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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Elderly Volunteers; Healthy Young Volunteers
• Intervention / Treatment: Drug: AZD3293; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD3293; 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; Oral solution
Placebo Comparator: Placebo; Placebo given (2 subjects in each cohort)	Drug: Placebo; Oral solution

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Robert C Alexander, MD, AstraZeneca; Principal Investigator: Ronald Goldwater, MD, Parexel

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimate): December 3, 2012

Study Record Updates

• Last Update Posted (Estimate): August 27, 2013
• Last Update Submitted That Met QC Criteria: August 26, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Healthy volunteers; Phase 1; AZD3293; Elderly volunteers; Single Ascending Dose Study
• Other Study ID Numbers: D5010C00001