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Trial registered on ANZCTR


Registration number
ACTRN12617001501336
Ethics application status
Approved
Date submitted
20/10/2017
Date registered
25/10/2017
Date last updated
12/11/2018
Date data sharing statement initially provided
6/11/2018
Date results information initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of Pirfenidone Solution for Inhalation in Healthy Volunteers, Smokers or Former Smokers with Decreased Lung function, and Patients with Idiopathic Pulmonary Fibrosis (IPF) to determine pharmacokinetics, as well as the safety and tolerability in volunteers with a history of smoking with decreased lung function and IPF patients.
Scientific title
A Phase 1 Study of AP01 (Aerodone™, Pirfenidone Solution for Inhalation) Delivered via the PARI eFlow® Nebulizer System in Healthy Volunteers, Smokers or Former Smokers with Decreased Lung Function, and Patients with Idiopathic Pulmonary Fibrosis (IPF) to determine pharmacokinetics, as well as the safety and tolerability in volunteers with a history of smoking with decreased lung function and IPF patients.
Secondary ID [1] 293176 0
Sponsor protocol number: AP01-001
Universal Trial Number (UTN)
U1111-1203-8329
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 305163 0
Condition category
Condition code
Respiratory 304485 304485 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drug: Inhaled Pirfenidone: Cohorts 1, 2 and 3, except those receiving placebo, will receive a single ascending dose, (25, 50, and 100 mg dose of pirfenidone, respectively). Cohorts 4 - 6, except those assigned to placebo in Cohort 5, will receive a single dose (25, 50,or 100 mg pirfenidone) of the maximum tolerated dose from the first three cohorts.
Drug: Salbutamol: Cohorts 1-3: If forced expiratory volume in one second (FEV1) in two or more subjects in any ascending dose cohort falls by greater than 10% at 15 minutes, all subsequent subjects will be pretreated with salbutamol. Otherwise, Cohort 4 will not receive pretreatment with salbutamol; Cohort 5 and Cohort 6 subjects with chronic obstructive pulmonary disease (COPD) or with a smoking history will receive pretreatment with 2 puffs (200µg) of salbutamol metered dose inhaler device within 30 minutes to inhalation of study drug.
Subjects will be trained to used the nebulizer upon admission to the Phase 1 facility. This single dose investigational product administration will be overseen by personnel at the Phase 1 facility.
Intervention code [1] 299423 0
Treatment: Drugs
Comparator / control treatment
Drug: Inhaled Placebo: Those assigned to placebo will receive a single dose of placebo. Placebo contains 5 mMol citrate buffer, 150 mMol NaCl, 0.225 mMol sodium saccharine and water, pH 6.0, filled to 9.0 mL
Control group
Placebo

Outcomes
Primary outcome [1] 303720 0
Evaluate the safety and tolerability of inhaled pirfenidone as measured by adverse events related to investigational product, lab parameters, Spirometry before and after drug administration (Cohort 4 excluded), Oximetry before and after drug administration, cardiac monitoring during bronchoscopy (Cohort 4 only)
Timepoint [1] 303720 0
Post-dose on Day 1
Upon Discharge on Day 2
At Follow-Up on Day 5, 6, or 7
Secondary outcome [1] 339958 0
Determine systemic and urine pharmacokinetics (PK) for each dose using Maximum Concentration (Cmax), Time to Peak Concentration (Tmax) and Area Under the Concentration – Time Curve from Time 0 to 24 Hours Post Dose (AUC(0-24) ). All PK parameters will be summarized using descriptive statistics and presented by time point. All PK parameters will be presented for individual subjects in data listings.
No PK data will be compiled for the placebo subjects.

Timepoint [1] 339958 0
Analysis of pirfenidone plasma concentrations prior to and at 10 minutes, 30 minutes, 1, 2, 4, 6, and 24 hours post-dose. Analysis of pirfenidone urine concentrations prior to and 0-6, 6-12, and 12-24 hours post-dose. Analysis of pirfenidone amounts in bronchoalveolar lavage fluid between 20 - 45 minutes post-dose (Cohort 4 only)
Secondary outcome [2] 339959 0
Determine maximum tolerated dose (MTD) of Aerodone™ in normal healthy volunteers (NHV). Tolerability of dose will be assessed by the Principal Investigator by reviewing adverse events, change in FEV1 and oximetry to determine either continuation of the cohort or dose escalation, respectively. A safety committee will be available to review the data for determination of cohort continuation and escalation, if needed. Potential dose limiting events are 1) Possible or probably drug related moderate or severe adverse event 2) Saturated Oxygen (SaO2) < 80% post dose, 3) IPF cohort only: SaO2 decrease > 10% from baseline (subjects may be on supplemental O2), or 4) FEV1 decrease of > 15% and symptomatic occurring after pretreatment with Salbutamol
Timepoint [2] 339959 0
Post-dose on Day 1
Upon Discharge on Day 2
At Follow-Up on Day 5, 6, or 7


