Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000191291
Ethics application status
Approved
Date submitted
16/01/2009
Date registered
20/04/2009
Date last updated
29/11/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomized, Double-blind, Placebo and Active-controlled, Cross-over, Multi-centre, Study with Five Single Dose Treatment Periods Evaluating Single Administration of Three Doses of Inhaled PT005 in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD), Compared to Open-Label Marketed Formoterol (FORADIL AEROLIZER 'Registered Trade Mark') as an Active Control.
Scientific title
A Randomized, Double-blind, Placebo and Active-controlled, Cross-over, Multi-centre, Study with Five Single Dose Treatment Periods Evaluating Single Administration of Three Doses of Inhaled PT005 in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD), Compared to Open-Label Marketed Formoterol (FORADIL AEROLIZER 'Registered Trade Mark') as an Active Control evaluating the changed in Forced Expiratory Volume.
Secondary ID [1] 778 0
Pearl Therapeutics, Inc Study PT0050801
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 4196 0
Condition category
Condition code
Respiratory 4380 4380 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Foradil Aerolizer (12 micrograms formoterol fumarate dry powder for inhalation) is an inhaled long acting bronchodilator medication that is indicated for asthma and chronic obstructive pulmonary disease (COPD). PT005 is an inhaled long acting bronchodilator. The design uses ascending doses of PT005 (3, 6 and 12 micrograms) with a full crossover. There are 5 single days of treatment with a minimum of 3 days and maximum of 10 days between treatments. The Foradil Aerolizer is administered as per the instructions for use with one inhalation.
Intervention code [1] 3890 0
Treatment: Drugs
Comparator / control treatment
The clinical trial is placebo controlled. Each subject will receive a single dose of placebo in a random order. Subjects will not know whether they are receiving placebo or PT005, as the clinical trial is blinded. The placebo is formulated in the same way as PT005, however it does not contain active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 5258 0
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. The outcome will be assessed by the evaluation of serial spirometry at pre-defined intervals over 12 hours.
Timepoint [1] 5258 0
On each of five single dose test days, spirometry assessments will be obtained prior to dosing and then at pre-defined intervals over 12 hours. This information will be used to calculate the forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours [AUC(0-12)].
Secondary outcome [1] 8859 0
Time to onset of action (>10% improvement in mean forced expiratory volume in one second (FEV1) from test day baseline). Change in mean peak expiratory flow rate (PEFR) over time from test day baseline. Change in mean forced vital capacity (FVC) from test day baseline. Changes in mean peak Inspiratory Capacity (IC). The outcome will be assessed by the evaluation of spirometry.
Timepoint [1] 8859 0
Secondary timepoint: On each of five single dose test days, spirometry assessments will be obtained prior to dosing and then at pre-defined intervals over 12 hours. This information will be used to calculate the time to onset of action, peak expiratory flow rate (PEFR), forced vital capacity (FVC) and inspiratory capacity (IC).
Secondary outcome [2] 8860 0
Comparison of safety parameters [electrocardiograms (ECG), vital signs, clinical laboratory testing, dry mouth assessments, adverse events (AEs)] between treatments. Vital signs, dry mouth assessments (if present will be asked if mild, moderate or severe) electrocardiograms (using an electrocardiogram machine) and physical exams will be conducted by a healthcare professional. Laboratory testing will be evaluated by taking blood samples.
Timepoint [2] 8860 0
Electrocardiograms (ECGs) and vital signs will be obtained at baseline prior to study drug administration, and then at specified intervals over 12 hour after study drug administration on all test days. Laboratory testing will be done at baseline prior to study drug administration and then four hours after study drug administration on all test days. Dry mouth will be evaluated at baseline prior to study drug administration, and then at specified intervals over 24 hours on all test days. Adverse events (AEs) will be evaluated throughout the study.
Secondary outcome [3] 8861 0
Non-compartmental analyses will be applied to determine the following pharmacokinetic outcomes: time to maximum concentration (Tmax), maximum concentration (Cmax), elimination coefficient (Ke), half life (T1/2) and area under the curve from time 0 to the last measurable concentration [AUC(0-t)] and area under the curve from time 0 to infinity [AUC(0-infinity)]. These parameters will be calculated for the three doses of inhaled PT005 as well as the active comparator.
Timepoint [3] 8861 0
Blood samples will be evaluated on each of the five test days prior to dosing and at specified intervals over 12 hours after study drug administration to calculate the pharmacokinetics outcomes.

