PT001 MDI Versus Atrovent Study in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Phase 2

Completed

Interventions: Drug: PT001 MDI
Drug: Ipratropium Bromide HFA Inhalation Aerosol
Other: Placebo MDI

Brief Summary: The overall objective of this study is to determine an optimal dose and dosing regimen of PT001 MDI for further evaluation in later stage studies.

Detailed Description: The primary objective of this study is to demonstrate efficacy relative to placebo of PT001 MDI in patients with moderate to severe chronic obstructive pulmonary disease (COPD) within the range of doses evaluated in this protocol. To this end, each dose of PT001 MDI will be compared to placebo with respect to the primary efficacy endpoint, FEV1 AUC0-12 relative to baseline.

Recruitment & Eligibility

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

Key

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

Other inclusion/exclusion criteria as defined in the protocol

Arm && Interventions

Group	Intervention	Description
PT001 MDI (Dose 3)	PT001 MDI	PT001 MDI
PT001 MDI (Dose 4)	PT001 MDI	PT001 MDI
PT001 MDI (Dose 1)	PT001 MDI	PT001 MDI
Ipratropium Bromide HFA Inhalation Aerosol	Ipratropium Bromide HFA Inhalation Aerosol	Ipratropium Bromide HFA Inhalation Aerosol
PT001 MDI (Dose 2)	PT001 MDI	PT001 MDI
Placebo MDI	Placebo MDI	PT001 Placebo MDI

Primary Outcome Measures

Name	Time	Method
FEV1 AUC0-12	Day 7 ( -1 hour, -30 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 5.5 hours, 6.5 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours)	FEV1 AUC0-12 following chronic dosing (1 week), normalized.

Secondary Outcome Measures

Name	Time	Method
Peak Change From Baseline in FEV1 on Day 1	Day 1	Highest value of FEV1 post-dose minus baseline on Day 1 (baseline-adjusted)
Peak Change From Baseline in IC on Day 1	Day 1	Peak change from baseline in Inspiratory Capacity (IC) on Day 1 (mean of 1 and 2 hours post-dose minus baseline on Day 1)
Change From Baseline in Morning Pre-dose FEV1 on Day 7	Day 7	Change from baseline in morning pre-dose FEV1
Time to Onset of Action ( ≥10% Improvement in FEV1) on Day 1	Day 1 (15 min, 30 min, 1 hour, 2 hours)	Time to onset of action ( ≥10% improvement in FEV1)
Proportion of Subjects Achieving at Least 12% Improvement in FEV1 on Day 1	Day 1	Proportion of subjects achieving at least 12% improvement in FEV1 (relative to baseline)
Peak Change From Baseline in FEV1 on Day 7	Day 7	Peak change from baseline in FEV1
Change From Baseline in 12-hour Post-dose Trough FEV1 on Day 7	Day 7	Change from baseline in 12-hour post-dose trough FEV1
Peak Change From Baseline in IC on Day 7	Day 7	Peak change from baseline in IC