation of ipratropium bromide) FEV1 ≥ 30% and < 80% of predicted normal at Screening.
Subject has a postbronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio of < 0.70 at Screening.
Subject has a RV ≥ 130% predicted value at Screening (prior to reversibility testing) Subject is a current or former smoker with at least 10 pack-years of cigarette smoking history at Screening.
Subject has a score of ≥ 2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening.
Subject, if female of child bearing potential, must have a negative serum pregnancy test at Screening. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control: a) an oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 30 days prior to entering the study with continued use throughout the study and for thirty days following participation; b) barrier method of contraception, eg, condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence. A follicle stimulating hormone (FSH) test will be used to confirm menopause in postmenopausal females.
Subject is willing and able to attend all study visits and adhere to all study assessments and procedures.
Subject is female who is pregnant or lactating or are planning on becoming pregnant during the study.
Subject has a history of asthma. Subject has a blood eosinophil count > 5% of total white blood cell count. Subject has life-threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to Screening.
Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 12 weeks prior to Screening.
Use of daily oxygen therapy > 12 hours per day Subject is unable to perform plethysmography. Subject is unable to use the Magnair Nebulizer System. Subject has history of narrow angle glaucoma Subject has history of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months prior to screening.
subject has history of long QT syndrome. subject has a QTcF > 450 msec (males) or > 470 msec (females) at Screening, unless discussed with and approved by the Medical Monitor.
Subject has a cardiac implanted device (internal defibrillator, pacemaker). Current severe heart failure (New York Heart Association Class IV) [New York Heart Association, 1994].
Subject has history of malignancies within the past 5 years, with the exception of basal cell carcinoma.
Subject has known comorbidities including unstable cardiac, pulmonary, or psychiatric disease, or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject.
Subject has participated in another investigational drug study (within 30 days prior to Screening).
Subjects who are study site staff members or relatives of study site staff members.
Subjects with a history of allergic reaction to glycopyrrolate, tiotropium, albuterol, or any components of the study medications.
Subjects with a known allergy to hydrocolloid gel adhesive are excluded from wearing the VitalPatch Biosensor.
-Continuation Criteria Subject has not had an exacerbation of COPD. Subject completes the 7-day washout period and continues to withhold restricted medications.
In the opinion of the Investigator, the subject has not had any change that would put the safety of the subject at risk through participation.