NAC Phase IIB: A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients

Study Overview
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Brief Summary
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This Phase IIB proof-of-concept study would examine the effects of an investigational product called N-acetylcysteine (NAC) on the basic processes that cause inflammation in CF lung disease. We hope to learn more about the causes of lung disease in cystic fibrosis by studying the characteristics of the inflammation in the lungs of patients who have CF.

Official Title
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A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: N-acetylcysteine (NAC)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 7 years of age or older Diagnosis of CF based upon the following criteria: One or more clinical features characteristic of CF AND (b or c) Positive sweat test > 60 mEq/L by quantitative pilocarpine iontophoresis A genotype with two identifiable mutations consistent with CF Written informed consent (and assent when applicable) obtained from subject or subject's legal representative Clinically stable with no evidence of acute upper or lower respiratory tract infection within 4 weeks prior to enrollment Stable mild or moderately severe lung disease defined by an FEV1 > or = 40% and < or = 85% predicted for age based on the Wang (males < 18 years, females < 16 years) or Hankinson (males > or = 18 years, females > or = 16 years) standardized equations Able to tolerate sputum induction with 3% hypertonic saline and to expectorate Able to perform repeatable, consistent efforts in pulmonary function testing Weight > or = 25 kg at time of enrollment Females of child bearing potential must be willing to use birth control (IUD, oral, transdermal, or parenteral contraceptives; abstinence) Exclusion Criteria: Clinically significant liver enzymes (AST, ALT or GGT) > 2.5 times the upper limit of normal at screening History of ABPA, unless have evidence of a stable IgE (< 5% increase compared to previous test) for 6 months prior to enrollment Current or history of rheumatic or collagen vascular disorders Use of NSAIDS other than for chronic therapy within 1 week prior to enrollment Initiation of chronic therapy with ibuprofen, azithromycin, TOBI® or Aztreonam within 6 weeks prior to enrollment Consumption or inhalation of antioxidants (including NAC, GSH, Immunocal, Nacystelyn, pentoxyfilline) within 6 weeks prior to enrollment Use of oral or IV corticosteroids within 4 weeks prior to enrollment Use of acetaminophen within 3 days prior to enrollment Unable to forego during the study: Vitamin E: more than 400 IU/day for subjects < or = 12 years of age and 800 IU/day for subjects > 12 years of age Vitamin C: more than 0.5 gm/day More than two alcoholic drinks per day Known hypersensitivity to oral PharmaNAC® Current cigarette consumption Pregnant or breastfeeding Subject unlikely to complete the study as determined by the Investigator Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject Participation in trials for other anti-inflammatory or therapeutic investigational drugs within 6 weeks prior to enrollment

Ages Eligible for Study
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Minimum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo was administered oral tablet TID for 24 weeks. | Drug: Placebo<br> <br> |
| Active Comparator: N-Acetylcysteine<br>Participants received 900 mg of oral N-acetylcysteine TID for 24 weeks. | Drug: N-acetylcysteine (NAC)<br> <br> * Other names: PharmaNAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum | (change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group) | From enrollment to end of the 24-week trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 (Percent of Predicted for Age) | Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted) | From enrollment to the end of the 24-week trial | 
| FEV1 (L) | Forced expiratory volume in 1 second (Liters) | Baseline to end of study (24 weeks) | 
| FEF 25-75% (L/Sec) | Difference in mid-expiratory flow rates between 25 to 75% of the vital capacity, in L/sec measured at the beginning of the study to the end of the study. | Baseline to end of study (24 weeks) | 
| FEF 25-75% (Percent of Predicted) | Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to the end of study (24 weeks). | Baseline to 24 weeks |