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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001341314
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
26/09/2026
Date registered
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9/11/2026
Date last updated
Help: Date last updated
9/11/2026
Date data sharing statement initially provided
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9/11/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
Evaluation of the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of AP03 (pirfenidone/nintedanib inhalation solution) in healthy volunteers.
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of AP03 (Pirfenidone/Nintedanib Inhalation Solution) Delivered via the eFlow® Nebulizer System in Healthy Volunteers.
Additional trial identifiers [1] 318500 0
AP03-001
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Healthy Participants 343675 0
Condition category
Condition code
Respiratory 340151 340151 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
SAD: Single Ascending Dose will be conducted in up to 3 dose cohorts of 8 healthy volunteers each. The study will evaluate multiple dose levels of the combination therapy (pirfenidone/nintedanib), beginning at a low dose (50 mg pirfenidone/2 mg nintedanib) and escalating as appropriate. For each component, the dose will not exceed the highest dose currently being evaluated in the respective ongoing Phase 2 monotherapy (pirfenidone alone [100 mg] or nintedanib alone [4 mg]) studies.

MAD: Multiple Ascending Dose will be conducted in up to 3 cohorts of 8 healthy volunteers each, for a multiple-dose (7-day) treatment period. The healthy volunteer MAD portion will begin at doses no greater than those achieved in the SAD cohorts up to a maximum of the highest doses currently being studied in the respective ongoing Phase 2 monotherapy studies. 

The registration numbers of the ongoing Phase 2 monotherapies are as follows:
AP01: NCT06329401.
AP02: NCT07194382.

The study medicine (AP03 or placebo) is administered using the eFlow nebulizer. The eFlow nebulizer is a small, handheld, battery-powered device that turns liquid medication into a fine mist that can be breathed in. It has two parts: a handset that holds the medicine and a small control unit that powers it.
When the eFlow Nebulizer is switched on, a thin metal disc with tiny holes vibrates very quickly and pushes the liquid through the holes, turning it into a mist. The participant breathes in the mist through a mouthpiece while breathing normally, until the device signals that the dose is finished.
Nebulization is anticipated to take approximately 10 minutes. The nebulizer will automatically turn off when the medication is fully nebulized or after a maximum of 20 minutes.

Depending on available safety data, the Sponsor along with the Safety Review Committee (SRC) may decide to eliminate doses or expand dosing cohorts.

Adherence to the intervention will be monitored through direct administration of all doses by qualified study personnel at the Clinical Research Unit. Dosing will be documented in source records and drug accountability records, and participants will be monitored according to the protocol-defined schedule.
Intervention code [1] 335398 0
Treatment: Drugs
Intervention code [2] 335518 0
Treatment: Other
Description of the comparator or control
The placebo used is a sterile aqueous solution containing riboflavin, glycine, propylene glycol, sodium chloride, sodium saccharin dihydrate, hydrochloric acid (pH adjustment), and water, with no active medicinal ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 347004 0
SAD: Composite assessment of safety and tolerability following single ascending dose administration of AP03, evaluated by the incidence of adverse events (AEs), changes in clinically significant vital signs, electrocardiograms (ECGs), clinical laboratory parameters and physical examination and spirometry.
Timepoint [1] 347004 0
AEs: Adverse events will be reported by the volunteer/participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative) ad hoc and queried throughout the study. Vital Signs: At Day -28 (Screening), and then daily from Day 1 to Day 5 (FUP visit). Vital signs will be performed pre-dose (within 1 hour) and then 15 minutes (±10 min) and 30 minutes (±10 min) post-end-of-nebulization for all cohorts. Electrocardiograms (ECGs): Day -28 (screening) and Day 1. Laboratory parameters: Days -28 (Screening), 1, and Day 3 (Discharge). Physical Examination: Days -28 (Screening), 1, 3 (Discharge) and Day 5 (Follow-up Visit). Spirometry: Days -28 (Screening) and Day 1.
Primary outcome [2] 347005 0
MAD: Composite assessment of safety and tolerability following Multiple ascending dose administration of AP03, evaluated by the incidence of adverse events (AEs), changes in clinically significant vital signs, electrocardiograms and Spirometry
Timepoint [2] 347005 0
AEs: Adverse events will be reported by the volunteer/participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative) ad hoc and queried throughout the study. Vital Signs: At Day -28 (Screening), and then daily from Day 1 to Day 14 (FUP visit). Vital signs will be performed pre-dose (within 1 hour) and then 15 minutes (±10 min) and 30 minutes (±10 min) post-end-of-nebulization for all cohorts Electrocardiograms (ECGs): Days -28 (screening), 1 and Day 7. Laboratory parameters: Days -28 (Screening), 1, 3, 5, 9 (Discharge) and Day 14 (Follow-up Visit). Physical Examination: Days -28 (screening), 1 and Day 9 (Discharge) Spirometry: Days -28 (Screening), 1, 3 and Day 7.
Secondary outcome [1] 468536 0
SAD: Pharmacokinetics (PK) of pirfenidone and nintedanib (and metabolites) following single-dose administration of AP03
Timepoint [1] 468536 0
Days 1, 2 and Day 3. (Within 1 hour prior to dosing and at 10 minutes, 30 minutes, 1, 2, 4, 8, 12, 24, 30 and 48 hours post-end-of-nebulization)
Secondary outcome [2] 468537 0
MAD: Pharmacokinetics (PK) of pirfenidone and nintedanib (and metabolites) following multiple-dose administration of AP03
Timepoint [2] 468537 0
Day 1 and Day 7: within 1 hour prior to dosing and at 10 minutes, 30 minutes, 1, 2, 4, 8 and 12 hours post-dose; Day 2 and Day 5: within 1 hour prior to dosing; Day 8: 24 and 30 hours post-dose; Day 9: 48 hours post-dose.

