Inclusion Criteria:
- Healthy male subjects, 18 to 50 years of age, inclusive.
- Non-smokers or abstinence from tobacco for at least 3 months prior to screening.
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, with a minimum weight of 50 kg and maximum of 100 kg.
- Venous access sufficient to allow blood sampling as per the protocol.
- Agree to abstain from alcohol intake 24h before each administration of study drug, during the in-patient period of the study and 24 hours prior to all other out-patient clinic visits.
- Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site.
- In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the clinical study protocol restrictions and requirements.
- Subjects and their partners of childbearing potential must be willing to use 2 methods of contraception, one of which must be a barrier method, for the duration of the study and up to 90 days after the last dose.
Specifically, Part B/PET related inclusion criteria:
- Adequate arterial circulation in both hands (Allen's test).
- MRI scan without clinically significant abnormalities.
Specifically, Part C/FE related inclusion criteria:
- Subjects are not vegetarian and willing to eat a standardized high fat breakfast including butter and bacon.
Exclusion Criteria:
- History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal (GI), hepatic, or renal disorder.
- Positive Hepatitis B surface antigen (HBs Ag), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
- Use of any medications (prescription or over-the-counter (OTC)), vitamin, mineral, herbal, and dietary supplements (including grapefruit products) within 7 days of study drug administration, or less than 5 half-lives (whichever is longer).
- Have an estimated Glomerular Filtration Rate (eGFR) <80 mL/min/1.73m2.
Any of the following findings in the resting ECG:
- QTcF> 450 or < 300 msec at screening or baseline visit,
- Notable resting bradycardia (HR < 40 bpm) or tachycardia (HR > 100 bpm) at screening or baseline visit,
- Personal or family history of congenital long QT syndrome or sudden death,
- Screening or baseline ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g. neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves),
- Evidence of atrial fibrillation, atrial flutter, Left Bundle Branch Block (LBBB), Wolf-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit (note: a first degree heart block with PR not exceeding 250 msec can be allowed).
Specifically, Part B/PET related exclusion criteria:
- Previous inclusion in a research study and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as International Commission on Radiological Protection (ICRP) category IIb or above: no more than 1 mSv in addition to the natural background radiation in the previous 12 months including the dose from the study).
- Subject who fulfils any of the MRI contraindications on the standard radiography screening questionnaire (including the presence of ferromagnetic metal in the body or heart pacemaker).
- History of or suffers from claustrophobia or feels that they will be unable to lie still on their back in the PET camera for a period of 2 hours.
- Any known allergy to local anaesthetics or heparin.