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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03424252
• Other study ID #: FDL169-2017-05
• Status: Completed
• Phase: Phase 1
• Start date: December 18, 2017
• Est. completion date: January 15, 2018

Study information

• Verified date: February 2018
• Source: Flatley Discovery Lab LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: January 15, 2018
• Est. primary completion date: January 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• FDL169
Cystic Fibrosis Transmembrane Regulator (CFTR) corrector

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Flatley Discovery Lab LLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameters, Cmax	The pharmacokinetic parameters of FDL169; maximal plasma concentration (Cmax)	7 weeks
Primary	Pharmacokinetic parameters, Tmax	The pharmacokinetic parameters of FDL169; maximal concentration (Tmax)	7 weeks
Primary	Pharmacokinetic parameters, AUC	The pharmacokinetic parameters of FDL169; area under the plasma concentration curve (AUC)	7 weeks
Primary	Pharmacokinetic parameters, CL/F	The pharmacokinetic parameters of FDL169; clearance (CL/F)	7 weeks
Primary	Pharmacokinetic parameters, V/F	The pharmacokinetic parameters of FDL169; apparent volume of distribution (V/F)	7 weeks
Primary	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	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