Eligibility
Key inclusion criteria
1. Female volunteers/participants must be of non-childbearing potential [surgically sterilized or post–menopausal (12 months with no menses without alternative medical cause)
2. Volunteer/participant’s BMI is between 18 and 32 kg/m2
3. Have not had any vaccine (including COVID-19, influenza virus, and respiratory syncytial virus [RSV]) within 7 days prior to the AP03 dose (Day 1) and, are willing to forgo any vaccine until after the follow-up visit.
4. Forced Vital Capacity (FVC) more than or equal to 80% predicted normal.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Healthy volunteers
Yes
Key exclusion criteria
1. Women of childbearing potential are excluded
2. History of previous allergy to pirfenidone or nintedanib. This includes proven or suspected photosensitivity to pirfenidone.
3. Human Immunodeficiency Virus Positive
4. Active Hepatitis B (HBsAg positive) or C (HCV RNA positive) infection.
5. Aspartate aminotransferase or alanine aminotransferase (AST or ALT) > 1.5X upper limit of normal.
6. Use of anticoagulant or antiplatelet drugs with the exception of aspirin at a dose of less than or equal to 75mg daily.
7. Use of oral pirfenidone and/or nintedanib within 90 days prior to admission to the Phase 1 facility.
8. Donation of blood within 30 days prior to admission to the Phase 1 facility, or significant blood loss within 8 weeks prior to admission to the Phase 1 facility.
9. Any diagnosed respiratory disease such as clinically significant pulmonary hypertension, asthma requiring inhaled or systemic medication, COPD or bronchiectasis (Cystic Fibrosis [CF] or non-CF bronchiectasis). Volunteers/participants with fully resolved childhood asthma with no recurrences or medical needs as an adult are permitted.

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)
The randomization scheme will be generated prior to the initiation of the study by an independent statistician who will not be a member of the study team and provided only to the unblinded pharmacist
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization sequence is generated by an unblinded statistician using a predefined randomization
schedule.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/11/2026
Actual
Date of last participant enrolment
Anticipated
13/05/2027
Actual
Date of last data collection
Anticipated
22/05/2027
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 323077 0
Commercial sector/Industry
Name [1] 323077 0
Avalyn Pharma Pty Ltd
Country [1] 323077 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Avalyn Pharma Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 326025 0
None
Name [1] 326025 0
Address [1] 326025 0
Country [1] 326025 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321478 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 321478 0
Ethics committee country [1] 321478 0
Australia
Date submitted for ethics approval [1] 321478 0
24/09/2026
Approval date [1] 321478 0
22/10/2026
Ethics approval number [1] 321478 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 153846 0
Dr Christina Chang
Address 153846 0
Nucleus Network Melbourne- Level 3/549 St Kilda Rd, Melbourne VIC 3004, Australia
Country 153846 0
Australia
Phone 153846 0
+61 429 001 089
Fax 153846 0
Email 153846 0
[email protected]
Contact person for public queries
Name 153847 0
Dr. Christina Chang
Address 153847 0
Nucleus Network Melbourne- Level 3/549 St Kilda Rd, Melbourne VIC 3004, Australia
Country 153847 0
Australia
Phone 153847 0
+61 429 001 089
Fax 153847 0
Email 153847 0
[email protected]
Contact person for scientific queries
Name 153848 0
Craig S. Conoscenti
Address 153848 0
Avalyn Pharma, 245 First Street, 18th Floor, Cambridge, MA 01242
Country 153848 0
United States of America
Phone 153848 0
+01 203 482 3219
Fax 153848 0
Email 153848 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No



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.