Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis

Inclusion Criteria:

• Male or female ≥10 years of age

• Documentation of a Cystic Fibrosis (CF) diagnosis as evidenced by 1 or more clinicalfeatures consistent with the CF phenotype and 1 or more of the following criteria:

• Sweat chloride equal to or greater than 60 milliequivalent (mEq/L) byquantitative pilocarpine iontophoresis test (QPIT)

• 2 well-characterized mutations in the cystic fibrosis transmembrane conductanceregulator (CFTR) gene

• Pancreatic insufficiency documented by having a spot fecal elastase-1 (FE-1) ≤ 100μg/gin a stool sample done either historically or at the screening visit

• Clinically stable with no significant changes in health status within 2 weeks prior torandomization

• Forced expiratory volume over one second (FEV1) ≥ 40 and ≤ 100% of predicted for agebased on the Wang (males < 18 years,females < 16 years) or Hankinson (males ≥ 18years, females ≥ 16 years) standardized equations at the screening visit

• Weight ≥ 30 kg at the screening visit

• Able to perform repeatable, consistent efforts in pulmonary function testing

• Able to tolerate sputum induction with 3% hypertonic saline and to expectorate withinduction

• Written informed consent (and assent when applicable) obtained from subject orsubject's legal representative

• Ability to swallow softgel capsules

Exclusion Criteria:

• Subjects being treated with ivacaftor (Kalydeco™)

• Liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), orgamma-glutamyl transferase (GGT) > 3 times the upper limits of normal at the screeningvisit

• Use of antibiotics (oral, iv, and/or inhaled) for acute respiratory symptoms within 2weeks prior to randomization

• Active treatment for allergic bronchopulmonary aspergillosis (ABPA)

• Current use of oral corticosteroids in doses exceeding the equivalent of 10 mgprednisone/day or 20 mg prednisone every other day

• Active treatment for nontuberculous mycobacterial (NTM) infection

• Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonicsaline,azithromycin,Tobramycin Inhalation solution (TOBI®), Cayston® within 8 weeksprior to randomization

• Unwilling to discontinue current oral vitamin and antioxidant supplementation (e.g.,AquADEKs®, another source of β-carotene, vitamin A, vitamin E ortocopherols,vitamins D or K, n-acetylcysteine, glutathione, CoQ10, otherover-the-counter antioxidant) for the duration of the study

• Use of vitamins (other than control vitamin) or antioxidants within 4 weeks prior torandomization

• Daily use of > 2 cans of Boost or Pulmocare dietary supplement formulas

• Known hypersensitivity to oral AquADEKs®

• For women of child bearing potential:

1. positive pregnancy test at Visit 1 or at Visit 2, or

2. lactating or

3. unwilling to practice a medically acceptable form of contraception (acceptableforms of contraception: abstinence, hormonal birth control, intrauterine device,or barrier method plus a spermicidal agent)

• Subject unlikely to complete the study as determined by the Investigator

• Any condition that the Investigator believes would interfere with the intent of thisstudy or would make participation not in the best interest of the subject

• Use of investigational therapies within 4 weeks prior to randomization

• Current tobacco smoker

• Current use of anticoagulant medications

• Severe malnutrition based either on having a BMI less than the 5th percentile forsubjects < 18 years of age or a body mass index (BMI) less than 18 kg/m2 for subjects > 18 years of age.

• Subjects with poorly controlled CF-related diabetes on active insulin therapy, definedas having a Glycosylated Hemoglobin (HgbA1c) ≥ 7.5% at the most recent historicevaluation of HgbA1c