A Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer's Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01795339
First received: February 18, 2013
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

This is a two-part multiple dose study in healthy male and female (of non-child bearing potential) elderly volunteers, and in Alzheimer's disease patients, to assess the safety, effects on the body, and blood, CSF, and urine drug levels of AZD3293. AZD3293 is being developed for the treatment of Alzheimer's Disease


Condition Intervention Phase
Healthy Elderly Volunteers
Mild-to-moderate Alzheimer's Disease Patients
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, Two-Part, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 in Plasma and Cerebrospinal Fluid in Healthy Male and Non-Fertile Female Elderly Volunteers and in Mild-to-Moderate Alzheimer Disease Patients

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Adverse event monitoring [ Time Frame: From Baseline up to 20 days ] [ Designated as safety issue: Yes ]
  • Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams [ Time Frame: From Baseline up to 20 days ] [ Designated as safety issue: Yes ]
  • Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety) [ Time Frame: From Baseline up to 20 days ] [ Designated as safety issue: Yes ]
  • Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval [ Time Frame: Fron Baseline up to 20 days ] [ Designated as safety issue: Yes ]
  • Assessment of telemetry, as reported by Investigator Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From Baseline up to 20 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:
  • Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD) [ Time Frame: Up to 17 days ] [ Designated as safety issue: No ]
  • Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD) in mild-moderate AD patients in comparison to elderly healthy volunteers [ Time Frame: Up to 17 days ] [ Designated as safety issue: No ]
  • Investigation of the multiple dose Pharmacokinetics for AZD3293 and its metabolite AZ13569724, including dose proportionality for AZD3293 following oral administration [ Time Frame: Up 17 days ] [ Designated as safety issue: No ]
  • Investigation of the Pharmacokinetics/Pharmacodynamics relationship of the effect of AZD3293 on biomarkers relevant for Alzheimer Disease (AD) in plasma [ Time Frame: Up to 17 days ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: March 2013
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD3293
Part 1: Up to 6 sequential cohorts of healthy elderly subjects are planned, with multiple ascending doses, starting with 5 mg (subject to confirmation by the Safety Review Committee) Part 2: Up to 16 mild-to-moderate AD patients administered one to up to 3 dosage levels of AZD3293
Drug: AZD3293
Oral solution
Placebo Comparator: Placebo
Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)
Drug: Placebo
Oral solution

Detailed Description:

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Two-Part, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 in Plasma and Cerebrospinal Fluid in Healthy Male and Non-Fertile Female Elderly Volunteers and in Mild-to-Moderate Alzheimer Disease Patients

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Part 1: Healthy elderly male and female (of non-childbearing potential) subjects.
  • Part 2: Male and non-fertile female AD patients.
  • Body mass index (BMI) between 19 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg.
  • Part 2: Clinical diagnosis of probable AD according to the NINCDS-ADRDA criteria.
  • Part 2: Manifestation of AD symptoms at least 6 months before randomization.

Exclusion Criteria:

  • Part 1: History or presence of psychiatric disease/condition, GI, renal, hepatic, cardiovascular, psychiatric, or retinal diseases or disorders.
  • Part 2: Significant disease affecting the CNS other than Alzheimer's disease, including but not limited to other dementias, other significant neurological or major psychiatric disease.
  • 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.
  • History of neurological disease, including seizures, recent memory impairment, or clinically significant head injury.
  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: NCT01795339

Locations
United States, California
Research Site
Glendale, California, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Robert C Alexander, MD AstraZeneca
Principal Investigator: David Han, MD PAREXEL/CCT Early Phase Clinical Unit
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01795339     History of Changes
Other Study ID Numbers: D5010C00002
Study First Received: February 18, 2013
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by AstraZeneca:
AZD3293
Healthy volunteers
Elderly volunteers
Alzheimer's Disease patients
AD patients
Phase 1
Multiple Ascending Dose Study

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 21, 2014