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)

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: PT003 MDI; Drug: PT005 MDI; Drug: Placebo MDI; Drug: Tiotropium bromide 18 μg (Spiriva Handihaler®); Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®); Drug: PT001 MDI

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Caringbah, New South Wales, Australia, 2229
      • AusTrials
    • Glebe, New South Wales, Australia, 2037
      • Woolcock
    • Hornsby, New South Wales, Australia, 2077
      • AusTrials
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • AusTrials
    • Herston, Queensland, Australia, 4006
      • Q-Pharm
  • South Australia
    • Adelaide, South Australia, Australia
      • Respiratory Research Foundation - Burnside War Memorial Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6006
      • Lung Institute of WA
• New Zealand
  • Auckland
    • Epsom, Auckland, New Zealand, 1051
      • Greenlane Clinical Centre
    • Greenlane East, Auckland, New Zealand, 1051
      • NZ Respiratory & Sleep Institute
  • Waikato
    • Hamilton, Waikato, New Zealand, 3240
      • Waikato Hospital
  • Wellington
    • Crofton Downs, Wellington, New Zealand, 6143
      • P3 Research
• United States
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • American Health Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon, PC
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Formoterol Fumarate 12 μg (Foradil® Aerolizer®); Formoterol fumarate inhalation powder 12 μg	Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®); Inhaled formoterol fumarate 12 μg (Foradil® Aerolizer®) administered BID for 7 days
Experimental: Inhaled PT003 (Dose 1); PT003 MDI Dose 1	Drug: PT003 MDI; Inhaled PT003 MDI administered as two puffs BID for 7 days
Experimental: Inhaled PT003 (Dose 2); PT003 MDI Dose 2	Drug: PT003 MDI; Inhaled PT003 MDI administered as two puffs BID for 7 days
Experimental: Inhaled PT005 (Dose 1); PT005 MDI Dose 1	Drug: PT005 MDI; Inhaled PT005 MDI administered as two puffs BID for 7 days
Experimental: Inhaled PT005 (Dose 2); PT005 MDI Dose 2	Drug: PT005 MDI; Inhaled PT005 MDI administered as two puffs BID for 7 days
Placebo Comparator: Inhaled Placebo; Placebo MDI	Drug: Placebo MDI; Inhaled placebo administered as two puffs BID for 7 days
Active Comparator: Tiotropium bromide 18 μg (Spiriva Handihaler®); Tiotropium Bromide inhalation powder	Drug: Tiotropium bromide 18 μg (Spiriva Handihaler®); Inhaled tiotropium bromide 18 μg (Spiriva Handihaler®) administered QD for 7 days
Experimental: Inhaled PT001 (Dose 1); PT001 MDI Dose 1	Drug: PT001 MDI; Inhaled PT001 MDI administered as two puffs BID for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC 0-12 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	"Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Colin Reisner, M.D., Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• Reisner C, Fabbri LM, Kerwin EM, Fogarty C, Spangenthal S, Rabe KF, Ferguson GT, Martinez FJ, Donohue JF, Darken P, St Rose E, Orevillo C, Strom S, Fischer T, Golden M, Dwivedi S. A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Respir Res. 2017 Jan 6;18(1):8. doi: 10.1186/s12931-016-0491-8. Erratum In: Respir Res. 2017 Aug 21;18(1):158.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: March 9, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (Estimate): March 11, 2010

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tiotropium Bromide; Bromides; Formoterol Fumarate
• Other Study ID Numbers: PT0031002