Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD)
Brief summary
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.
Detailed description
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.
Interventions
COMBINATION_PRODUCTGlyocopyrrolate Inhalation Solution administered by Magnair
glycopyrrolate Inhalation Solution 25mcg, single dose
DRUGPlacebo administered by Magnair
Placebo Inhalation Solution
Sponsors
Sunovion Respiratory Development Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A Randomized, Double-blind, Placebo-controlled, 2-Way Crossover Study
Eligibility
Sex/Gender
ALL
Age
40 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female and ≥ 40 years of age at Screening with a confirmed diagnosis of COPD. 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. *
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Residual Volume (RV) at 6 Hours Postdose | 6 hours post dose | Change from baseline in Residual Volume (Residual Volume is defined as the volume of gas that remains in lungs after maximal exhalation) at 6 hours postdose. |
Countries
United States
Participant flow
Pre-assignment details
There were 44 subjects enrolled in the study. There were 22 subjects that screen failed and did not participate in the study. There were 22 subjects that started the study.
Participants by arm
| Arm | Count |
|---|---|
| Glycopyrrolate Inhalation Solution (GIS) First, Then Placebo Inhalation Solution (PIS) Treatment sequence AB: Single dose of GIS 25 mcg (Treatment A) to matching PIS (Treatment B) | 11 |
| Placebo Inhalation Solution (PIS) First, Then Glycopyrrolate Inhalation Solution (GIS) Treatment sequence BA: Matching PIS (Treatment B) to single dose of GIS 25 mcg (Treatment A) | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | COVID-19: SUBJECT REFUSED STUDY VISITS DUE TO COVID-19 THREAT | 1 | 0 |
Baseline characteristics
| Characteristic | Glycopyrrolate Inhalation Solution (GIS) First, Then Placebo Inhalation Solution (PIS) | Placebo Inhalation Solution (PIS) First, Then Glycopyrrolate Inhalation Solution (GIS) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Continuous | 65.4 Years STANDARD_DEVIATION 8.03 | 66.5 Years STANDARD_DEVIATION 8.12 | 65.9 Years STANDARD_DEVIATION 7.9 |
| Baseline Residual Volume for GIS 25 mcg | 3.132 L STANDARD_DEVIATION 0.5631 | 3.696 L STANDARD_DEVIATION 0.757 | 3.414 L STANDARD_DEVIATION 0.7123 |
| Baseline Residual Volume for Placebo | 3.174 L STANDARD_DEVIATION 0.5669 | 3.592 L STANDARD_DEVIATION 0.6915 | 3.404 L STANDARD_DEVIATION 0.6575 |
| BMI (kg/m^2) | 34.67 kg/m^2 STANDARD_DEVIATION 6.131 | 30.14 kg/m^2 STANDARD_DEVIATION 7.086 | 32.4 kg/m^2 STANDARD_DEVIATION 6.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 166.4 cm STANDARD_DEVIATION 12.18 | 175.1 cm STANDARD_DEVIATION 8.94 | 170.8 cm STANDARD_DEVIATION 11.33 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
| Weight (kg) | 96.69 kg STANDARD_DEVIATION 22.683 | 92.65 kg STANDARD_DEVIATION 23.808 | 94.67 kg STANDARD_DEVIATION 22.785 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 0 / 20 | 1 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 22 |
Outcome results
Primary
Change From Baseline in Residual Volume (RV) at 6 Hours Postdose
Change from baseline in Residual Volume (Residual Volume is defined as the volume of gas that remains in lungs after maximal exhalation) at 6 hours postdose.
Time frame: 6 hours post dose
Population: Efficacy Population : all subjects who were randomized, received at least one dose of study treatment, and have a baseline and at least one post-baseline RV measurement within the same period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Residual Volume (RV) at 6 Hours Postdose | 0.004 L | Standard Error 0.1392 |
| GIS 25 mcg Single Dose | Change From Baseline in Residual Volume (RV) at 6 Hours Postdose | -0.319 L | Standard Error 0.1313 |
p-value: 0.098795% CI: [-0.711, 0.066]Mixed Models Analysis