A Study to Evaluate Safety, PK and PD of FDL169 in Cystic Fibrosis Subjects
- Registration Number
- NCT03093714
- Lead Sponsor
- Flatley Discovery Lab LLC
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Multiple dose placebo as repeat doses in CF subjects FDL 169 test formulation (Dose Level 1) FDL169 Multiple dose (Dose Level 1) FDL 169 test formulation administered as repeat doses in CF subjects FDL 169 test formulation ( Dose Level 3) FDL169 Multiple dose (Dose Level 3) FDL 169 test formulation administered as repeat doses in CF subjects FDL 169 test formulation (Dose Level 2) FDL169 Multiple dose (Dose Level 2) FDL 169 test formulation administered as repeat doses in CF subjects
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events 28 days Safety and tolerability of FDL169 as determined by the incidence of adverse events (AEs) and serious adverse events (SAEs).
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters, Cmax 28 days The pharmacokinetic parameters of FDL169: maximal plasma concentration (Cmax).
Pharmacokinetic parameters, AUC 28 days The pharmacokinetic parameters of FDL169: area under the plasma concentration curve (AUC).
Pharmacokinetic parameters, CL/F 28 days The pharmacokinetic parameters of FDL169: clearance (CL/F).
Pharmacokinetic parameters, Tmax 28 days The pharmacokinetic parameters of FDL169: maximal concentration (Tmax).
Pharmacokinetic parameters, V/F 28 days The pharmacokinetic parameters of FDL169: apparent volume of distribution (V/F).
Trial Locations
- Locations (13)
Mater Misericordiae Ltd
🇦🇺South Brisbane, Queenland, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Charité - Universitätsmedizin Berlin CVK
🇩🇪Berlin, Germany
FN v Motole, Pediatrická klinika, Centrum cystické fibrózy
🇨🇿Praha, Czechia
Klinik Donaustauf, Zentrum für Pneumologie
🇩🇪Donaustauf, Germany
Ruhrlandklinik
🇩🇪Essen, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
NICRN Respiratory Research Office, Belfast City Hospital
🇬🇧Belfast, United Kingdom
Research Dept., Liverpool Heart and Chest Hospital
🇬🇧Liverpool, United Kingdom
The Medicines Evaluation Unit (MEU)
🇬🇧Manchester, United Kingdom
NIHR Wellcome Trust Clinical Research Facility
🇬🇧Southampton, United Kingdom
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Royal Brompton Hospital
🇬🇧London, United Kingdom