Back to resultsA Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer's Patients
Primary Purpose
Healthy Elderly Volunteers, Mild-to-moderate Alzheimer's Disease Patients
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD3293
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Healthy Elderly Volunteers focused on measuring AZD3293, Healthy volunteers, Elderly volunteers, Alzheimer's Disease patients, AD patients, Phase 1, Multiple Ascending Dose Study
Eligibility 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.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD3293
Placebo
Arm Description
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
Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)
Outcomes
Primary Outcome Measures
Adverse event monitoring
Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams
Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety)
Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval
Assessment of telemetry, as reported by Investigator 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.
Secondary Outcome Measures
Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD)
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
Investigation of the multiple dose Pharmacokinetics for AZD3293 and its metabolite AZ13569724, including dose proportionality for AZD3293 following oral administration
Investigation of the Pharmacokinetics/Pharmacodynamics relationship of the effect of AZD3293 on biomarkers relevant for Alzheimer Disease (AD) in plasma
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01795339
Brief Title
A Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer's Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Elderly Volunteers, Mild-to-moderate Alzheimer's Disease Patients
Keywords
AZD3293, Healthy volunteers, Elderly volunteers, Alzheimer's Disease patients, AD patients, Phase 1, Multiple Ascending Dose Study
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD3293
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)
Intervention Type
Drug
Intervention Name(s)
AZD3293
Intervention Description
Oral solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral solution
Primary Outcome Measure Information:
Title
Adverse event monitoring
Time Frame
From Baseline up to 20 days
Title
Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams
Time Frame
From Baseline up to 20 days
Title
Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety)
Time Frame
From Baseline up to 20 days
Title
Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval
Time Frame
Fron Baseline up to 20 days
Title
Assessment of telemetry, as reported by Investigator Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
From Baseline up to 20 days
Secondary Outcome Measure Information:
Title
Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD)
Time Frame
Up to 17 days
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert C Alexander, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
David Han, MD
Organizational Affiliation
PAREXEL/CCT Early Phase Clinical Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Glendale
State/Province
California
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29199322
Citation
Cebers G, Lejeune T, Attalla B, Soderberg M, Alexander RC, Budd Haeberlein S, Kugler AR, Ingersoll EW, Platz S, Scott CW. Reversible and Species-Specific Depigmentation Effects of AZD3293, a BACE Inhibitor for the Treatment of Alzheimer's Disease, Are Related to BACE2 Inhibition and Confined to Epidermis and Hair. J Prev Alzheimers Dis. 2016;3(4):202-218. doi: 10.14283/jpad.2016.119.
Results Reference
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A Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer's Patients
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