Bioavailability and Pharmacokinetics Study of FDL169 in Healthy Subjects and Subjects With Cystic Fibrosis

• ClinicalTrials.gov Identifier: NCT02767297
• Recruitment Status: Completed
• First Posted: May 10, 2016
• Last Update Posted: October 24, 2016
• Sponsor: Flatley Discovery Lab LLC
• Information provided by (Responsible Party): Flatley Discovery Lab LLC

Tracking Information

• First Submitted Date: May 5, 2016
• First Posted Date: May 10, 2016
• Last Update Posted Date: October 24, 2016
• Study Start Date: April 2016
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2016)

• Part 1: Maximum plasma concentration of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: Time to maximum plasma concentration of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: Individual estimate of the terminal elimination rate constant of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: Terminal half-life of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: AUC from the time of dosing to the time of the last observed concentration for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: AUC extrapolated to infinity from dosing time, based on the last observed concentration for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: Clearance of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 1: AUC% extrapolated for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 72 h post-dose ]
• Part 2: Maximum plasma concentration of FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: Time to maximum plasma concentration of FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: Individual estimate of the terminal elimination rate constant of FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: Terminal half-life of FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: AUC from the time of dosing to the time of the last observed concentration for FDL169 (and metabolites) following multiple oral doses FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: AUC extrapolated to infinity from dosing time, based on the last observed concentration for FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: Clearance of FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 2: AUC% extrapolated for FDL169 (and metabolites) following multiple oral doses of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post last dose ]
• Part 3: Maximum plasma concentration of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: Time to maximum plasma concentration of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: Individual estimate of the terminal elimination rate constant of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: Terminal half-life of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: AUC from the time of dosing to the time of the last observed concentration for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: AUC extrapolated to infinity from dosing time, based on the last observed concentration for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: Clearance of FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]
• Part 3: AUC% extrapolated for FDL169 (and metabolites) following single oral dose of FDL169 [ Time Frame: Multiple points from pre-dose to 48 h post-dose ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 9, 2016)

• Number of subjects with clinically significant changes in systolic and diastolic blood pressure following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects with clinically significant changes in heart rate following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects with clinically significant changes in oral temperature following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects with clinically significant changes in oxygen saturation following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects with clinically significant 12-lead ECG abnormalities following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects with abnormal laboratory values following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]
• Number of subjects experiencing treatment-related adverse events following single and multiple oral doses of FDL169 [ Time Frame: Multiple points from screening to follow-up (7 days after last dose) ]

Original Secondary Outcome Measures (submitted: May 6, 2016)

• Part 1: safety and tolerability of reference formulation and test formulation in healthy subjects for 72 h following single oral doses of FDL169 (Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs)) [ Time Frame: Multiple points from screening to follow-up (up to 35 days) ]
  Vital signs, ECG, safety laboratory data and AEs
• Part 2: safety and tolerability of test formulation in healthy subjects following multiple oral doses of FDL169 (Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs)) [ Time Frame: Multiple points from screening to follow-up (up to 24 days) ]
  Vital signs, ECG, safety laboratory data and AEs
• Part 3: safety and tolerability of test formulation in CF subjects for 48 h following single oral doses of FDL169 (Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs)) [ Time Frame: Multiple points from screening to follow-up (up to 21 days) ]
  Vital signs, ECG, safety laboratory data and AEs

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bioavailability and Pharmacokinetics Study of FDL169 in Healthy Subjects and Subjects With Cystic Fibrosis
• Official Title: A Three-Part Phase 1b Bioavailability and Pharmacokinetics Study of Two Formulations of FDL169 in Healthy Subjects and Subjects With Cystic Fibrosis
• Brief Summary: 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).

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label)
• Condition: Cystic Fibrosis
• Intervention: Drug: FDL169

Study Arms

• Experimental: Part 1: Single dose (cross over)
  FDL169 reference formulation and test formulation administered as a single dose in healthy subjects
  Intervention: Drug: FDL169
• Experimental: Part 2: Multiple dose (dose level 1)
  FDL169 test formulation (Dose level 1) administered as repeat doses in healthy subjects
  Intervention: Drug: FDL169
• Experimental: Part 2: Multiple dose (dose level 2)
  FDL169 test formulation (Dose level 2) administered as repeat doses in healthy subjects
  Intervention: Drug: FDL169
• Experimental: Part 2: Multiple dose (dose level 3)
  FDL169 test formulation (Dose level 3) administered as repeat doses in healthy subjects
  Intervention: Drug: FDL169
• Experimental: Part 3: Single dose
  FDL169 test formulation administered as a single dose in CF subjects
  Intervention: Drug: FDL169

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2016): 46
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2016
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02767297
• Other Study ID Numbers: FDL169-2015-03
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Flatley Discovery Lab LLC
• Study Sponsor: Flatley Discovery Lab LLC
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stuart Elborn, MD; Queen's University

• PRS Account: Flatley Discovery Lab LLC
• Verification Date: October 2016