Safety, pharmacokinetics and pharmacodynamics of HTL0009936, a selective muscarinic M1 -acetylcholine receptor agonist: A randomized cross-over trial.
Charlotte BakkerSamantha PrinsJan LiptrotEllen P HartErica S KlaassenGiles A BrownAlastair BrownMiles CongreveMalcolm WeirFiona H MarshallJasper StevensDavid M CrossTim TaskerPradeep J NathanGeert Jan GroeneveldPublished in: British journal of clinical pharmacology (2021)
HTL0009936 showed well-characterized pharmacokinetics and single doses were safe and generally well-tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement.