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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 in Healthy Japanese Male and Non-Fertile Female Volunteers Including Elderly

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

Intervention / Treatment
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* Drug: AZD3293
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3293<br>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. | Drug: AZD3293<br>* Oral solution<br>|
| Placebo Comparator: Placebo<br>Placebo given (2 subjects in each cohort) | Drug: Placebo<br>* Oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Adverse Events | Safety - Number of subjects reporting any adverse events during the study | Day of first dose to follow up | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZD3293, Healthy volunteers, Young volunteers, Elderly volunteers, Japanese volunteers, Phase 1, Single and multiple ascending dose study