PET Study of Repeated ASN51 in Healthy Volunteers

This is a phase 1, open-label, dose escalation, PET study to investigate the brain occupancy of O-GlcNAcase, and the PD response in PBMCs, after repeated doses of ASN51 in healthy subjects.

Inclusion Criteria:Normotensive male volunteer (PET subjects)Male or female volunteer of non-childbearing potential (PBMC-only subjects)Deemed healthy on the basis of a clinical history, physical and neurological examination, ECG, vital signs, and laboratory tests of blood and urineAgree to follow the contraception requirements of the trialAble to give fully informed written consent.Exclusion Criteria:Significant (> 10%) recent weight changePositive tests for hepatitis B & C, HIVSevere adverse reaction to any drugSensitivity to trial medicationDrug or alcohol abuseRegular consumption of xanthine-containing productsFrequent use of nicotine-containing productsSevere adverse reaction to any drugSensitivity to trial medication (all subjects) or PET imaging radioligand (PET subjects)Use of over-the-counter medication (with the exception of paracetamol [acetaminophen]) during the 7 days before the first dose of radioligand (PET subjects) or trial medication (PBMC subjects) (or longer if the medicine is a potential enzyme inducer), or prescribed medication during the 28 days before first dose of radioligand (PET subjects) or trial medication (PBMC subjects)Received vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 2 weeks of screeningParticipation in other clinical trials of unlicensed medicinesLoss of more than 400 mL blood, within the 3 months before the first dose of tracer (PET subjects) or trial medication (PBMC subjects)Clinically relevant abnormal findings at the screening assessment, including ECG abnormalities (all subjects) or those identified by MRI scan (PET subjects only)Acute or chronic illnessClinically relevant abnormal history of or concurrent medical (including neurological or psychiatric) conditionPositive C-SSRS resultVeganPossibility that volunteer will not cooperateUnsatisfactory venous accessObjection by General Practitioner (GP)PET subjects only: significant exposure to research related radiation (more than 10 mSv) within the previous 12 monthsContraindications to arterial cannulation (eg Allen's test indicates risk) or MRI scanning (eg presence of a cardiac pacemaker or other implanted electronic device or a history of claustrophobia)