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

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

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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG116Js
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males or non-pregnant, non-lactating healthy females
2. Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
3. Must agree to follow the study's contraception requirement Subject has normal healthy oral mucosa with no clinically significant findings

Exclusion Criteria:

1. Subjects who have received any IMP in a clinical research study within the previous 3 months
2. Subjects who have previously received FDL169
3. History of any drug or alcohol abuse in the past 2 years
4. 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)
5. Current smokers and those who have smoked within the last 12 months
6. 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)
7. Alkaline phosphatase, aspartate aminotransferase and/or alanine aminotransferase level >1.5 x upper limit of normal at screening
8. Abnormal renal function at screening, defined as estimated glomerular filtration rate <60 mL/min using the Modification of Diet in Renal Disease (MDRD) equation
9. Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in)
10. Positive drugs of abuse test result
11. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
12. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
13. Subjects with a history of abdominal surgery eg cholecystectomy (appendectomy is allowed unless procedure was within 12 months)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Flatley Discovery Lab LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): January 15, 2018
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 2, 2018
• Last Update Submitted That Met QC Criteria: November 1, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Cystic Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: FDL169-2017-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No