A Study to Assess the Tolerability of a Single Dose of AF-219 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

This study assesses the tolerability of a single dose of AF-219 in participants with
idiopathic pulmonary fibrosis (IPF).

This will be the first experience of administering AF219 in patients with IPF. P2X3
receptors are found on the chemosensory afferents of the carotid body and can influence
sympathetic autonomic discharge, especially in sensitized subjects; accordingly, by blocking
these P2X3 receptors, AF-219 may have an effect of reducing sympathetic activity. Therefore
in order to determine whether P2X3 antagonism would have an effect on the hemodynamic
measures such as blood pressure in patients with IPF, study AF219-019 is being performed.
These patients will be closely monitored in order to determine any such effect.

Inclusion Criteria:

- Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society
(ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin
American Thoracic Society (ALAT) IPF 2011 guideline

- Life expectancy of greater than 6 months

- Stable medical condition (IPF) for at least 4 weeks

- Women of child-bearing potential must use 2 forms of an acceptable birth control
method from Screening through the Follow-Up Visit

- Male subjects and their partners of child-bearing potential must use 2 methods of
acceptable birth control, 1 of which must be a barrier method, and make no donation
of sperm from Screening until 3 months after the last dose of study drug

- Written informed consent

- Willing and able to comply with all aspects of the protocol

Exclusion Criteria:

- Current smoker (i.e., within the last 30 days)

- Initiation of treatment with an antihypertensive agent within 4 weeks prior to the
day of dosing (Day 1) or during the study

- History of upper respiratory tract infection within 4 weeks of the day of dosing (Day
1)

- Requiring concomitant therapy with prohibited medications

- Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2

- History of concurrent malignancy or recurrence of malignancy within 2 years prior to
Screening (not including subjects with <3 excised basal cell carcinomas)

- History of a diagnosis of drug or alcohol dependency or abuse within approximately
the last 3 years

- Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty,
fundoplication, any type of bariatric surgery, vagotomy, or bowel resection)

- Recent history of stroke or transient ischemic attack (within 6 months prior to
Screening) not due to trauma, repaired vascular malformation, or aneurysm

- Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure
(DBP) >90 mm Hg

- QTc interval >450 milliseconds in males, >470 milliseconds in females

- Breastfeeding

- Treatment with an investigational drug or biologic within 30 days preceding the first
dose of study medication or plans to take another investigational drug or biologic
within 30 days of study completion

- Blood donation within 56 days or plasma donation within 7 days prior to dosing

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with trial participation or
investigational product administration or may interfere with the interpretation of
trial results and, in the judgment of the Investigator or Sponsor, would make the
subject inappropriate for entry into this trial