Eligibility
Key inclusion criteria
1. Established clinical history of chronic obstructive pulmonary disease (COPD) in accordance with the American Thoracic Society/ European Respiratory Society criteria

2. Current or prior history of at least 10 pack-years of cigarette smoking. It should be noted that number of pack years = (number of cigarettes per day/ 20) X number of years smoked. For example, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to visit 1;

3. A measured post-salbutamol FEV1/FVC ratio of less than or equal to 0.70 at Visit 1 (Screening);

4. A measured post-salbutamol FEV1 greater than or equal to 40% and less than or equal to 80% of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES) III references equations at Visit 1 (Screening);

5. Demonstrated reversiblity to a short acting beta agonist (>12% and >150 ml improvement in baseline FEV1 30 minutes following administration of 4 puffs of salbutamol MDI, or > 200 ml improvement in baseline FEV1, 30 minutes following administration of 4 puffs of salbutamol metered dose inhaler (MDI)
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Primary diagnosis of asthma. Patients with a prior history of asthma are eligible if chronic obstructive pulmonary disease (COPD) is currently their primary diagnosis;

2. Active tuberculosis, lung cancer, bronchietasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease or other active pulmonary disease;

3. Lung volume reduction surgery at any time in the past;

4. Chest X-ray [or Computed Tomography (CT) scan] reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD;

5. Hospitalization due to poorly controlled COPD within 24 weeks of the screening visit;

6. Poorly controlled COPD, defined as the occurrence of any of the following in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 2:

a. Acute worsening of COPD that is managed with corticosteroids or antibiotics; or

b. Acute worsening of COPD that requires treatment prescribed by a physician;

7. Clinically significant medical conditions including but not limited to cardiovascular, neurological, psychiatric, renal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled;

8. Lower respiratory tract infections which requires the use of antibiotics within 6 weeks prior to Visit 1;

9. Abnormal and clinically significant 12-lead ECG that results in an active medical condition;

10. Treatment with tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, beta-adrenergic antagonists, anticonvulsants (barbiturates, hydantoins and carbamazepine) or phenothiazines would be ineligible for the study;

11. Non-compliance with study procedures, including an inability to abstain from smoking throughout each test day.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be randomly allocated to a study treatment sequence. Allocation was concealed by using numbered containers. After the enrolment (inclusion/exclusion) criteria have been reviewed to confirm eligibility and informed written consent has been obtained from the patient at screening, the Investigator or Study Coordinator will allocate a sequential subject identification number (patient number) to the patient. Subject assignment will be made by selecting the treatment kit with lowest number in the sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The study statistician was responsible for preparing the randomization schedule. A randomization sequence was generated using a randomisation table created by computer software (i.e., computerised sequence generation). The randomization schedule was used to prepare study drug packs for each patient.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/10/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 1515 0
New Zealand
State/province [1] 1515 0

Funding & Sponsors
Funding source category [1] 4347 0
Commercial sector/Industry
Name [1] 4347 0
Pearl Therapeutics Inc.
Country [1] 4347 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Pearl Therapeutics Inc.
Address
200 Saginaw Drive,
Redwood City,
CA 94063
Country
United States of America
Secondary sponsor category [1] 3916 0
Commercial sector/Industry
Name [1] 3916 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 3916 0
Level 3,
88 Jephson St,
Toowong, QLD 4066
Country [1] 3916 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The primary purpose of this study is to compare the safety and improvement in lung function in patients with chronic obstructive pulmonary disease (COPD) following administration of inhaled PT005 to inhaled placebo. The safety and improvement in lung function will also be compared to a known and approved inhaled bronchodilator (Foradil Aerolizer) for the treatment of patients with chronic obstructive pulmonary disease (COPD). The primary hypothesis is that inhaled PT005 will be safe, well tolerated and will demonstrate greater improvement in lung function compared to placebo, and these improvements will be comparable to Foradil Aerolizer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35072 0
Address 35072 0
Country 35072 0
Phone 35072 0
Fax 35072 0
Email 35072 0
Contact person for public queries
Name 12419 0
Caron Hookway
Address 12419 0
Level 3, 88 Jephson St
Toowong, QLD 4066
Country 12419 0
Australia
Phone 12419 0
+61 7 3331 3933
Fax 12419 0
+61 7 3870 0520
Email 12419 0
[email protected]
Contact person for scientific queries
Name 3347 0
Caron Hookway
Address 3347 0
Level 3, 88 Jephson St
Toowong, QLD 4066
Country 3347 0
Australia
Phone 3347 0
+61 7 3331 3933
Fax 3347 0
+61 7 3870 0520
Email 3347 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.