Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H₄ receptor inhibitor SENS-111 using a modified caloric test in healthy subjects.

ABSTRACT:

Aim

A Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H₄ receptor antagonist SENS-111, an oral small molecule.

Methods

One hundred healthy subjects were randomized in a placebo-controlled, double-blind study evaluating single-ascending doses (SAD; 100-500 mg) and multiple-ascending doses (MAD; 50-150 mg day^-1 , 4 days; 200-250 mg day^-1 , 7 days). Effects of SENS-111 on nystagmus and vertigo induced by modified caloric tests were measured in the MAD studies. Population PK and PK/PD models were developed using a nonlinear mixed-effects approach.

Results

SENS-111 was well tolerated with mild to moderate events. No sedation was reported. A maximal tolerated dose was

SUBMITTER: Venail F 

PROVIDER: S-EPMC6255991 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature