Assessment of safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of the combination of GLPG2451 and GLPG2222, with or without GLPG2737, in adult subjects with cystic fibrosis
- Conditions
- genetic diseasethick mucus disease10083624
- Registration Number
- NL-OMON46421
- Lead Sponsor
- Galapagos NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
* Female or male subject *18 years of age, on the day of signing the ICF;* Confirmed clinical diagnosis of CF (documented in the subject*s medical record). ;* Eligible CFTR genotype at screening:;- Cohort A: Homozygous for the F508del CFTR mutation;- Cohort B: Heterozygous for the F508del CFTR mutation with a potentiator non-responsive mutation on the second allele;- Cohort C: Homozygous for the F508del CFTR mutation;* A body weight of *40 kg at screening. ;* Stable concomitant medication for pulmonary health for CF for at least 4 weeks prior to the first study drug administration and planned continuation of the same concomitant medication for the duration of the dosing period of the study. Subjects with diabetes mellitus and/or pancreatic insufficiency are eligible for the study provided they are on stable treatment (e.g. medication, diet, pancreatic enzyme replacement therapy) for at least 4 weeks prior to the first study drug administration in the opinion of the investigator.;* Forced expiratory volume in 1 second (FEV1): 40% * FEV1 * 90% of predicted normal for age, sex, and height at screening (pre- or post-bronchodilator) at screening. ;* Sweat chloride concentration *60 mmol/L at screening.;* Non-smoker and non-user of any nicotine and or cannabis containing products. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening. A non-user is defined as an individual who has abstained from any nicotine containing products for at least 1 year prior to the screening.;Reference is made to the protocol for a complete overview of the inclusion criteria.
* History of or ongoing allergic bronchopulmonary aspergillosis.;* Medical history of cataract (or lens opacity) and/or glaucoma.;* Cataract (or lens opacity) and/or glaucoma determined by an ophthalmologist during the screening period.;* Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.;* History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.;* Need for supplemental oxygen during the day, and >2 L/minute while sleeping.;* History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices).;* History of malignancy within the past 5 years (except for basal cell carcinoma of the skin with no evidence of recurrence and/or carcinoma in situ of the cervix that has been treated with no evidence of recurrence).;* Use of any moderate and strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeks prior to the first study drug administration (e.g., clarithromycin, itraconazole, ketoconazole, telithromycin, rifampin, carbamazepine).;* Use of CFTR modulator therapy (e.g., lumacaftor and/or ivacaftor) within 4 weeks prior to the first study drug administration.;* Use of any oral corticosteroid within 3 months of screening; or history of oral corticosteroid use for *30 days (cumulative) within 2 years of screening.;* Abnormal liver function test at screening; defined as AST and/or ALT and/or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) *3× the upper limit of normal (ULN); and/or total bilirubin *1.5× the ULN.;Reference is made to the protocol for a complete overview of the exclusion criteria.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Parts 1 & 2<br /><br>* Safety and tolerability, assessed by the number of subjects with AEs<br /><br>* Determine PK parameters (including Cmax, AUC0-24 on Day 14 and 28 (Part 1<br /><br>only) and Ctrough through 28 days) of GLPG2737, its active metabolite G1125498<br /><br>(M4), GLPG2451, its active metabolite G1171564 (M31) and GLPG2222<br /><br><br /><br>Part 2 only<br /><br>* Change from baseline in sweat chloride concentration at Day 28<br /><br>* Changes from baseline in percent predicted FEV1 at Day 28</p><br>
- Secondary Outcome Measures
Name Time Method <p>Key secondary endpoints Part 1 only<br /><br>* Change from baseline in sweat chloride concentration at Day 28<br /><br>* Changes from baseline in percent predicted FEV1 at Day 28<br /><br>Other secondary endpoints<br /><br>* Change from baseline in sweat chloride concentration at Day 15<br /><br>* Changes from baseline in percent predicted FEV1 at Day 15<br /><br>* Change from baseline (pre-dose on Day 1) in the respiratory domain of the<br /><br>cystic fibrosis questionnaire-revised (CFQ-R) on Day 28</p><br>