Eligibility
Key inclusion criteria
1. Males or females 18 to 55 years
2. Female subjects must be:
• of non child-bearing potential [surgically sterilised or post–menopausal (12 months with no menses without alternative medical cause)] OR
• not pregnant, breast feeding or planning to become pregnant AND willing to comply with the medically acceptable contraceptive requirements of the study from Screening to at least 30 days after the last Investigational Medicinal Product (IMP) administration.
3. Must be able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form.Additional Inclusion Criterion for Cohort 5
4. Current or past smokers with > 20 pack year history of smoking and decreased lung function (FEV1 >= 50% predicted)
Additional Inclusion Criteria for Cohort 6
5. Diagnosis of IPF by American Thoracic Society (ATS) 2011 criteria
6. Males or females 18 to 70 years
7. For at least 2 subjects, > 20 pack year history of smoking
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of previous allergy or sensitivity to pirfenidone.
2. Use of oral pirfenidone within 2 days prior to admission to Phase 1 facility.
3. History of reactive airways disease (such as asthma or chronic obstructive pulmonary disease (COPD), cystic fibrosis, or bronchiectasis (Cohorts 1-4 only). Cohort 5 will exclude cystic fibrosis and bronchiectasis but will allow a history of COPD and Asthma.
4. Human Immunodeficiency Virus Positive Result (HIV+).
5. Active Hepatitis B or C.
6. Cigarette/e-Cigarette smoking or use of other nicotine or tobacco containing products within seven days prior to study drug administration (Cohorts 1-4 only).
7. Positive for drugs of abuse or alcohol use at screening or admission to Phase 1 facility. A breathalyzer test will be used to screen for the presence of alcohol. A urine standard panel will be used to test for the following substances (with repeat testing for confirmation, as needed) (Cohorts 1-5 only):
• Opiates
• Methadone
• Cocaine
• Tetrahydrocannabinol
• Benzodiazepines
• Amphetamines / Methamphetamines
• Barbiturates
• 3,4-methylenedioxy-methamphetamine
• Phencyclidine
8. Participation in a clinical study with administration of an investigational drug product within the previous 30 days, or five half-lives (T1/2) of the previously administered investigational product.
9. Donation of blood or significant blood loss within the 8 weeks prior to admission to Phase 1 facility.
10. Donation of plasma within the week prior to admission to Phase 1 facility.
11. Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk.
12. Pregnant or nursing.
13. Use of any medication in the opinion of the Principal Investigator that that might interact with study medication or may lead to abnormal chemistry of hematology tests.
14. Clinically significant abnormality in the opinion of the Principal Investigator in baseline hematology or chemistry tests.


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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9214 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 17869 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 297804 0
Commercial sector/Industry
Name [1] 297804 0
Avalyn Pharma Pty Ltd
Address [1] 297804 0
Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country [1] 297804 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Avalyn Pharma Pty Ltd
Address
Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country
Australia
Secondary sponsor category [1] 296845 0
None
Name [1] 296845 0
Address [1] 296845 0
Country [1] 296845 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298863 0
Alfred Health HREC
Ethics committee address [1] 298863 0
The Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Ethics committee country [1] 298863 0
Australia
Date submitted for ethics approval [1] 298863 0
Approval date [1] 298863 0
23/10/2017
Ethics approval number [1] 298863 0

Summary
Brief summary
A Phase 1, Randomized, Double-Blinded Study of AP01 (Aerodone, Pirfenidone Solution for Inhalation) Delivered via the PARI eFlow Nebulizer System in Healthy Volunteers, Smokers or Former Smokers with Decreased Lung function, and Patients with Idiopathic Pulmonary Fibrosis to determine the Pharmacokinetics and Maximum Tolerated Dose, as well as the Safety and Tolerability in IPF patients
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78474 0
Dr Jason Lickliter
Address 78474 0
Nucleus Network, Level 5, Burnet Building, AMREP Precinct, 89 Commerical Rd, Melbourne, VIC 3004
Country 78474 0
Australia
Phone 78474 0
+61 3 9076 8960
Fax 78474 0
Email 78474 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 78475 0
Dr Bruce Montgomery
Address 78475 0
Avalyn Pharma Pty Ltd, Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country 78475 0
Australia
Phone 78475 0
+61 3 9869 5922
Fax 78475 0
Email 78475 0
bmontgomery@avalynpharma.com
Contact person for scientific queries
Name 78476 0
Dr Bruce Montgomery
Address 78476 0
Avalyn Pharma Pty Ltd., Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country 78476 0
Australia
Phone 78476 0
+61 3 9869 5922
Fax 78476 0
Email 78476 0
bmontgomery@avalynpharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study completed prior to requirement.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 112 0
Conference poster
Citation/DOI/link/details [1] 112 0
ICLAF 2018 Conference Poster: Phase 1 Dose Escalation Study of Aerosolized Pirfenidone in Normal Healthy Volunteers, Smokers, and IPF patients. Presented by Ian Glaspole.
Results – plain English summary