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

• ClinicalTrials.gov Identifier: NCT03424252
• Recruitment Status: Completed
• First Posted: February 6, 2018
• Last Update Posted: November 2, 2018
• Sponsor: Flatley Discovery Lab LLC
• Information provided by (Responsible Party): Flatley Discovery Lab LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: FDL169	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Crossover, Randomised Study to Evaluate the Pharmacokinetic Profile of FDL169 Sublingual Formulations in the Fed State in Healthy Subjects
• Actual Study Start Date: December 18, 2017
• Actual Primary Completion Date: January 15, 2018
• Actual Study Completion Date: January 15, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetic parameters, Cmax [ Time Frame: 7 weeks ]
   The pharmacokinetic parameters of FDL169; maximal plasma concentration (Cmax)
2. Pharmacokinetic parameters, Tmax [ Time Frame: 7 weeks ]
   The pharmacokinetic parameters of FDL169; maximal concentration (Tmax)
3. Pharmacokinetic parameters, AUC [ Time Frame: 7 weeks ]
   The pharmacokinetic parameters of FDL169; area under the plasma concentration curve (AUC)
4. Pharmacokinetic parameters, CL/F [ Time Frame: 7 weeks ]
   The pharmacokinetic parameters of FDL169; clearance (CL/F)
5. Pharmacokinetic parameters, V/F [ Time Frame: 7 weeks ]
   The pharmacokinetic parameters of FDL169; apparent volume of distribution (V/F)
6. Ratio of pharmacokinetic parameters, AUC, between sublingual and oral formulation [ Time Frame: 7 weeks ]
   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

Secondary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 7 weeks ]
   Safety and tolerability of FDL169 as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

United Kingdom

Quotient Sciences

Nottingham, United Kingdom, NG116JS

Sponsors and Collaborators

Flatley Discovery Lab LLC

More Information

• Responsible Party: Flatley Discovery Lab LLC
• ClinicalTrials.gov Identifier: NCT03424252
• Other Study ID Numbers: FDL169-2017-05
• First Posted: February 6, 2018
• Last Update Posted: November 2, 2018
• Last Verified: February 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Flatley Discovery Lab LLC:

Cystic Fibrosis

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases