None listed
Conditions
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
Interventions
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 gr
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.
Sponsors
Avalyn Pharma Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
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.
Outcome results
None listed