A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (7 Days), Four-Period, Eight-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Two Doses of PT003, Two Doses of PT005 and One Dose of PT001 in Patients With Moderate to Very Severe COPD, Compared With Foradil® Aerolizer® (12 μg, Open-Label) and Spiriva® Handihaler® (18 μg, Open-Label) as Active Controls
Overview
- Phase
- Phase 2
- Intervention
- PT003 MDI
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- Pearl Therapeutics, Inc.
- Enrollment
- 118
- Locations
- 14
- Primary Endpoint
- FEV1 AUC 0-12 on Day 7
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to evaluate, after 1 week of dosing, the efficacy and safety of PT003 compared with its individual components (PT001 and PT005), placebo and two active comparators to demonstrate superiority of the combination to its components, and to assess the relative contribution of the components compared with placebo, in patients with moderate to very severe COPD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •40 - 80 years of age
- •Clinical history of COPD with airflow limitation that is not fully reversible
- •Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods
- •Current/former smokers with at least a 10 pack-year history of cigarette smoking
- •A measured post- bronchodilator FEV1/FVC ratio of \< or = 0.70
- •A measured post- bronchodilator FEV1 \> or = 750ml or 30% predicted and \< or = 80% of predicted normal values
- •Able to change COPD treatment as required by protocol
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 3 months of Screening
- •Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy)
- •Cancer that has not been in complete remission for at least 5 years
- •Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives
Arms & Interventions
Inhaled PT003 (Dose 1)
PT003 MDI Dose 1
Intervention: PT003 MDI
Inhaled PT003 (Dose 2)
PT003 MDI Dose 2
Intervention: PT003 MDI
Inhaled PT005 (Dose 1)
PT005 MDI Dose 1
Intervention: PT005 MDI
Inhaled PT005 (Dose 2)
PT005 MDI Dose 2
Intervention: PT005 MDI
Inhaled Placebo
Placebo MDI
Intervention: Placebo MDI
Tiotropium bromide 18 μg (Spiriva Handihaler®)
Tiotropium Bromide inhalation powder
Intervention: Tiotropium bromide 18 μg (Spiriva Handihaler®)
Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
Formoterol fumarate inhalation powder 12 μg
Intervention: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
Inhaled PT001 (Dose 1)
PT001 MDI Dose 1
Intervention: PT001 MDI
Outcomes
Primary Outcomes
FEV1 AUC 0-12 on Day 7
Time Frame: "Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration
Secondary Outcomes
- Peak Change From BL in FEV1 on Day 1(Day 1)
- Peak Change From BL in Inspiratory Capacity on Day 1(Day 1)
- 12 hr Post-dose Trough FEV1 on Day 7(Day 7)
- Peak Change From BL in FEV1 on Day 7(Day 7)
- Peak Change From BL IC on Day 7(Day 7)
- Change in Morning Pre-dose FEV1 on Day 7(Day 7)
- Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7(Day 7)
- Time to Onset of Action >=10% Improvement in FEV1 on Day 1(Day 1)
- Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1(Day 1)
- Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7(Day 7)
- Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7(Day 7)
- Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7(Day 7)