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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01739647
First received: November 30, 2012
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Healthy Young Volunteers
Healthy Elderly Volunteers
Drug: AZD3293
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Adverse event monitoring. [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
  • Assessment of vital signs and physical examination. [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
    The vital signs of body temperature, blood pressure and pulse are going to be measured.

  • Clinical laboratory tests: hematology. [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
  • Clinical laboratory tests: urine analysis. [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
  • Evaluation of 12-lead digital electrocardiogram (ECG). [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
    QT/QTc interval, rhythm, rate, morphology is going to be measured.

  • Assessment of telemetry. [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
    As reported by investigator.

  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From baseline up to 10 days. ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacokinetics (PK) in the terms of AUC, AUC(0-t), AUC(0-24). [ Time Frame: Up 4 days ] [ Designated as safety issue: No ]
    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.

  • Investigation on the effect of AZD3293 on biomarkers relevant for Pharmacodynamics in plasma. [ Time Frame: Up to 4 days. ] [ Designated as safety issue: No ]

    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)).

  • Investigation of the potential influence of food on Pharmacokinetics (PK) following a single dose of AZD3293. [ Time Frame: Up to 4 days. ] [ Designated as safety issue: No ]
    Pharmacokinetics (PK) in the terms of plasma Cmax and AUC.

  • Investigation of the relationship between Pharmacokinetics (PK) and Pharmacodynamics (PD) of AZD3293. [ Time Frame: Up to 4 days. ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetics assessment in the terms of fu (%) (fraction of unbound AZD3293 and AZ13569724 in plasma). [ Time Frame: Up to 4 days. ] [ Designated as safety issue: No ]
  • Pharmacokinetics in the terms of Cmax (Maximum observed plasma concentration) and tmax (Time to Cmax ). [ Time Frame: Up to 4 days. ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: December 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739647

Locations
United States, Maryland
Research Site
Baltimore, Maryland, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Robert C Alexander, MD AstraZeneca
Principal Investigator: Ronald Goldwater, MD PAREXEL Early Phase Clinical Unit
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01739647     History of Changes
Other Study ID Numbers: D5010C00001
Study First Received: November 30, 2012
Last Updated: August 26, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by AstraZeneca:
AZD3293
Healthy volunteers
Elderly volunteers
Phase 1
Single Ascending Dose Study

ClinicalTrials.gov processed this record on August 21, 2014