Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in People With Idiopathic Pulmonary Fibrosis

IPF is a disease in which fibrous tissue clogs and damages the air sacs within the lungs.
Widespread and permanent scarring and stiffening of lung tissue eventually results.
Individuals with IPF may experience breathing difficulties, cough, chest pain, and a
decreased exercise capacity. Although the cause of IPF is not definitively known, it may be
a result of an inflammatory response to an unknown substance. There is no cure for IPF, and
no approved treatment for the disease. NAC, an antioxidant that is effective at loosening up
mucus that forms in the lungs, may improve lung function. The purpose of this study is to
evaluate the effectiveness of NAC at preventing the loss of lung function in people with
IPF.

This study will enroll people with mild to moderate IPF. Participants will be randomly
assigned to receive for 60 weeks either NAC alone or placebo. Study visits will occur at
baseline and Weeks 4, 15, 30, 45, and 60. At all study visits, a physical exam and blood
collection will occur. At selected visits, the following study procedures will occur: lung
function testing; urine collection; a 6-minute walk test, which will measure the distance
walked in a 6-minute period; and questionnaires to assess health status, breathing, and
quality of life. Participants will record medication usage and symptoms in a daily diary.
Study researchers will review medical records and the Social Security death index 5 years
after the end of the study to determine the incidence of death among study participants.

Inclusion Criteria:

- Forced vital capacity (FVC) greater than or equal to 50% of predicted value

- Diffusion capacity (DLCO) greater than or equal to 30% of predicted value

- Diagnosis of IPF by modified American Thoracic Society (ATS) criteria in the 48
months before study entry

Exclusion Criteria:

- History of clinically significant environmental exposure known to cause pulmonary
fibrosis

- Diagnosis of connective tissue disease as the likely cause of the interstitial
disease

- Extent of emphysema greater than the extent of fibrotic change (i.e., honeycombing,
reticular changes) on high resolution computed tomography (HRCT) scan

- Forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.65 at the time of
screening (post-bronchodilator)

- Partial pressure of arterial oxygen (PaO2) less than 55 mm Hg (less than 50 mm Hg at
Denver study site)

- Residual volume greater than 120% predicted at the time of screening
(post-bronchodilator)

- Evidence of active infection

- Significant bronchodilator response on screening spirometry, defined as change in
FEV1 greater than or equal to 12% and absolute change greater than 200 mL OR change
in FVC greater than or equal to 12% and absolute change greater than 200 mL

- Screening and baseline FVC measurements (in liters, post-bronchodilator) differing by
11%

- Listed for lung transplantation

- History of unstable or deteriorating cardiac disease

- Heart attack, coronary artery bypass, or angioplasty in the 6 months before study
entry

- Unstable angina pectoris or congestive heart failure requiring hospitalization in the
6 months before study entry

- Uncontrolled arrhythmia

- Severe uncontrolled high blood pressure

- Known HIV or hepatitis C

- Known cirrhosis and chronic active hepatitis

- Active substance and/or alcohol abuse

- Pregnant or breastfeeding

- Women of childbearing potential who are not using a medically approved means of
contraception

- Any clinically relevant lab abnormalities, including the following:

1. Creatinine greater than twice the upper limit of normal (ULN)

2. Hematology outside of specified limits

1. White blood cells less than 3,500/mm3

2. Hematocrit less than 25% or greater than 59%

3. Platelets less than 100,000 mm3 at the time of screening

3. Any of the following liver function test criteria above specified limits

1. Total bilirubin greater than twice the ULN

2. Aspartate (AST) or alanine aminotransferases (ALT) greater than 1.5 the ULN

3. Alkaline phosphatase greater than three times the ULN

4. Albumin less than 3.0 mg/dL at the time of screening

- Known hypersensitivity to study medication

- Any condition other than IPF that, in the opinion of the site PI, is likely to result
in death in the 1 year after study entry

- Any condition that, in the judgment of the PI, might cause participation in this
study to be detrimental or makes the person a poor candidate for the study