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.