Study of GLPG1837 in Subjects With Cystic Fibrosis (G551D Mutation)
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: GLPG1837 dose 1Drug: GLPG1837 dose 2Drug: GLPG1837 dose 3
- Registration Number
- NCT02707562
- Lead Sponsor
- Galapagos NV
- Brief Summary
32 cystic fibrosis patients with the G551D mutation will be treated for 4 weeks, consisting of three consecutive treatment periods: two 1-week periods followed by one 2-week period, evaluating one dose of GLPG1837 each. After the treatment period, there is a 7-10 days follow-up period.
During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability).
Changes in sweat chloride will be assessed as biomarker from baseline onwards, and changes in pulmonary function (efficacy) will be explored throughout the study. The amount of GLPG1837 present in the blood (pharmacokinetics) will also be determined.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- Male or female subjects ≥ 18 years of age, with a confirmed diagnosis of cystic fibrosis
- Subjects with gating G551D CFTR mutation on at least one allele in the CFTR gene
- Subjects currently receiving treatment with ivacaftor on a stable regimen or not on a treatment regimen with ivacaftor, for at least 2 weeks prior to screening
- Weight ≥ 40.0 kg
- Subjects on stable concomitant treatment regimen for at least 4 weeks prior to baseline (excluding ivacaftor)
- Pre- or post-bronchodilator FEV1 ≥ 40% of predicted normal
- Subject will have to use highly effective contraceptive methods
- On an ivacaftor-containing treatment regimen and unable or unwilling to discontinue ivacaftor for the washout and treatment periods of the study
- Concomitant use of antifungal drugs within 4 weeks of baseline
- A history of a clinically meaningful unstable or uncontrolled chronic disease
- Liver cirrhosis and portal hypertension
- Any significant change in the medical regimen for pulmonary health within 4 weeks of baseline
- Unstable pulmonary status or respiratory tract infection or changes in therapy for pulmonary disease within 4 weeks of baseline
- Abnormal liver function
- Clinically significant abnormalities on ECG
- History of malignancy, solid organ/haematological transplantation
- Abnormal renal function
- Participation in another experimental therapy study within 30 days or 5 times halflife
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3 GLPG1837 dose 3 GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3 GLPG1837 dose 1 GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks GLPG1837 dose 1, GLPG1837 dose 2, GLPG1837 dose 3 GLPG1837 dose 2 GLPG1837 twice daily oral dosing - morning and evening, for 4 weeks
- Primary Outcome Measures
Name Time Method Changes in vital signs - composite outcome measure Up to 9 weeks To evaluate the safety and tolerability of GLPG1837 in terms of abnormal vital signs as measured by temperature, blood pressure, heart rate and respiratory rate, at every visit
Changes in adverse events Up to 9 weeks To evaluate the safety and tolerability of GLPG1837 in terms of adverse events at every visit
Changes in laboratory parameters Up to 7 weeks To evaluate the safety and tolerability of GLPG1837 in terms of abnormal laboratory parameters at every visit
Changes in electrocardiogram Up to 7 weeks To evaluate the safety and tolerability of GLPG1837 in terms of abnormal electrocardiogram at every visit
Changes in physical examination - composite outcome measure Up to 9 weeks To evaluate the safety and tolerability of GLPG1837 in terms of abnormalities during physical examination at every visit
- Secondary Outcome Measures
Name Time Method Changes in sweat chloride concentration Up to 9 weeks To evaluate the effect of GLPG1837 in terms of change in sweat chloride concentration, a biomarker to measure cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function at every visit
Changes in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry Up to 9 weeks To explore the effect of GLPG1837 in terms of change in pulmonary function (forced expiratory volume in 1 second, FEV1) assessed by spirometry at every visit
Plasma levels of GLPG1837: Cmax, the maximum observed plasma concentration Up to 3 weeks To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the Cmax, the maximum observed plasma concentration
Plasma levels of GLPG1837: tmax, the time of occurrence of Cmax Up to 3 weeks To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the tmax, the time of occurrence of Cmax
Plasma levels of GLPG1837: AUC, the area under the plasma concentration-time curve Up to 3 weeks To characterize the pharmacokinetics (PK) of GLPG1837 by measuring the amount in plasma between Day 8 and Day 29 at every visit; On Day 29, an 8-hour profile will determine the AUC, the area under the plasma concentration-time curve
Trial Locations
- Locations (16)
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
The Prince Charles Hospital
🇦🇺Chermside, Australia
Monash Medical Centre
🇦🇺Clayton, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czech Republic
Mater Adult Hospital
🇦🇺South Brisbane, Australia
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Uniklinik Carl-Gustav-Carus
🇩🇪Dresden, Germany
Lungenheilkunde München-Pasing
🇩🇪München, Germany
Beamont Hospital
🇮🇪Dublin, Ireland
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Liverpool Heart and Chest Hospital
🇬🇧Liverpool, United Kingdom
The Medicines Evaluation Unit Ltd
🇬🇧Manchester, United Kingdom
Universitätsklinkikum Koeln
🇩🇪Cologne, Germany
Royal Brompton Hospital
🇬🇧London, United Kingdom