Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis
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.
Interventions
DRUGFDL169
CFTR corrector
DRUGPlacebo
Placebo for FDL169
Sponsors
Flatley Discovery Lab LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters, Cmax | 28 days | The pharmacokinetic parameters of FDL169: maximal plasma concentration (Cmax). |
| Pharmacokinetic parameters, Tmax | 28 days | The pharmacokinetic parameters of FDL169: maximal concentration (Tmax). |
| 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, V/F | 28 days | The pharmacokinetic parameters of FDL169: apparent volume of distribution (V/F). |
Countries
Australia, Czechia, Germany, United Kingdom
Outcome results
None listed