Patient description: The patient is a 55 year old man visiting his primary care physician for lower urinary tract symptoms including frequency, urgency, weak stream, incomplete emptying and intermittent flow for the past 9 months. Further evaluation revealed: IPSS score : 15 Post-void residual: 70 mL Prostate volume (TRUS): 60 mL Prostate-specific antigen (PSA) level: 3.2 ng/mL 10 mL/sec of maximum flow rate when urine volume was 130 mL He is otherwise healthy only using Vit D 1000 units daily. His recent blood chemistry (3 days ago) was normal: Hgb: 13.5 g/dl WBC: 135000 /mm3 Plt: 350000 /ml PT: 11 second PTT: 35 second INR: 0.9 Creatinine: 0.5 mg/dl BUN: 10 mg/dl U/A: Color: yellow Appearance: cloudy PH: 5.3 Specific gravity: 1.010 Glc: 100 Nitrite: negative Ketone: none Leukocyte esterase: negative RBC: negative WBC: 2 WBCs/hpf U/C: negative

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Cystic Fibrosis Parts 1 and 2: 1. Healthy, males and females between 18 and 55 years of age, inclusive, with a BMI of >19 and <30 kg/m2. 2. If sexually active, must meet the contraception requirements. Part 3: 1. Male and female subjects aged 18 years and older. 2. If sexually active, must meet the contraception requirements. 3. Diagnosis of CF. 4. History of pancreatic insufficiency. 5. Forced expiratory volume in 1 second (FEV1) ≥40% of predicted normal for age, sex and height at screening  Parts 1 and 2: 1. Prior or ongoing medical condition, medical history, physical findings, ECG findings or laboratory abnormality that could adversely affect the safety of the subject. 2. Alkaline phosphatase, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level >1.5 x upper limit of normal (ULN) at screening. 3. Use of prescription or non-prescription drugs within 21 days or five half-lives (whichever is longer) before the first dose of study medication, unless the medication will not interfere with the study procedures or compromise subject safety. 4. Pregnant or nursing females. 5. Serum creatinine or total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%). 6. History of prolonged QT and/or QTcF interval. 7. ECG with a single QTcF >450 msec in males, >460 msec in females, at Screening. 8. Positive urinary drugs of abuse screen at Screening or Day -1, or positive alcohol screen at Day -1. 9. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units. 10. History of human immunodeficiency virus (HIV) or positive HIV, hepatitis B or hepatitis C results at screening. 11. Donation of 500 mL or more blood within 3 months before Day -1. 12. Participation in a clinical trial involving receipt of an investigational product within the past 90 days or exposure to more than four new chemical entities with 12 months of the first dosing day. 13. Current smoking or use of tobacco products or substitutes. Former smokers will be eligible, provided they have not smoked for at least 6 months before Day -1. 14. Use of any prescription and non-prescription medications that are inhibitors or inducers of cytochrome P450 (CYP) 3A4 within 7 days before Day -1. Part 3: 1. History of any illness, or ongoing acute illness that could impact the safety of the subject or confound study results. 2. Abnormal liver function ≥3 x ULN: AST, ALT, total bilirubin. 3. A pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks prior to the Baseline (Day 1) Visit 4. Use of herbal and dietary supplements within 21 days or five half-lives (whichever is longer) before the first dose of study medication, unless the medication will not interfere with the study procedures or compromise subject safety. 5. Pregnant or nursing females. 6. Serum creatinine or total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%). 7. History of prolonged QT and/or QTcF interval. 8. ECG with a single QTcF >450 msec in males, >460 msec in females, at Screening. 9. Positive urinary drugs of abuse screen at Screening or Day -1, or positive alcohol screen at Day -1. 10. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units. 11. History of HIV, or positive HIV, hepatitis B or hepatitis C results at screening. 12. Donation of 500 mL or more blood within 3 months before Day -1. 13. Participation in a clinical trial involving receipt of an investigational product within the past 90 days or exposure to more than four new chemical entities with 12 months of the first dosing day. 14. Current smoking or use of tobacco products or substitutes. Former smokers will be eligible, provided they have not smoked for at least 6 months before Day -1. 15. Use of any prescription and non-prescription medications that are inhibitors or inducers of CYP3A4, within 7 days before Day -1