Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis

Exclusion Criteria

• •1. History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the investigator
• •2. Prolonged QT interval with Fridericia's correction \>450 msec at screening
• •3. Abnormal liver function as defined by aspartate transaminase (AST), alanine transaminase (ALT), or bilirubin \>1.5× the upper limit of the normal range
• •4. Abnormal renal function at screening defined as creatinine clearance \<90 mL/min using the Cockroft-Gault equation
• •5. Clinically significant screening results that would exclude subject from the study (e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by the investigator
• •6. Participation in another clinical study or treatment with an investigational agent within 30 days or five half-lives, whichever is longer, prior to Study Day 1
• •7. History of cancer within the past 5 years (excluding non-melanoma skin cancer)
• •8. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
• •9. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine \[urine cotinine is the detection mechanism for nicotine\], opiates, barbiturates, amphetamines, and benzodiazepines) or positive alcohol test at screening
• •10. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb)
• •11. Clinically significant infection within 3 months of screening as determined by the investigator
• •12. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof
• •13. Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion
• •14. Pregnant or nursing women
• •15. Any conditions that, in the opinion of the investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study
• •16. Use of prohibited medications within 14 days prior to dosing of study drug
• •1. Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
• •2. History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
• •3. History of organ transplantation
• •4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
• •5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
• •6. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
• •7. Pregnant or nursing women
• •8. Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
• •1. Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
• •2. History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
• •3. History of organ transplantation
• •4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 28 days of Day 1
• •5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days of Day 1
• •6. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
• •7. Pregnant or nursing women
• •8. Currently taking or has taken a CFTR modulator within 14 days prior to the screening visit