A Study to Evaluate Safety, PK and PD of FDL169 in Cystic Fibrosis Subjects

Cystic Fibrosis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate Safety, Pharmacokinetics (PK) and Pharmacodynamics(PD) of FDL169 in Cystic Fibrosis (CF) Subjects Homozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093714
• Other study ID #: FDL169-2015-04
• Status: Completed
• Phase: Phase 1
• First received: March 16, 2017
• Last updated: April 11, 2018
• Start date: August 23, 2017
• Est. completion date: April 3, 2018

Study information

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

Clinical Trial Summary

This is a multicenter, randomized, placebo-controlled, dose-escalation study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF.

Description:

This is a multicenter, randomized double-blind, placebo-controlled dose-escalation and parallel-arm, dose-ranging study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF who are homozygous for the F508del-CFTR mutation will be enrolled in two cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 3, 2018
• Est. primary completion date: April 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Male or female subjects with a confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis or two CF-causing mutations,documented in the subject's medical record or confirmed at screening.

• Age 18 and above on the date of informed consent.

• Weight =40 kg.

• Homozygous for the F508del-CFTR mutation. Genotyping to be confirmed at screening.

• Ability to perform a valid, reproducible spirometry test with demonstration of a forced expiratory volume in 1 sec (FEV1) >40% of predicted normal for age, sex and height.

• Screening laboratory tests with no clinically significant abnormalities that would interfere with the study assessments (as judged by the Investigator).

• Subjects who are sexually active must agree to follow the study's contraception requirements.

Exclusion Criteria:

• An acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks prior to Day 1.

• Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening.

• Impaired renal function or known portal hypertension.

• History of prolonged QT and/or QTcF (Fridericia's correction) interval (>450 msec) or QTcF >450 msec at Screening.

• History of solid organ or hematological transplantation.

• History of alcohol abuse or drug addiction (including cannabis, cocaine and opiates) during the past year, (as judged by the Investigator).

• Use of ivacaftor or lumacaftor, within 4 weeks of Day 1

• Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to Day 1.

• Ongoing immunosuppressive therapy (including systemic corticosteroids).

• Hemoglobin <10 g/dL.

• Abnormal liver function, at screening.

• Abnormal renal function at screening.

• Ongoing participation in another clinical study or prior participation without appropriate washout (minimum of 10 half- lives or 30 days, whichever is longer) prior to Screening visit.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• FDL169
CFTR corrector
• Placebo
Placebo for FDL169

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	The Alfred Hospital	Melbourne
Australia	Mater Misericordiae Ltd	South Brisbane	Queenland
Czechia	FN v Motole, Pediatrická klinika, Centrum cystické fibrózy	Brno
Czechia	FN v Motole, Pediatrická klinika, Centrum cystické fibrózy	Praha
Germany	Charité - Universitätsmedizin Berlin CVK	Berlin
Germany	Klinik Donaustauf, Zentrum für Pneumologie	Donaustauf
Germany	Ruhrlandklinik	Essen
Germany	Universitätsklinikum Frankfurt	Frankfurt
United Kingdom	NICRN Respiratory Research Office, Belfast City Hospital	Belfast
United Kingdom	Research Dept., Liverpool Heart and Chest Hospital	Liverpool
United Kingdom	Royal Brompton Hospital	London
United Kingdom	The Medicines Evaluation Unit (MEU)	Manchester
United Kingdom	NIHR Wellcome Trust Clinical Research Facility	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Flatley Discovery Lab LLC

Countries where clinical trial is conducted

Australia,  Czechia,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events	Safety and tolerability of FDL169 as determined by the incidence of adverse events (AEs) and serious adverse events (SAEs).	28 days
Secondary	Pharmacokinetic parameters, Cmax	The pharmacokinetic parameters of FDL169: maximal plasma concentration (Cmax).	28 days
Secondary	Pharmacokinetic parameters, Tmax	The pharmacokinetic parameters of FDL169: maximal concentration (Tmax).	28 days
Secondary	Pharmacokinetic parameters, AUC	The pharmacokinetic parameters of FDL169: area under the plasma concentration curve (AUC).	28 days
Secondary	Pharmacokinetic parameters, CL/F	The pharmacokinetic parameters of FDL169: clearance (CL/F).	28 days
Secondary	Pharmacokinetic parameters, V/F	The pharmacokinetic parameters of FDL169: apparent volume of distribution (V/F).	28 days