A Phase I, Open-Label, Single-Center Study to Assess the Absorption, Metabolism, and Excretion of [14C]-AZD3293 (AZD3293hADME)

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

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)

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Mass Balance Study
• Intervention / Treatment: Drug: AZD3293

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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;

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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;

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD3293; 7 subjects will receive AZD3293	Drug: AZD3293; 7 subjects will receive AZD3293

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 28, 2014
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimate): April 30, 2014

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: June 13, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Alzheimer disease; Beta secretase inhibitor
• Other Study ID Numbers: D5010C00007; AZD3293 hADME (Other Identifier: AstraZeneca)