An Phase 1 Study to Evaluate the Pharmacokinetic (PK) Profile of FDL169 New Formulations in Healthy Subjects

Study Overview
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Brief Summary
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Two parts, two periods, crossover study with part 2 is optional. In both parts, subjects will be randomized to sequentially receive both sublingual and oral formulations of FDL169.

Detailed Description
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This is a single center, open label study on healthy volunteers. The study will consist of up to 2 parts; the decision to proceed to the optional second part will be made following review of Part 1 data. Part 1 and optional Part 2 have randomized, 2 period crossover designs. Subjects will randomized to 1 of 2 treatment sequences in order to receive 2 single doses of FDL169 on separate occasions, one as a sublingual administration and one as an oral administration. There will be a minimum washout period of 10 days between FDL169 administrations. The duration of each part is approximately 7 weeks from screening to follow up.

Official Title
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A Phase 1, Open-label, Crossover, Randomised Study to Evaluate the Pharmacokinetic Profile of FDL169 Sublingual Formulations in the Fed State in Healthy Subjects

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: FDL169


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or non-pregnant, non-lactating healthy females Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator Must agree to follow the study's contraception requirement Subject has normal healthy oral mucosa with no clinically significant findings Exclusion Criteria: Subjects who have received any IMP in a clinical research study within the previous 3 months Subjects who have previously received FDL169 History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Current smokers and those who have smoked within the last 12 months Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative urine pregnancy test at screening and each admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration >40 mIU/mL) Alkaline phosphatase, aspartate aminotransferase and/or alanine aminotransferase level >1.5 x upper limit of normal at screening Abnormal renal function at screening, defined as estimated glomerular filtration rate <60 mL/min using the Modification of Diet in Renal Disease (MDRD) equation Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in) Positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator Subjects with a history of abdominal surgery eg cholecystectomy (appendectomy is allowed unless procedure was within 12 months)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDL169 Dose Level 1,sublingual to oral<br>Dose level 1 sublingual first and oral second. | Drug: FDL169<br>* Cystic Fibrosis Transmembrane Regulator (CFTR) corrector<br>|
| Experimental: FDL169 Dose Level 1 dosing,oral to sublingual<br>Dose level 1 oral first and sublingual second. | Drug: FDL169<br>* Cystic Fibrosis Transmembrane Regulator (CFTR) corrector<br>|
| Experimental: FDL169 Dose Level 2 sublingual to oral,Optional<br>Dose level 2 sublingual first and oral second. | Drug: FDL169<br>* Cystic Fibrosis Transmembrane Regulator (CFTR) corrector<br>|
| Experimental: FDL169 Dose Level 2 oral to sublingual,Optional<br>Dose level 2 oral first and sublingual second. | Drug: FDL169<br>* Cystic Fibrosis Transmembrane Regulator (CFTR) corrector<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters, Cmax | The pharmacokinetic parameters of FDL169; maximal plasma concentration (Cmax) | 7 weeks | 
| Pharmacokinetic parameters, Tmax | The pharmacokinetic parameters of FDL169; maximal concentration (Tmax) | 7 weeks | 
| Pharmacokinetic parameters, AUC | The pharmacokinetic parameters of FDL169; area under the plasma concentration curve (AUC) | 7 weeks | 
| Pharmacokinetic parameters, CL/F | The pharmacokinetic parameters of FDL169; clearance (CL/F) | 7 weeks | 
| Pharmacokinetic parameters, V/F | The pharmacokinetic parameters of FDL169; apparent volume of distribution (V/F) | 7 weeks | 
| Ratio of pharmacokinetic parameters, AUC, between sublingual and oral formulation | The pharmacokinetic parameters of FDL169; area under the plasma concentration curve (AUC) of FDL169 and its M1 metabolite following sublingual dosing compared to oral dosing | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Safety and tolerability of FDL169 as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s. | 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis