Pharmacology study of GLPG3067- Pro/combination in healthy females
Research type
Research Study
Full title
A randomized, double-blind, placebo-controlled, single-center study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses for 14 days of GLPG3067-Pro and of the combination of GLPG3067-Pro, GLPG2222, and GLPG2737 for 14 days, including an open label, single-dose relative bioavailability and food effect part, in adult, healthy, female subjects
IRAS ID
247607
Contact name
David Bell
Contact email
Sponsor organisation
Galapagos NV
Eudract number
2018-000830-37
Duration of Study in the UK
0 years, 7 months, 26 days
Research summary
GLPG3067 is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator in clinical development for the treatment of subjects with cystic fibrosis (CF). GLPG3067 has relatively poor bioavailability (BA). In order to achieve the anticipated therapeutic exposures, 20 tablets (10 mm diameter round, 50-mg film-coated tablet) are currently required for a daily dose. To improve GLPG3067’s BA and reduce the pill burden for CF patients, a prodrug, GLPG3067-Pro, has been developed. \nGLPG3067-Pro (G1557203) is a valine ester of GLPG3067. Preclinical pharmacokinetic (PK) data in rat and dog after oral administration of GLPG3067-Pro showed the rapid cleavage of GLPG3067-Pro into GLPG3067, resulting in high systemic exposures of GLPG3067 and minimal GLPG3067-Pro plasma concentrations for a very short time after administration in the general circulation. Higher exposure of GLPG3067 and lower inter animal variability for GLPG3067 concentrations was also observed with GLPG3067-Pro when compared to GLPG3067.\nThe current study is a first-in-human (FIH), randomized, double-blind, placebo-controlled, dose-escalation study. This study design is regarded as being an appropriate approach to initiate the assessment of safety, tolerability, and pharmacokinetics (PK) of GLPG3067-Pro administered to healthy female subjects. Due to the narrow safety margin for testicular toxicity and the reasoning that healthy males would not elicit any benefit from this compound, the study is restricted to healthy females only.\nThe relative BA of GLPG3067-Pro given as a capsule will be compared to GLPG3067 given as film-coated tablets by characterizing the PK of GLPG3067. In addition, the effect of food after administration of GLPG3067-Pro will be evaluated by characterizing the PK of GLPG3067 under both fasted and fed conditions.\nIn addition, the safety, tolerability, and PK of GLPG3067-Pro administered together with GLPG2222 and GLPG2737, two other compounds in development for treatment of CF, will be evaluated. \nData from this study is intended to support replacing the current GLPG3067 formulation in future clinical studies.\n\n
REC name
HSC REC A
REC reference
18/NI/0088
Date of REC Opinion
19 Jun 2018
REC opinion
Further Information Favourable Opinion