Abstract
ABSTRACT
Background
Linaprazan glurate (LG), a potassium‐competitive acid blocker (PCAB), has shown up to 100% and 93% 4‐week healing rates in a Phase 2 study in patients with LA grade A/B and C/D erosive oesophagitis, respectively.
Aim
To assess the Pharmacodynamic (PD) effect and Pharmacokinetics (PK) of multiple‐dose administration of LG.
Methods
In the open, randomised, parallel‐group, Phase 1 study, PD (intragastric pH) and PK were investigated after the first dose and 14 days of repeated administration of LG at dose levels 25, 50 and 75 mg q. d. and 25, 50 and 75 mg b.d.
Results
A total of 73 subjects were treated with LG during the study. After the first LG dose, pH > 4 was achieved within 60 and 10 min for the 50 mg b.d. and 75 mg b.d. dose groups, respectively. Dose–response was observed for HTRs at pH > 4, with > 90% for 50 mg b.d. and 75 mg b.d. on Day 1 and > 95% on Day 14. HTR was higher with 25 mg b.d. than with 50 mg q. d. both on Day 1 and Day 14. Mean AUC and mean C
max
for linaprazan, the main LG metabolite, increased approximately in proportion to dose with no apparent accumulation.
Conclusions
LG provided a rapid increase in gastric pH after the first dose, with an HTR pH > 4 close to 100% for dose levels 50 mg b.d. and 75 mg b.d. Linaprazan AUC and C
max
increased in proportion to LG dose. LG was safe and well tolerated at the studied dose levels.