Bioavailability and Pharmacokinetics Study of FDL169 in Healthy Subjects and Subjects With Cystic Fibrosis
Bioavailability and Pharmacokinetics Study of FDL169 in Healthy Subjects and Subjects With Cystic Fibrosis
To determine the relative bioavailability of the capsule (reference) and tablet (test)
 formulations of FDL169 in healthy adult males and females, and to evaluate the
 pharmacokinetic (PK) profile FDL169 tablets (test formulation) in both healthy adult males
 and females, and subjects with cystic fibrosis (CF).
This is a three-part study.

 Part 1:

 Part 1 of the study is a single dose, open-label, randomized crossover study in healthy male
 and female subjects to compare the relative bioavailability of two formulations of FDL169.

 Part 2:

 Part 2 of the study is a multiple, escalating dose study of three different doses of the test
 formulation of FDL169 in healthy male and female subjects to evaluate the PK profile of the
 test formulation of FDL169.

 Part 3:

 Part 3 of the study is a single dose, open-label study in male and female subjects with CF to
 determine the PK profile of the test formulation of FDL169.
Inclusion Criteria:

 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.

 Exclusion Criteria:

 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.