Pharmacokinetics of FDL169 in Healthy Female Subjects

A Phase I Dose Escalation Study to Assess the Pharmacokinetics (PK) of FDL169 in Healthy Female Volunteers

To determine the pharmacokinetics of single and multiple doses of FDL169 in healthy female subjects.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: FDL169

Detailed Description

This is a two-part study.

Part 1:

Part 1 of the study is a single-dose, dose-escalation, study to assess the safety, tolerability and PK profiles following oral administrations of FDL169 to healthy female volunteers in the fed state. Up to five doses will be assessed.

Part 2:

Part 2 of the study is a multiple-dose study to assess the safety, tolerability and PK profiles following oral administrations of FDL169 to healthy female volunteers in the fed state.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Wales
    • Merthyr Tydfil, Wales, United Kingdom, CF48 4DR
      • Simbec Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy female subjects aged 18 to 55 years inclusive and of any ethnic origin with a body mass index (BMI) of > 19 and < 30 kg/m2. Body Mass Index = Body weight (kg) / [Height (m)]
2. Subjects must be willing to use an effective method of contraception from first dose of investigational medicinal product (IMP) and for 3 months after the last dose of IMP (unless they are of non-child bearing potential).

Exclusion Criteria:

1. Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months.
2. Subjects who have any renal or clinically significant cardiac, renal or hepatic disease at Screening.
3. Subjects who have history or presence of clinically significant cardiovascular, pulmonary, renal, hepatic, haematologic, gastrointestinal (with the exception of Gilbert's syndrome or asymptomatic gallstones), endocrine or immunologic disease at Screening.
4. Have an abnormal twelve-lead ECG or an ECG with abnormality considered to be clinically significant in the opinion of the Investigator or an ECG with a single QTcB > 450 mSec.
5. Subjects with a positive urinary drugs of abuse screen or positive alcohol screen at Screening or Day -1.
6. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 21 units.
7. Subject with history of HIV or positive human immunodeficiency virus, hepatitis B or hepatitis C results.
8. Donation of 500 mL or more of blood within the previous 3 months.
9. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and FDL Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
10. Smoking or use of tobacco products or substitutes equivalent to > 15 cigarettes/day.
11. Any subject who is pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose (Dose level 1); FDL169 (Dose level 1) administered as a single dose	Drug: FDL169
Experimental: Single dose (Dose level 2); FDL169 (Dose level 2) administered as a single dose	Drug: FDL169
Experimental: Single dose (Dose level 3); FDL169 (Dose level 3) administered as a single dose	Drug: FDL169
Experimental: Single dose (Dose level 4); FDL169 (Dose level 4) administered as a single dose	Drug: FDL169
Experimental: Single dose (Dose level 5); FDL169 (Dose level 5) administered as a single dose	Drug: FDL169
Experimental: Multiple dose; Repeat doses of FDL169 to be administered at a dose level to be determined	Drug: FDL169

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Maximum plasma concentration of FDL169 (and metabolites) over 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dose
Part 1: Time to maximum plasma concentration of FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: Individual estimate of the terminal elimination rate constant of FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: Terminal half-life of FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: AUC from the time of dosing to the time of the last observed concentration for FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: AUC extrapolated to infinity from dosing time, based on the last observed concentration for FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: Clearance of FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 1: AUC% extrapolated for FDL169 (and metabolites) during 48 h following single oral doses of FDL169	Multiple points from pre-dose to 48 h post-dosing on Day 7
Part 2: Maximum plasma concentration of FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: Time to maximum plasma concentration of FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: Individual estimate of the terminal elimination rate constant of FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: Terminal half-life of FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final 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 of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final 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 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: AUC from the time of dosing to time t at steady state for FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: Clearance of FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose
Part 2: AUC% extrapolated for FDL169 (and metabolites) following multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post-final dose)	Multiple points from pre-dose to 48 h post-final dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with clinically significant changes in systolic blood pressure following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with clinically significant changes in diastolic blood pressure following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with clinically significant changes in pulse rate following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with clinically significant changes in oxygen saturation following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with clinically significant changes in oral temperature following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with clinically significant 12-lead ECG abnormalities following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients with abnormal laboratory values following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose
Number of patients experiencing treatment-related adverse events following single and multiple oral doses of FDL169 (assessed throughout dosing and for 48 h post (final) dose)	Multiple points from pre-dose to 48 h post (last) dose

Collaborators and Investigators

• Sponsor: Flatley Discovery Lab LLC
• Investigators: Principal Investigator: Khalid Abou-Farha, MBChB MD PhD, Simbec Research

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: February 2, 2016
• First Submitted That Met QC Criteria: February 8, 2016
• First Posted (Estimate): February 11, 2016

Study Record Updates

• Last Update Posted (Estimate): March 31, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: FDL169-2015-02