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

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

Detailed Description
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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.

Official Title
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A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation First-Time-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of Single and Repeat Oral Doses of FDL169 in Healthy Volunteers

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: FDL169
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. Subjects who have history or presence of clinically significant cardiovascular, pulmonary, renal, hepatic, haematologic, gastrointestinal (endocrine or immunologic disease), at Screening. Donation of 500 mL or more blood within the previous 3 months. 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. Smoking or use tobacco products or substitutes equivalent to > 15 cigarettes/day. Any subject attempting to father a child within 3 months of their Follow-Up Visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo single dose<br>Placebo administered as a single dose | Drug: Placebo<br> <br> |
| Experimental: Single dose (Dose level 1)<br>FDL169 (Dose level 1) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 2)<br>FDL169 (Dose level 2) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 3)<br>FDL169 (Dose level 3) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 4)<br>FDL169 (Dose level 4) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 5)<br>FDL169 (Dose level 5) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 6)<br>FDL169 (Dose level 6) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 7)<br>FDL169 (Dose level 7) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Single dose (Dose level 8)<br>FDL169 (Dose level 8) administered as a single dose | Drug: FDL169<br> <br> |
| Experimental: Additional single dose 1<br>Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Additional single dose 2<br>Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Additional single dose 3<br>Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Additional single dose 4<br>Single dose of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Food effect - fasted<br>Single dose of FDL169 in fasted conditions | Drug: FDL169<br> <br> |
| Experimental: Food effect - fed<br>Single dose of FDL169 in fed conditions | Drug: FDL169<br> <br> |
| Placebo Comparator: Placebo - multiple dose<br>Repeat doses of placebo | Drug: Placebo<br> <br> |
| Experimental: Multiple dose - Dose level 1<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Multiple dose - Dose level 2<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Multiple dose - Dose level 3<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Multiple dose - Dose level 4<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Multiple dose - additional dose level 1<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |
| Experimental: Multiple dose - additional dose level 2<br>Repeat doses of FDL169 to be administered at a dose level to be determined (up to Dose level 8) | Drug: FDL169<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Vital signs, electrocardiogram (ECG), safety laboratory data and adverse events (AEs) | Multiple points from screening to follow-up (up to 28 days) | 
| Part 1B: food effect on the tolerability of FDL169 for 48 h following a single dose | Vital signs, ECG, safety laboratory data and AEs | Multiple points from screening to follow-up (up to 42 days) | 
| 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) | Vital signs, ECG, safety laboratory data and AEs | Multiple points from screening to follow-up (up to 42 days) | 
| Part 1B: food effect on the pharmacokinetics of FDL169 for 48 h following a single dose | Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated | Multiple points from pre-dose to 48 h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: pharmacokinetic profile for 48 h following single oral doses of FDL169 | Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated | Multiple points from pre-dose to 48 h post-dose | 
| Part 2: pharmacokinetic profile following multiple oral doses of FDL169 (assessed throughout dosing and for 24 h post-final dose) | Pharmacokinetic parameters: Cmax, tmax, lambdaz, t1/2, AUC(0-t), AUC(0-tau), AUC (0-inf) CL/F and AUC%extrapolated | Multiple points from pre-dose to 24 h post-dosing on Day 14 |