A Phase 1 clinical trial to assess the safety, tolerability and pharmacokinetics of PBT434 in healthy volunteers.

INTERVENTION: PBT434 is supplied as 50mg and 200 mg immediate release oral capsules. The dose in the single ascending dose (SAD) phase range between 50‐1600 mg total daily dose, given as a single dose. The dose in the multiple ascending dose (MAD) phase ranges between 200‐800 mg total daily dose, given twice daily for Days 1‐7, and once daily on Day 8. The doses in the SAD phase are : 50 mg, 100 mg, 300 mg, 900mg, 1200 mg and 1600mg. The Total Daily Doses (TDD) in the MAD phase are 200mg, 400 mg and 800mg. The proposed doses will be confirmed based on the safety and PK data generated from the SAD portion of the study. Participants do not take part in both the SAD and MAD phases. The phases are independently randomised. In both the SAD and MAD phases, hand and mouth checks will be performed after each dose to assure that IP has been swallowed by the subject. The approximate length of time between the SAD and MAD phases is 8 weeks. CONDITION: Atypical Parkinsonism Idiopathic Parkinson's Disease PRIMARY OUTCOME: To evaluate the safety and tolerability of PBT434 after single and multiple oral dose administration by measuring adverse events (AEs), Physical examination, Vital signs, Safety 12‐lead Electrocardiograms (ECGs) and Clinical laboratory values ; SECONDARY OUTCOME: To determine the pharmacokinetics (PK) of PBT434 (and potential metabolites) after single and multiple dose administration; by measuring plasma the following PK parameters: ; ; • AUC(0‐t) ; • AUC(inf) ; • %AUCextrap ; • Cmax ; • tmax ; • t½ ; • Vz/F ; • CL/F (parent only) ; • Apparent terminal elimination rate constant ; ; To evaluate the pharmacokinetics of PBT434 (and potential metabolites) after multiple oral dose administration in healthy elderly subjects by measurement of the following plasma PK parameters: ; ; • AUC ; • Cmax ; • Cmin ; • Cavg ; • Tmax ; • t½ ; • PTF% (Percent Fluctuation) ; • Accumulation index (Cmax SS/Cmax FD) ; • Accumulation index (AUCSS/AUCFD) ; ; To evaluate the preliminary effect of food on the pharmacokinetics of PBT434 (and potential metabolites) after single dose administration by measuring the following plasma PK parameters: ; ; • AUC(0‐t) ; • AUC(inf) ; • %AUCextrap ; • Cmax ; • tmax ; • t½ ; • Vz/F ; • CL/F (parent only) ; • Apparent terminal elimination rate constant ; INCLUSION CRITERIA: SAD and MAD phases require healthy male and female (not of childbearing potential) adult volunteers aged between 18 and 55 (n=78 total in this age group). One cohort of the MAD phase will be conducted in healthy elderly participants. The elderly cohort in MAD will be comprised of healthy male and female (not of childbearing potential) volunteers aged greater than or equal to 65 years (n=10 participants in this age group).