A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)

Inclusion Criteria: * Males and females aged 18 to 65 years * Patients with diagnosis of CF as confirmed by at least one of the following: * Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR * Documented sweat sodium test ≥ 60 mmol/L OR * Abnormal nasal potential difference test OR * At least one well-characterized disease-causing genetic mutation in the CF transmembrane conductance regulatory (CFTR) gene AND * Accompanying symptoms characteristic of CF * Normal (or abnormal but not clinically significant) electrocardiogram (ECG) * Normal intraocular pressure (IOP) between 10 and 21 mm Hg at Screening. * Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate (HR) in the absence of any medications for hypertension; these will be measured after the subject has rested supine for 3 minutes; normal BP is taken to be 90 to 140 mm Hg systolic and 50 to 89 mm Hg diastolic; normal HR is taken to be 40 to 100 beats per minute (bpm) * Able to communicate well with the investigator and to comply with the requirements of the entire study * Provision of written informed consent to participate as shown by a signature on the volunteer consent form * Nonsmokers for at least 180 days (6 months) prior to Screening * Must be willing to abstain from alcohol and strenuous exercise during the 48 hours prior to Screening, 72 hours prior to initial dosing, and during the study * Forced expiratory volume in 1 second (FEV1) ≥ 50% predicted normal for age, gender, and height at Screening as per Knudson et al * Stable regimen of oral CF medications, dornase alfa, and physiotherapies for the period 28 days prior to Screening; those subjects taking continuous (non-cycling) inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to Screening * Subjects must be in the off-phase of any cyclical inhaled antibiotic treatment regimen * Must test negative for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) at Screening * Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom) during heterosexual intercourse from Day -1 through completion of the study and continuing for at least 90 days from date of last dose of study drug * Male subjects must refrain from sperm donation from Day -1 through completion of the study and continuing for at least 90 days from the date of last dose of study drug * Nonlactating females. Females on hormone replacement therapy (estrogen/progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 90 days prior to Screening * Females must have a negative serum gonadotropin pregnancy test at Screening and Day -1 * Nonpregnant females of childbearing potential must agree to use highly effective (\<1% failure rate) contraception during heterosexual intercourse from Screening, throughout the study, and for at least 30 days following the last dose of study drug * Glomerular filtration rate (GFR) of \< 60 mL/min/1.73m2 at Screening (GFR to be calculated using the Cockcroft-Gault equation), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3× upper limits of normal (ULN) * Chest radiograph at Screening without significant acute findings (e.g., infiltrates \[lobar or diffuse interstitial\], pleural effusion, pneumothorax); or chest radiograph, CT, or MRI obtained within the 90 days prior to Screening without acute findings or significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed. A chest radiograph obtained and interpreted between Screening and Day 1 is also acceptable for determining eligibility. Exclusion Criteria: * Administration of any investigational drug or device in the 28 days prior to Screening * A need for any new medication during the period 28 days before first dosing with study drug, except those deemed by the principal investigator/clinical investigator not to interfere with the outcome of the study * Subjects who routinely use inhaled hypertonic saline must discontinue use for at least 14 days prior to clinic admission and for the duration of the study * Use of trimethoprim or high dose ibuprofen (\> 800 mg/day) during the 28 days prior to first dosing * Serious adverse reaction or hypersensitivity to any drug * Existence of any surgical or medical condition which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism, or excretion of the drug * Lactating females * History of airway intolerance to hypertonic saline * History of lung transplantation * History of a positive test for Burkholderia cepacia * History of cirrhosis or ascites * History of clinically significant adrenal disease * History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) ≤ 40% * History of glaucoma * Consumption of drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) within 28 days (or 5 half-lives of inducing agent, whichever is longer) of Screening * Subjects requiring any of the following drugs in the 28 days prior to Screening: diuretics (e.g., spironolactone, amiloride, thiazide), ACE inhibitors, angiotensin receptor blockers, oral corticosteroids, or medicines for hypertension * Donation or loss of greater than 400 mL of blood in the period 90 days (3 months) prior to Screening * Major surgery within 180 days (6 months) of Screening * Hemoglobin levels \< 120 g/L in females or \< 130 g/L in males taken at Screening and at Day -1 * Serum potassium \> 5 mEq/L taken at Screening and at Day -1 * Poor venous access