A Two-part Single and Multiple Dose Study to Assess the Safety , Pharmacokinetics and Effects of AZD3293 in Healthy Japanese Young and Elderly Volunteers

Phase 1

Completed

Conditions: Healthy Japanese Young and Elderly Male and Non-fertile Female Volunteers

Brief Summary: This study consists of two parts, ie, single dose part with young healthy subjects (Part 1) and single and multiple dose part with elderly healthy subjects (Part 2), to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD3293 following single and multiple ascending dose administration to healthy subjects.

Detailed Description: This is a Phase I, randomised, double-blind, placebo-controlled, single centre study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD3293 following single and multiple ascending dose administration to healthy subjects. This study consists of two parts, ie, single dose part with young healthy subjects (Part 1) and single and multiple dose part with elderly healthy subjects (Part 2). The study design allows a gradual escalation of dosage levels between sequential cohorts with safety monitoring to ensure the safety of the healthy subjects.

Recruitment & Eligibility

Inclusion Criteria

Healthy Japanese elderly and young males and females (of non-childbearing potential)
Body mass index (BMI) between 17 and 27 kg/m2 and weigh at least 40 kg and no more than 100 kg

Exclusion Criteria

Psychiatric disease/condition, GI, renal, hepatic, cardiovascular, psychiatric, or retinal diseases or disorders
Use of antipsychotic drugs , or chronic use of antidepressant or anxiolytic drugs.
Frequent use (more than 2 days per week during the last 12 weeks) of tobacco or other nicotine products.
Neurological disease, including seizures, recent memory impairment, or clinically significant head injury.

Arm && Interventions

Group	Intervention	Description
AZD3293	AZD3293	AZD3293 will be administered as single dose of an oral solution in Part 1 and single and multiple doses of an oral solution in Part 2. The ascending doses are planned to be 15, 50 and 150 mg for young subjects in Part 1 and 15 and 50 mg for elderly subjects in Part 2. Before proceeding to next dose level, safety, tolerability and pharmacokinetic data from the previous cohort(s) will be evaluated by a Safety Review Committee. Part 2 will start after confirming safety and tolerability in Part 1.
Placebo	Placebo	Placebo given (2 subjects in each cohort)

Primary Outcome Measures

Name	Time	Method
Safety - Adverse Events	Day of first dose to follow up	Safety - Number of subjects reporting any adverse events during the study

Secondary Outcome Measures

Name	Time	Method
PK Cmax - Overall Study	0, 0.5,1,2,3,4,8,12,24,48 hr single dose, multiple dose does not include 48 hr	Pharmacokinetic maximum concentration
PK AUC - Overall Study (SAD & MAD Parts)	0,0.5,1,2,3,4,8,12,24,48 hr single dose, multiple dose does not include 48 hr	Pharmacokintic Area Under the Curve (0 to t)
Biomarker	Pre dose vs Day 14	Biomarker (Abeta 1-40; A beta 1-42) % change from baseline