Study to Evaluate the Safety and Efficacy of Inhaled PT005 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-blind, Five-period, Placebo and Active-controlled,Cross-over, Multi-centre, Study Evaluating Single Administration of Three Doses of Inhaled PT005 in Patients With Moderate-to-Severe COPD, Compared to Open- Label Marketed Formoterol (FORADIL® AEROLIZER®) as an Active Control

The purpose of this study is to evaluate the safety and efficacy of inhaled PT005 compared to placebo and Formoterol Fumarate (Foradil Aerolizer) in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Inhaled PT005; Drug: Inhaled placebo; Drug: Formoterol Fumarate 12 mcg (Foradil Aerolizer)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Glebe, New South Wales, Australia, 2037
      • Woolcock Institute of Medical Research
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Australian Clinical Research Organisation
    • South Brisbane, Queensland, Australia, 4101
      • Mater Hospital
• New Zealand
  • Christchurch, New Zealand, 8014
    • Primorus Clinical Trials
  • Wellington, New Zealand, 6035
    • P3 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
• Fluency in written and spoken English
• 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-salbutamol FEV1/FVC ratio of < or = 0.70
• A measured post-salbutamol FEV1 > or = 40 and < or = 80% of predicted normal values
• Demonstrated reversibility to a short acting beta agonist by either >12% and >150 ml improvement in baseline FEV1, 30 minutes following administration of 4 puffs of salbutamol MDI or an absolute improvement of >200 ml in baseline FEV1, 30 minutes following administration of 4 puffs of salbutamol MDI.
• Competent at using the inhalation device

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
• 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
• 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 any study drug component
• History of severe milk protein allergy
• Known or suspected history of alcohol or drug abuse
• Medically unable to withhold short acting bronchodilators for 8-hours
• Use of the medications below in specified time interval prior to Screening: 12-weeks: depot corticosteroids, intra-articular corticosteroids; 4 weeks: ICS >1000 μg/day of fluticasone propionate or equivalent, non-potassium sparing diuretics, P-glycoprotein inhibitors, CYP3A4 inhibitors; 1 week: tiotropium; 48 hours: oral beta agonists, long acting beta agonists, theophylline, zariflukast, montelukast, zileuton; 8 hours: ipratropium or ipratropium/salbutamol combination product, inhaled short acting beta agonists, xanthine containing foods
• 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 or will enter acute phase of pulmonary rehabilitation program during study
• Unable to comply with study procedures
• Affiliated with Investigator site
• Questionable validity of consent
• A positive drug of abuse test at Screening lives prior to Screening, whichever is longer

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Inhaled PT005 2.4 mcg	Drug: Inhaled PT005; single dose, inhaled
Experimental: 2; Inhaled PT005 4.8 mcg	Drug: Inhaled PT005; single dose, inhaled
Experimental: 3; Inhaled PT005 9.6 mcg	Drug: Inhaled PT005; single dose, inhaled
Placebo Comparator: 4; Inhaled Placebo	Drug: Inhaled placebo; single dose, inhaled
Active Comparator: 5; Formoterol Fumarate 12 mcg (Foradil Aerolizer)	Drug: Formoterol Fumarate 12 mcg (Foradil Aerolizer); single dose, Formoterol Fumarate 12 mcg administered via the Aerolizer; Other Names: Foradil Aerolizer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours [AUC(0-12)] from test day baseline across the three doses of inhaled PT005 compared with placebo.	Serial FEV1 measured over 12 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to onset of action (>10% improvement in FEV1 from baseline)	Serial FEV1 measured over 12 hours
Peak FEV1	Serial FEV1 measured over 12 hours
Trough FEV1	Serial FEV1 measured over 12 hours
Peak inspiratory capacity (IC)	Serial IC measured over 12 hours
Peak expiratory flow rate (PEFR)	Serial PEFR measured over 12 hours
Forced vital capacity (FVC)	Serial FVC measured over 12 hours

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Quinn D, Seale JP, Reisner C, Fischer T, Golden M, Fernandez C, Darken P, St Rose E, Thomas M, Tardie G, Orevillo C. A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD. Respir Med. 2014 Sep;108(9):1327-35. doi: 10.1016/j.rmed.2014.06.009. Epub 2014 Jul 3. Erratum In: Respir Med. 2015 Oct;109(10):1369.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: April 9, 2009
• First Submitted That Met QC Criteria: April 10, 2009
• First Posted (Estimate): April 13, 2009

Study Record Updates

• Last Update Posted (Estimate): October 13, 2010
• Last Update Submitted That Met QC Criteria: October 11, 2010
• Last Verified: October 1, 2010

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; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: PT0050801