Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial

Maher, Toby M.; Aar, E. M. Van Der; Steen, Olivier Van de; Allamassey, Lisa; Desrivot, Julie; Dupont, Sonia; Fagard, Liesbeth; Ford, Paul; Fieuw, Ann; Wuyts, Wim

doi:10.1016/s2213-2600(18)30181-4

Cited by 202 publications

(167 citation statements)

References 22 publications

Supporting

Mentioning

161

Contrasting

Order By: Relevance

“…Plasma exposure to GLPG1690 increased with increasing dose with minimal deviation from dose proportionality following single and multiple doses. Overall, the PK profile of GLPG1690 was similar to that reported in patients with IPF treated with GLPG1690 capsules (600 mg once daily) …”

Section: Discussionsupporting

confidence: 75%

“…GLPG1690 is a first‐in‐class autotaxin inhibitor currently being investigated as a novel therapy for IPF . This first‐in‐human study demonstrated that GLPG1690 was well tolerated after administration of single doses up to 1500 mg and multiple doses up to 1000 mg once daily for 14 days.…”

Section: Discussionmentioning

confidence: 83%

“…In preclinical studies, GLPG1690 has demonstrated efficacy in a mouse bleomycin‐induced pulmonary fibrosis model (therapeutic setting): GLPG1690 was superior to pirfenidone and similar to nintedanib in reducing the Ashcroft fibrotic score and collagen content . Furthermore, a recent phase 2a study (FLORA study) in 23 patients with IPF demonstrated that GLPG1690 was well tolerated, reduced plasma LPA C18:2 levels, and stabilized forced vital capacity (FVC) after 12 weeks of treatment …”

mentioning

confidence: 99%

See 2 more Smart Citations

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials

Aar

Desrivot

Dupont

et al. 2019

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

GLPG1690 is a novel autotaxin inhibitor in development for the treatment of idiopathic pulmonary fibrosis (IPF). We report phase 1 studies investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG1690 in healthy subjects. We performed a first‐in‐human randomized, double‐blind, placebo‐controlled trial of single (20, 60, 150, 300, 600, 1000, 1500 mg) and multiple (14 days: 150 mg twice daily; 600 and 1000 mg once daily) ascending oral doses of GLPG1690 (NCT02179502), and a randomized, open‐label, crossover relative bioavailability study to compare the PK of tablet and capsule formulations of GLPG1690 600 mg and to assess the effect of food on PK of the tablet formulation (NCT03143712). Forty and 13 subjects were randomized in the first‐in‐human and relative bioavailability studies, respectively. GLPG1690 was well tolerated, with no dose‐limiting toxicity at all single and multiple doses. GLPG1690 was rapidly absorbed and eliminated, with a median tmax and mean t1/2 of approximately 2 and 5 hours, respectively. GLPG1690 exposure increased with increasing dose (mean Cmax, 0.09‐19.01 µg/mL; mean AUC0‐inf, 0.501‐168 µg·h/mL, following single doses of GLPG1690 20‐1500 mg). PD response, evidenced by rapid reduction in plasma lysophosphatidic acid (LPA) C18:2 levels, increased with increasing GLPG1690 plasma levels, plateauing at approximately 80% reduction in LPA C18:2 at around 0.6 µg/mL GLPG1690. Tablet and capsule formulations had similar PK profiles, and no clinically significant food effect was observed when comparing tablets taken in fed and fasted states. The safety, tolerability, and PK/PD profiles of GLPG1690 support continued clinical development for IPF.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 99%

See 1 more Smart Citation

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials

Aar

Desrivot

Dupont

et al. 2019

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…New agents targeting the various stages in the pathogenesis (Figure ) of disease are under study in IPF and include calpain inhibitors, which are calcium‐dependent cysteine proteases that influence cell signalling; metformin, which activates AMP‐activated protein kinase facilitating deactivation and apoptosis of myofibroblasts potentially reversing established fibrosis; and GLPG1690, a novel inhibitor of autotaxin, an enzyme involved in lysophosphatidic acid (LPA) production. A phase 2a randomised placebo‐controlled trial with GLPG1690 showed favorable stability of FVC (although not sufficiently powered) compared to placebo with good safety profile . BMS‐986020, an LPA receptor antagonist, has demonstrated a slower rate of FVC decline in a recent Phase 2 double‐blinded randomised control trial .…”

Section: Future Directionmentioning

confidence: 99%

Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges

2019

View full text Add to dashboard Cite

Interstitial lung disease (ILD) encompasses a large group of pulmonary conditions sharing common clinical, radiological and histopathological features as a consequence of fibrosis of the lung interstitium. The majority of ILDs are idiopathic in nature with possible genetic predisposition, but is also well recognised as a complication of connective tissue disease or with certain environmental, occupational or drug exposures. In recent years, a concerted international effort has been made to standardise the diagnostic criteria in ILD subtypes, formalise multidisciplinary pathways and standardise treatment recommendations. In this review, we discuss some of the current challenges around ILD diagnostics, the role of serological testing, especially, in light of the new classification of Interstitial Pneumonia with Autoimmune Features (IPAF) and discuss the evidence for therapies targeted at idiopathic and immune‐related pulmonary fibrosis.

show abstract

“…These brilliant results raised the hope for finding a definitive cure for IPF and paved the way for newer studies exploring the effectiveness of different molecules. Some of them, such as human recombinant pentraxin 2, PBI‐4050 and GLPG1690, showed promising results in phase 2 studies. Currently, the research landscape is highly flourishing.…”

Section: Disclosure Statementmentioning

confidence: 99%

Twenty‐five years of Respirology: Advances in idiopathic pulmonary fibrosis

2019

View full text Add to dashboard Cite

Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial

Abstract: Galapagos.

Cited by 202 publications

References 22 publications

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials

Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges

Twenty‐five years of Respirology: Advances in idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About