A Phase I, Open-Label, Single-Center Study to Assess the Absorption, Metabolism, and Excretion of [14C]-AZD3293

Study Overview
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Brief Summary
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This study will be an open-label, non-randomized, absorption, metabolism, and excretion study to evaluate the mass balance, metabolite profiles, and rates and routes of elimination of [14C]-AZD3293 and derived metabolites following administration as a single 100-mg (containing approximately 150 µCi) oral dose (as an oral solution)

Detailed Description
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This study will be an open-label, non-randomized,absorption, metabolism, and excretion study to evaluate the mass balance, metabolite profiles, and rates and routes of elimination of [14C]-AZD3293 and derived metabolites following administration as a single 100-mg (containing approximately 150 µCi) oral dose (as an oral solution) following at least an 8-hour fast from food (not including water). Seven healthy male subjects will be enrolled in the study at a single study site to complete a minimum of 6 subjects. The study will consist of 2 visits.

Official Title
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A Phase I, Open-Label, Single-Center Study to Assess the Absorption, Metabolism, and Excretion After Oral Administration of [14C]-AZD3293 to Healthy Male Subjects

Conditions
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Healthy Volunteers, Mass Balance Study

Intervention / Treatment
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* Drug: AZD3293


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between 18 and 55 years of age, inclusive, at the time of consent with suitable veins for cannulation or repeated venipuncture; 2) Body weight between 50 to 100 kg, inclusive; 3) Within BMI range 19 to 30 kg/m2, inclusive; 4) In good health, as determined by no clinically significant findings from medical history, physical examination with neurological examination, 12-lead ECG, and vital signs as judged by the Investigator; - Exclusion Criteria: Participation in any prior study of AZD3293 or previous enrollment in the present study; 2) Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, interfere with absorption, distribution, metabolism or excretion of drugs, or influence the results or the subject's ability to participate in the study; 3) History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator; -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Health Services Research
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3293<br>7 subjects will receive AZD3293 | Drug: AZD3293<br>* 7 subjects will receive AZD3293<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters measured by assessment of AUC over time and Maximum observed concentration (Cmax) | Maximum observed concentration (Cmax) parameters will be calculated, for AZD3293, its metabolite; and [14C]-AZD3293-derived total radioactivity. | Up to Day 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments including vital sign measurements, ECGs, physical examinations, clinical laboratory evaluations, and a record of adverse events (AEs). | Safety assessments including vital sign measurements, ECGs, physical examinations, clinical laboratory evaluations, and a record of adverse events (AEs), will be performed before and following investigational product administration. | Up to Day 25 | 
| The Columbia-Suicide Severity Rating Scale (C-SSRS) | The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to assess the psychiatric health of subjects. | Up to day 25 | 
| Time to maximum observed concentration (tmax) | Time to maximum observed concentration (tmax) will be calculated for AZD3293 and its metabolite; and [14C]-AZD3293-derived total radioactivity. | Up to day 25 | 
| Area under the concentration-time curve | Area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0-t), will be calculated for AZD3293 and its metabolite ; and [14C]-AZD3293-derived total radioactivity concentrations. | Up to day 25 | 
| Area under the concentration-time curve extrapolated to infinity (AUC0-∞) | Area under the concentration-time curve extrapolated to infinity (AUC0-∞), apparent terminal elimination rate constant (λZ), will be calculated for AZD3293 and its metabolite ; and [14C]-AZD3293-derived total radioactivity. | Up to day 25 | 
| Apparent terminal elimination half-life (t1/2) | Apparent terminal elimination half-life (t1/2), will be calculated for AZD3293 and its metabolite; and [14C]-AZD3293-derived total radioactivity. | Up to day 25 | 
| Apparent oral clearance (CL/F) | Apparent oral clearance (CL/F) (AZD3293 only), will be calculated for AZD3293 concentrations. | Up to day 25 | 
| Apparent volume of distribution (Vz/F) | Apparent volume of distribution (Vz/F) (AZD3293 only) will be calculated for AZD3293 concentrations. | Up to day 25 | 
| Ratios for AUC0- | Ratios for AUC0- including the ratio of total radioactivity in whole blood/plasma; and the ratio of AZD3293 in plasma and total radioactivity in plasma, will be calculated. | Up to day 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta secretase inhibitor, Alzheimer disease