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FTIH - Single and Repeat Oral Doses of FDL169 in Healthy Volunteers

Phase 1
Completed
Conditions
Cystic Fibrosis
Interventions
Drug: Placebo
Registration Number
NCT02359357
Lead Sponsor
Flatley Discovery Lab LLC
Brief Summary

To determine the safety and tolerability of single and multiple escalating doses of FDL169 in healthy male subjects.

Detailed Description

This study is the first time in human study and consists of two parts.

Part 1A:

Part 1 of the study is a randomised, double-blind, placebo-controlled, dose-escalation, first-time-in-human study to assess the safety, tolerability and PK profiles following single oral administrations of FDL169 to healthy male volunteers. Sixty-four (64) male subjects (8 per cohort) will be included in Part 1 of the study. Up to eight dose levels of FDL169 are planned to be tested in Part 1 of the study.

Part 1B:

Open label. Following completion of Part 1A of the study, an additional cohort of 8 subjects will receive a single dose of FDL169 in both fasted and fed states

Part 2:

Part 2 of the study is a randomised, double-blind, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK profiles following multiple oral administrations of FDL169 to healthy male subjects. Forty-eight male subjects, in cohorts of twelve, will be included in Part 2 of the study. It is planned to test up to four dose levels of FDL169 in Part 2.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
130
Inclusion Criteria

Healthy male subjects aged 18 to 45 years who fulfil standard safety screening assessments for the study (haematology/biochemistry, urinalysis, 12-lead electrocardiogram (ECG), vital signs and oral temperature) and who in the opinion of the Investigator, are medically suitable to participate in the study. Male subjects and their partners 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.

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 history or presence of clinically significant cardiovascular, pulmonary, renal, hepatic, haematologic, gastrointestinal (endocrine or immunologic disease), at Screening.
  3. Donation of 500 mL or more blood within the previous 3 months.
  4. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 21 days (or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Flatley Discovery Labs Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  5. Smoking or use tobacco products or substitutes equivalent to > 15 cigarettes/day.
  6. Any subject attempting to father a child within 3 months of their Follow-Up Visit.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo single dosePlaceboPlacebo administered as a single dose
Single dose (Dose level 8)FDL169FDL169 (Dose level 8) administered as a single dose
Additional single dose 1FDL169Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Additional single dose 2FDL169Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Food effect - fedFDL169Single dose of FDL169 in fed conditions
Multiple dose - Dose level 3FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Multiple dose - additional dose level 2FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Single dose (Dose level 1)FDL169FDL169 (Dose level 1) administered as a single dose
Single dose (Dose level 5)FDL169FDL169 (Dose level 5) administered as a single dose
Additional single dose 3FDL169Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Food effect - fastedFDL169Single dose of FDL169 in fasted conditions
Single dose (Dose level 4)FDL169FDL169 (Dose level 4) administered as a single dose
Single dose (Dose level 3)FDL169FDL169 (Dose level 3) administered as a single dose
Placebo - multiple dosePlaceboRepeat doses of placebo
Multiple dose - Dose level 2FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Single dose (Dose level 2)FDL169FDL169 (Dose level 2) administered as a single dose
Multiple dose - additional dose level 1FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Multiple dose - Dose level 1FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Multiple dose - Dose level 4FDL169Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Additional single dose 4FDL169Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8)
Single dose (Dose level 6)FDL169FDL169 (Dose level 6) administered as a single dose
Single dose (Dose level 7)FDL169FDL169 (Dose level 7) administered as a single dose
Primary Outcome Measures
NameTimeMethod
Part 1B: food effect on the tolerability of FDL169 for 48 h following a single doseMultiple points from screening to follow-up (up to 42 days)

Vital signs, ECG, safety laboratory data and AEs

Part 2: safety and tolerability following multiple oral doses of FDL169 (assessed throughout dosing and for 24 h post-final dose) (Vital signs, ECG, safety laboratory data and AEs)Multiple points from screening to follow-up (up to 42 days)

Vital signs, ECG, safety laboratory data and AEs

Part 1A: safety and tolerability for 48 h following single oral doses of FDL169 (Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs)Multiple points from screening to follow-up (up to 28 days)

Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs)

Part 1B: food effect on the pharmacokinetics of FDL169 for 48 h following a single doseMultiple points from pre-dose to 48 h post-dose

Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated

Secondary Outcome Measures
NameTimeMethod
Part 1: pharmacokinetic profile for 48 h following single oral doses of FDL169Multiple points from pre-dose to 48 h post-dose

Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated

Part 2: pharmacokinetic profile following multiple oral doses of FDL169 (assessed throughout dosing and for 24 h post-final dose)Multiple points from pre-dose to 24 h post-dosing on Day 14

Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated

Trial Locations

Locations (1)

Simbec Research Ltd

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Merthyr Tydfil, Wales, United Kingdom

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