Healthy Volunteers, Mass Balance Study
Conditions
Keywords
Beta secretase inhibitor, Alzheimer disease
Brief summary
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
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.
Interventions
DRUGAZD3293
7 subjects will receive AZD3293
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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; \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters measured by assessment of AUC over time and Maximum observed concentration (Cmax) | Up to Day 25 | Maximum observed concentration (Cmax) parameters will be calculated, for AZD3293, its metabolite; and \[14C\]-AZD3293-derived total radioactivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to day 25 | The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to assess the psychiatric health of subjects. |
| Time to maximum observed concentration (tmax) | Up to day 25 | Time to maximum observed concentration (tmax) will be calculated for AZD3293 and its metabolite; and \[14C\]-AZD3293-derived total radioactivity. |
| Area under the concentration-time curve | Up to day 25 | 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. |
| Area under the concentration-time curve extrapolated to infinity (AUC0-∞) | Up to day 25 | 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. |
| Safety assessments including vital sign measurements, ECGs, physical examinations, clinical laboratory evaluations, and a record of adverse events (AEs). | Up to Day 25 | 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. |
| Apparent oral clearance (CL/F) | Up to day 25 | Apparent oral clearance (CL/F) (AZD3293 only), will be calculated for AZD3293 concentrations. |
| Apparent volume of distribution (Vz/F) | Up to day 25 | Apparent volume of distribution (Vz/F) (AZD3293 only) will be calculated for AZD3293 concentrations. |
| Ratios for AUC0- | Up to day 25 | 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. |
| Apparent terminal elimination half-life (t1/2) | Up to day 25 | Apparent terminal elimination half-life (t1/2), will be calculated for AZD3293 and its metabolite; and \[14C\]-AZD3293-derived total radioactivity. |
Countries
United States
Outcome results
None listed