Study to Evaluate the Efficacy, Safety and Pharmacokinetics of PT001, PT003, and PT005 Following Chronic Dosing (7 Days) in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
Drug: PT003 MDI
Drug: Placebo MDI
Drug: PT001 MDI
Drug: PT005 MDI
Drug: Tiotropium bromide 18 μg (Spiriva Handihaler®)

Registration Number: NCT01085045

Lead Sponsor: Pearl Therapeutics, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 118

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

Other protocol defined inclusion/exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Formoterol Fumarate 12 μg (Foradil® Aerolizer®)	Formoterol Fumarate 12 μg (Foradil® Aerolizer®)	Formoterol fumarate inhalation powder 12 μg
Inhaled PT003 (Dose 1)	PT003 MDI	PT003 MDI Dose 1
Inhaled Placebo	Placebo MDI	Placebo MDI
Inhaled PT001 (Dose 1)	PT001 MDI	PT001 MDI Dose 1
Inhaled PT005 (Dose 2)	PT005 MDI	PT005 MDI Dose 2
Inhaled PT003 (Dose 2)	PT003 MDI	PT003 MDI Dose 2
Inhaled PT005 (Dose 1)	PT005 MDI	PT005 MDI Dose 1
Tiotropium bromide 18 μg (Spiriva Handihaler®)	Tiotropium bromide 18 μg (Spiriva Handihaler®)	Tiotropium Bromide inhalation powder

Primary Outcome Measures

Name	Time	Method
FEV1 AUC 0-12 on Day 7	"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 Outcome Measures

Name	Time	Method
Peak Change From BL in FEV1 on Day 7	Day 7	Peak change from Baseline (BL) in FEV1 on Day 7
Peak Change From BL in Inspiratory Capacity on Day 1	Day 1	Peak change from Baseline in Inspiratory Capacity (IC) on Day 1
12 hr Post-dose Trough FEV1 on Day 7	Day 7	12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7
Peak Change From BL in FEV1 on Day 1	Day 1	Peak change from Baseline in FEV1 on Day 1
Peak Change From BL IC on Day 7	Day 7	Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration
Change in Morning Pre-dose FEV1 on Day 7	Day 7	Change from Baseline in morning pre-dose FEV1 on Day 7
Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7
Time to Onset of Action >=10% Improvement in FEV1 on Day 1	Day 1	Time to Onset of Action where the improvement in FEV1 on Day 1 was \>=10%
Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1	Day 1	Time to Onset of Action where the improvement in FEV1 on Day 1 was \>= 12%
Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7
Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7
Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7

Trial Locations

Locations (14): Clinical Research Institute of Southern Oregon, PC
🇺🇸
Medford, Oregon, United States
Spartanburg Medical Research
🇺🇸
Spartanburg, South Carolina, United States
Respiratory Research Foundation - Burnside War Memorial Hospital
🇦🇺
Adelaide, South Australia, Australia
Clinical Research of West Florida, Inc.
🇺🇸
Clearwater, Florida, United States
American Health Research
🇺🇸
Charlotte, North Carolina, United States
Woolcock
🇦🇺
Glebe, New South Wales, Australia
Austrials
🇦🇺
Auchenflower, Queensland, Australia
Q-Pharm
🇦🇺
Herston, Queensland, Australia
Greenlane Clinical Centre
🇳🇿
Epsom, Auckland, New Zealand
NZ Respiratory & Sleep Institute
🇳🇿
Greenlane East, Auckland, New Zealand
Waikato Hospital
🇳🇿
Hamilton, Waikato, New Zealand
P3 Research
🇳🇿
Crofton Downs, Wellington, New Zealand
Lung Institute of WA
🇦🇺
Nedlands, Western Australia, Australia
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia