Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial
Background: Idiopathic lung fibrosis (IPF) causes irreversible lack of breathing. Individuals with IPF have elevated concentrations of autotaxin in lung tissue and lysophosphatidic acidity (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is really a novel, potent, selective autotaxin inhibitor with higher dental exposure. We explored the results of GLPG1690 in patients with IPF.
Methods: It was a randomised, double-blind, placebo-controlled phase 2a study completed in 17 centres in Italia, Ukraine and also the United kingdom. Qualified patients were aged 4 decades or older, non-smokers, not implementing pirfenidone or nintedanib, coupled with a centrally confirmed proper diagnosis of IPF. We used a pc-generated randomisation schedule to assign patients 1:3 to get placebo or 600 mg dental GLPG1690 once daily for 12 days. The main outcomes were safety (adverse occasions), tolerability, pharmacokinetics, and pharmacodynamics. Spirometry was assessed like a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02738801.
Findings: Between March 24, 2016, and could 2, 2017, 72 patients were screened., who 49 were ineligible and 23 were signed up for eight centres (six in Ukraine and 2 within the United kingdom). Six patients were allotted to receive placebo and 17 to get GLPG1690. 20 patients completed the research after one out of each group stopped due to adverse occasions and something within the GLPG1690 group withdrew consent. Four (67%) patients within the placebo group and 11 (65%) within the GLPG1690 group had treatment-emergent adverse occasions, many of which were mild to moderate. The commonest occasions within the GLPG1690 group were infections and infestations (ten occasions) and respiratory system, thoracic, and mediastinal disorders (eight occasions) without any apparent variations in the placebo group. Two (12%) patients within the GLPG1690 group had occasions which were judged to become associated with treatment. Serious adverse occasions were observed in two patients within the placebo group (you a urinary system infection, acute kidney injuries, minimizing respiratory system infection and yet another had atrioventricular block, second degree) and something within the GLPG1690 group (cholangiocarcinoma that led to stopping of treatment). No patients died. The pharmacokinetic and pharmacodynamic profiles of GLPG1690 were much like individuals formerly proven in healthy controls. LPA C18:2 concentrations in plasma were consistently decreased. Mean vary from baseline in forced vital capacity at week 12 was 25 mL (95% CI -75 to 124) for GLPG1690 and -70 mL (-208 to 68 mL) for placebo.
Interpretation: Our findings support further growth and development of GLPG1690 like a novel strategy to IPF.