The Effect of NAC on Lung Function and CT Mucus Score

N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus.
Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a
factor in chronic severe asthma as well. This role has been hard to prove because of
difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel
approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a
majority of people with severe asthma have at least one lung segment with a mucus plug and
27% have more than four lung segments with mucus plugs.

Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive
lung diseases, like Chronic Obstructive Pulmonary Disease (COPD). However, utilizing CT mucus
scores as a biomarker, investigators believe that mucolytic treatment may prove useful for
those with significant mucus impaction.

This is a randomized, double-blind, placebo-controlled phase 4 study of 20% NAC in patients
with asthma who also have evidence of mucus in their lungs as determined by CT imaging.
Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus
in the airways, with a mucolytic like NAC, will result in an improvement of lung function.

Inclusion Criteria:

1. Male or female between the ages of 18 and 80 years of age at Visit 1

2. Written informed consent obtained from subject and ability for subject to comply with
the requirements of the study.

3. Able to perform reproducible spirometry according to American Thoracic Society (ATS)
criteria

4. Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥
12% or hyperreactivity to methacholine reflected by a methacholine provocative
concentration that results in a 20% fall in FEV1(PC20) ≤ 16 mg/mL)

5. Clinical history of asthma per patient report or medical record

6. Pre-bronchodilator FEV1 > 35% predicted

7. Post-bronchodilator FEV1 > 40% but < 90% predicted

8. Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater

9. CT mucus score ≥ 5

10. Ability to tolerate study drug reflected by a post-treatment FEV1 ≥ 80% of pre-
treatment, pre-bronchodilator FEV1

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation
in the study

2. Presence of a condition or abnormality that in the opinion of the Investigator would
compromise the safety of the patient or the quality of the data

3. Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year
smoking history

4. Adherence to study drug ≤ 70% after first treatment period

5. Current participation in an investigational drug trial

6. Other chronic pulmonary disorders, including (but not limited to) cystic fibrosis,
chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction
(that is the sole cause of respiratory symptoms and at the PI's discretion), severe
scoliosis or chest wall deformities that affect lung function, or congenital disorders
of the lungs or airways

7. Unwillingness to follow study procedures

8. History of allergy or intolerance to study drug

9. Any other criteria that places the subject at unnecessary risk according to the
judgment of the Principal Investigator