GSK2798745

07/01/2021 - "An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough. "
07/01/2021 - "Final study results for posterior median cough counts showed a 34% (90% credible interval: -3%, +85%) numerical increase for GSK2798745 compared to placebo. "
07/01/2021 - "This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. "

06/01/2019 - "GSK2798745 was well-tolerated in healthy volunteers and patients with stable heart failure. "
06/01/2019 - "No significant safety issues or serious adverse events were observed with GSK2798745 in healthy volunteers and patients with heart failure. "
06/01/2019 - "Two cohorts of subjects with mild to moderate heart failure were also administered GSK2798745 once daily for up to 7 days. "
01/01/2021 - "As such, TRPV4 blocker GSK2798745 was recently investigated in phase I/IIa trials to reduce pulmonary edema caused by heart failure (HF). "
01/01/2021 - "SIGNIFICANCE STATEMENT: In the absence of a suitable target engagement biomarker, we developed an ex vivo assay to predict the pharmacological activity of the transient receptor potential vanilloid 4 (TRPV4) blocker GSK2798745 in healthy volunteers and subjects with heart failure (HF) from phase I/IIa trials. "

01/01/2021 - "The potency values from the ex vivo assay were consistent with those predicted from a rat in vivo pharmacokinetic/pharmacodynamic model of pulmonary edema, strongly suggesting that circulating levels of GSK2798745 were sufficient to robustly block TRPV4, supporting use of GSK2798745 for assessing efficacy in HF."
01/01/2021 - "Using matched GSK2798745 plasma levels, a pharmacokinetic/pharmacodynamic (PK/PD) relationship was calculated as 2.9 nM IC50, consistent with the 6.5 nM IC50 of GSK2798745 obtained from a rat in vivo PK/PD model of pulmonary edema after correcting for rat-to-human differences. "
01/01/2021 - "As such, TRPV4 blocker GSK2798745 was recently investigated in phase I/IIa trials to reduce pulmonary edema caused by heart failure (HF). "
08/08/2019 - "GSK2798745, a clinical candidate, was identified as an inhibitor of the transient receptor potential vanilloid 4 (TRPV4) ion channel for the treatment of pulmonary edema associated with congestive heart failure. "

09/09/2021 - "GSK2798745, an antagonist of the transient receptor potential vanilloid 4 (TRPV4) ion channel, was recently investigated in clinical trials for the treatment of cardiac and respiratory diseases. "

10/01/2020 - "We performed a Phase I, placebo-controlled, double-blind, randomized, parallel group, proof-of-mechanism study to investigate the effects of TRPV4 channel blocker, GSK2798745, on pulmonary-vascular barrier permeability using a model of lipopolysaccharide (LPS)-induced lung inflammation. "