Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, obstructive lung diseases, Tiotropium
Brief summary
The purpose of this study is to evaluate the safety and efficacy of inhaled PT001 compared to placebo and tiotropium in patients with mild to moderate chronic obstructive pulmonary disease (COPD).
Interventions
DRUGInhaled PT001
single dose, inhaled
DRUGInhaled Placebo
single dose, inhaled
DRUGTiotropium Handihaler
single dose, tiotropium 18 mcg administered via the Handihaler
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * 40 - 75 years of age * Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods * COPD diagnosis * Current/former smokers with at least a 10 pack-year history of cigarette smoking * Patients with established clinical history of COPD and severity defined as a post-ipratropium FEV1/FVC ratio of ≤0.70 and FEV1 ≥50 and ≤85% of predicted normal at Screening * Must demonstrate reversibility to ipratropium demonstrated by a \>200 mL improvement over baseline and/or \>12% and \>150 mL improvement over baseline * Patients willing to stay at study site for at least 24 hours on each test day
Exclusion criteria
* Women who are pregnant or lactating * Primary diagnosis of asthma * Alpha-1 antitrypsin deficiency as the cause of COPD * Active pulmonary diseases * Prior lung volume reduction surgery * Abnormal chest X-ray (or CT scan) not due to the presence of COPD * Hospitalized due to poorly controlled COPD within 24 weeks of Screening * Unable to perform acceptable spirometry * Poorly controlled COPD in prior 6-weeks, defined as the occurrence of acute worsening of COPD requiring corticosteroids or antibiotics or acute worsening of COPD requiring treatment prescribed by a physician * Clinically significant medical conditions * Symptomatic prostatic hypertrophy or bladder neck obstruction * Known narrow-angle glaucoma * Lower respiratory tract infection requiring antibiotics in past 6 weeks * Clinically significant abnormal ECG * Clinically significant uncontrolled hypertension * Positive Hepatitis B surface antigen or Hepatitis C antibody * Cancer that has not been in complete remission for at least 5 years * History of hypersensitivity to any beta2-agonists or anticholinergics * History of severe milk protein allergy * Known or suspected history of alcohol or drug abuse * Medically unable to withhold short acting bronchodilators for 6-hours * Use of the medications below in specified time interval prior to Screening: 3 months: depot corticosteroids, intra-articular corticosteroids; 6 weeks: oral corticosteroids, antibiotics administered for a COPD exacerbation; and 1 month: P-glycoprotein inhibitors, CYP450 3A4 inhibitors, ICS \>1000 μg/day of fluticasone propionate or equivalent * The following COPD medications need to be stopped and switched to appropriate replacement therapies: tiotropium, oral beta2 agonists, LABAs, combination corticosteroid/LABAs, theophylline, leukotriene inhibitors,cromoglycate and nedocromil * Use of the following medications is prohibited: tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, beta-adrenergic antagonists, anticonvulsants (barbiturates, hydantoins, and carbamazepine and phenothiazines * Receiving long-term-oxygen or nocturnal oxygen therapy for \>12 hours a day * Diagnosis of sleep apnea that is uncontrolled * Participation in acute phase of pulmonary rehabilitation in prior 4 weeks * Will enter acute phase of pulmonary rehabilitation program during study * Unable to comply with study procedures * Affiliated with Investigator site * Questionable validity of consent * Use of investigational study drug/participation in clinical study in the last 30 days or 5 half lives prior to Screening, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak improvement in forced expiratory volume in one second (FEV1) | Day 1 | Day 1 serial FEV1 measured over 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to peak FEV1 | Day 1 | Day 1 serial FEV1 measured over 24 hours |
| FEV1 area under the curve (AUC) from 0 to 24 hours | Day 1 | Day 1 serial FEV1 measured over 24 hours |
| Time to onset of action (>10% improvement in FEV1 from baseline) | Day 1 | Day 1 serial FEV1 measured over 24 hours |
| Trough FEV1 at 12 and 24 hours | Day 1 | Day 1 serial FEV1 measured over 24 hours |
| Peak Improvement in inspiratory capacity (IC) | Day 1 | Day 1 serial IC measured over 24 hours |
| FEV1 AUC from 0 to 12 hours | Day 1 | Day 1 serial FEV1 measured over 24 hours |
Countries
United States
Outcome results
None listed