| Eligibility |
Inclusion Criteria:
- Males and nonpregnant females, ages 40 to 80 years old, inclusive.
- On a stable COPD medication regimen defined as: no new medications for or changes to
medications (dose/frequency) used to manage COPD within 60 days of screening.
- Willing and able to give informed consent and follow all study procedures and
requirements.
- Body mass index <35.
- Female subjects of child-bearing potential1 who are non-lactating, are using and agree
tocontinue using an acceptable method of contraception for at least 4 weeks prior to
first dose of study drug and until 12 weeks after last dose, and have a negative serum
pregnancy test during screening. Adequate contraception is defined as a contraceptive
method with a failure rate of less than 1% per year when used consistently and
correctly and when applicable, in accordance with the product label, for example:
abstinence from penile-vaginal intercourse; oral contraceptives, either combined or
progestogen alone; injectable progestogen; implants of etonogestrel or levonorgestrel;
estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or
intrauterine system; male partner sterilization at least 6 months prior to the female
subject's screening visit, and this male is the sole partner for that subject (the
information on the male partner's sterility can come from the site personnel's review
of the subject's medical records or interview with the subject on her medical
history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or
suppository); male condom combined with a female diaphragm, either with or without a
vaginal spermicide (foam, gel, film, cream, or suppository).
- Female subjects of childbearing potential who agree not to donate an ova during the
study and for at least 30 days after the last dose of study drug.
- If male, agrees to use a condom with spermicide (note: no restrictions are required
for a vasectomized male provided that his vasectomy was = 4 months prior to the
Screening Visit).
- Diagnosis of COPD, as defined by American Thoracic Society Global Initiative for
Chronic Obstructive Lung Disease criteria
- Post-bronchodilator FEV1 =30% and =79%
- Post-bronchodilator FEV1/FVC ratio =70%
- Current or former smoker with a history of = 10 pack-year history
Exclusion Criteria:
- Any condition that, in the opinion of the investigator, would interfere with the
subject'sability to complete the study, would interfere with the interpretation of
safety or efficacy, or would present an undue risk to the subject. In cases of
uncertainty, the investigator may contact the medical monitor for clarification.
- Known respiratory disorders other than COPD that, in the opinion of the investigator,
may present an unacceptable safety risk to a subject's study participation or could
confound the interpretation of the study safety or efficacy results. Examples include,
but are not limited to: alpha-1 antitrypsin deficiency, cystic fibrosis, significant
asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension,
pulmonary edema, or interstitial lung disease.
- Currently taking a non-selective beta blocker. Subjects who have been on a stable dose
of a cardioselective beta blocker for at least 3 months prior to screening are not
excluded (examples of cardioselective beta blockers are: metoprolol, atenolol,
bisoprolol, and nebivolol). Topical beta blockers for ophthalmologic conditions are
permitted.
- Uncontrolled diabetes defined as HbA1c > 8.0%.
- Renal impairment defined as estimated glomerular filtration rate <50 ml/min/1.73 m2 as
calculated by the Chronic Kidney Disease Epidemiology Collaboration equation.
- Liver disease as defined as one or more of the following:
1. AST or ALT > 2 times the upper limit of normal (ULN).
2. Total bilirubin > 2 times the ULN (subjects with bilirubin elevation patterns
consistent with Gilbert's disease are permitted).
3. A history of or suspected, in the opinion of the investigator, bleeding disorder.
Subjectson therapeutic anticoagulation are not excluded if the investigator
believes they are appropriately anticoagulated.
- Eosinophil count >600/mm3.
- History of a malignancy of any organ system (other than localized squamous or basal
cell carcinoma of the skin) treated or untreated within the last 2 years prior to
screening.
- Evidence or history of a clinically significant disease or abnormality, which, in the
opinion of the investigator, would present and unacceptable safety risk to a subject's
study participation or could confound the interpretation of the study efficacy or
safety results. Examples of these conditions include, but are not limited to: NYHA
Class II or higher congestive heart failure, uncontrolled hypertension, uncontrolled
coronary artery disease, thyrotoxicosis, stroke, or cardiac dysrhythmia.
- Conditions which, in the opinion of the investigator, may contraindicate the use of an
anticholinergic agent. Examples of these conditions may include, but are not limited
to: paradoxical bronchospasm, narrow-angle glaucoma, prostatic hyperplasia, bladder
neck obstruction, chronic constipation, or altered gastrointestinal motility.
- History of myasthenia gravis.
- Use of oral corticosteroids or oral antibiotics within 6 weeks prior to the Screening
Visit.
- Subjects who have a positive test result on the screening urine drug screen for banned
substances, including tetrahydrocannabinol or controlled substance(s) for which the
subject does not have a valid prescription. Subjects taking cannabidiol should also be
excluded.
- History of allergy or hypersensitivity to anticholinergic/muscarinic receptor
antagonist agents, beta-2 adrenergic agonists, lactose/milk proteins, or specific
intolerance to aerosolized tiotropium-containing products or known hypersensitivity to
any of the proposed ingredients or components of the delivery system.
- Hospitalization for COPD or pneumonia within 8 weeks of study enrollment.
- Treatment for COPD exacerbation (defined as change in COPD symptoms requiring
antibiotics and/or corticosteroids) within 12 weeks prior to enrollment.
- Have participated in pulmonary rehabilitation within 90 days of screening or are
planning to participate in pulmonary rehabilitation during the course of the study
- History of 3 or more COPD exacerbations within 12 months prior to enrollment.
- Inability to refrain from COPD medications as prohibited by study protocol.
- Requires any supplemental oxygen therapy (including nocturnal oxygen).
- Acute (viral or bacterial) upper or lower respiratory tract infection, sinusitis,
rhinitis, pharyngitis, urinary tract infection or illness within 6 weeks prior to
enrollment.
- Abnormal and clinically significant electrocardiogram (ECG) findings, as determined by
the investigator, at screening or during treatment.
- Lung volume reduction surgery within 12 months prior to the initiation of the study.
- Have an oxygen saturation <91% on room air at screening measured by pulse oximetry.
- Have participated in an investigational drug study within 30 days prior to screening.
In addition, it is necessary that at least 5 half-lives of the previously administered
investigational drug have elapsed by Visit 1.
- Subjects currently infected with COVID-19 or subjects who have previously been
infected and have residual symptoms that, in the opinion of the investigator, would
present a safety risk to study participation or could potentially interfere with the
interpretation of safety or efficacy data in the current study. COVID-19 infection is
defined as laboratory evidence of COVID-19 infection or by a constellation of
signs/symptoms that, in the opinion of the investigator, are/were consistent with
COVID-19 infection. Note: COVID-19 vaccination is not exclusionary.
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