A Single Dose Study to Assess the Safety, Effects, and Blood and Urine Drug Levels of AZD3293 in Healthy Subjects

Study Overview
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Brief Summary
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This is a single dose study in healthy male and female (of non-child bearing potential) volunteers, to assess the safety, effects on the body, and blood and urine drug levels of AZD3293. AZD3293 is being developed for the treatment of Alzheimer's Disease

Detailed Description
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 Including an Open-Label Food Effect Group in Healthy Male and Non-Fertile Female Volunteers

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

Conditions
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Healthy Young Volunteers, Healthy Elderly 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 male and female (of non-childbearing potential) subjects Body mass index (BMI) between 19 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg Exclusion Criteria: History or presence of psychiatric disease/condition, GI, renal, hepatic, cardiovascular, psychiatric, or retinal diseases or disorders History of neurological disease, including seizures, recent memory impairment, or clinically significant head injury History of 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

Ages Eligible for Study
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Minimum Age: 18 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>Up to 11 sequential cohorts of healthy young and healthy elderly subjects are planned, with single ascending doses ranging from 1mg to a maximum of 1000mg | 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 |
| --- | --- | --- |
| Adverse event monitoring. |  | From baseline up to 10 days. | 
| Assessment of vital signs and physical examination. | The vital signs of body temperature, blood pressure and pulse are going to be measured. | From baseline up to 10 days. | 
| Clinical laboratory tests: hematology. |  | From baseline up to 10 days. | 
| Clinical laboratory tests: urine analysis. |  | From baseline up to 10 days. | 
| Evaluation of 12-lead digital electrocardiogram (ECG). | QT/QTc interval, rhythm, rate, morphology is going to be measured. | From baseline up to 10 days. | 
| Assessment of telemetry. | As reported by investigator. | From baseline up to 10 days. | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) | Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline. | From baseline up to 10 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) in the terms of AUC, AUC(0-t), AUC(0-24). | Where (AUC(0-t)) is area under the plasma concentration-time curve from zero to the last measurable concentration and (AUC(0-24)) area under the plasma concentration-time curve from zero to 24 hours post-dose. | Up 4 days | 
| Investigation on the effect of AZD3293 on biomarkers relevant for Pharmacodynamics in plasma. | Biomarker PD Aβ (1-40, 1-42) parameters are: Maximum observed plasma concentration (Cmax) Time to Cmax (tmax) Minimum observed plasma concentration (Cmin) Minimum observed plasma concentration below the individual healthy volunteer baseline (pre-dose biomarker concentration prior to dosing) (ΔCmin) Time to Cmin (tmin) Duration (T) of concentration below individual healthy volunteer baseline (BBL), if appropriate for the data (tBBL) Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC(0-t)) Area under the plasma concentration-time curve from zero to 24 hours post dose (AUC(0-24)) Area under the plasma biomarker concentration curve from time zero to 24 hour that is below individual healthy volunteer baseline (ΔAUC(0-24)). | Up to 4 days. | 
| Investigation of the potential influence of food on Pharmacokinetics (PK) following a single dose of AZD3293. | Pharmacokinetics (PK) in the terms of plasma Cmax and AUC. | Up to 4 days. | 
| Investigation of the relationship between Pharmacokinetics (PK) and Pharmacodynamics (PD) of AZD3293. | The Pharmacokinetics (PK) variables may be plasma concentrations or summary measurements such as Cmax or AUC. The Pharmacodynamics (PD) variables may include biomarkers in plasma such as Aβ (1-40, 1-42) or exploratory PD biomarkers, or safety variables. | Up to 4 days. | 
| Pharmacokinetics assessment in the terms of fu (%) (fraction of unbound AZD3293 and AZ13569724 in plasma). |  | Up to 4 days. | 
| Pharmacokinetics in the terms of Cmax (Maximum observed plasma concentration) and tmax (Time to Cmax ). |  | Up to 4 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZD3293, Healthy volunteers, Elderly volunteers, Phase 1, Single Ascending Dose Study