An Open Positron Emission Tomography Study to Assess the Effects of Varying Mass of AZD4694 on Radioligand Binding Parameters in Healthy Volunteers and Patients With Alzheimer's Disease
Primary Purpose
Maximum Diagnostic Mass of [18Fluor]AZD4694
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
[18Fluor]AZD4694
[18Fluor]AZD4694
[18Fluor]AZD4694
Sponsored by
About this trial
This is an interventional basic science trial for Maximum Diagnostic Mass of [18Fluor]AZD4694 focused on measuring Radioligand, Alzheimers disease, Maximum Diagnostic Mass, Beta amyloid
Eligibility Criteria
Inclusion Criteria:
- Body Mass Index between 18 and 30 kg/m2 and weigh at least 50kg and no more than 100 kg.
- Mini Mental State Examination score >28 (healthy volunteers only)
- Mini Mental State Examination score 16-28 (Alzheimer's Disease patients only)
- Hachinski Ischemic Score =4 (Alzheimer's Disease patients only)
- Clinical diagnosis of probable Alzheimer's Disease according to National Institute of Neurology and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (Alzheimer's Disease patients only)
Exclusion Criteria:
- Significant Neurological disease or dementia, as defined clinically or by imaging, other than Alzheimer's Disease that may affect cognition or ability to complete the study (Alzheimer's Disease patients only).
- Possible, probable or definite vascular dementia in accordance with the National Institute of neurology and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders association criteria (Alzheimer's Disease patients only).
- Current major depressive disorder or other major psychiatric disorders according to Diagnostic and Statistical Manual of Mental Disorders, edition 4, American Psychiatric Association 1994 criteria (Alzheimer's disease patients only).
- Depression: Cornell Depression Rating >9 (Alzheimer's disease patients only).
- Abnormal vital signs defined as any of the following: Systolic blood pressure >180 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or>85 beats per minute (Alzheimer's disease patients only).
- Myocardial infarction or acute coronary syndrome within the last year (Alzheimer's disease patients only).
- Had Positron Emission Tomography measurements for scientific purposes within the last 12 months.
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study (healthy volunteers only).
- History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs (healthy volunteers only).
- History of previous (within the last 5 years) or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder according to the criteria in to Diagnostic and Statistical Manual of Mental Disorders, edition 4, American Psychiatric Association 1994, as assessed by the Mini international neuropsychiatric interview (healthy volunteers only).
- Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of Investigational Product (healthy volunteers only).
- Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator (healthy volunteers only).
- Healthy volunteers<65 years: abnormal vital signs defined as any of the following: Systolic blood pressure >140 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or>85 beats per minute.
- Healthy volunteers≥65 years: abnormal vital signs defined as any of the following: Systolic blood pressure >160 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or >85 beats per minute.
- Central Nervous system infarct, infection of focal lesions of clinical significance on MRI scans as judged by the investigator.
Sites / Locations
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1 Cohort 1
Part 1 Cohort 2
Part 2
Arm Description
Patients with mild to moderate Alzheimer's Disease
Patients with mild to moderate Alzheimer's Disease. To run if Maximum Detective Mass is detected in cohort 1.
Healthy Volunteers
Outcomes
Primary Outcome Measures
The Maximum Diagnostic Mass by assessing the visual read out of amyloid status according to and quantification of an [18F]AZD4694 PET image in a high mass experiment compared to the image in a low mass experiment in the same subject.
Measuring the maximum chemical mass not causing any significant alteration of the amyloid status (unit = micrograms)
The Maximum Diagnostic Mass by assessing the visual read out of amyloid status according to and quantification of an [18F]AZD4694 PET image in a high mass experiment compared to the image in a low mass experiment in the same subject.
Measuring the maximum chemical mass not causing any significant alteration of the amyloid status (unit = micrograms)
Secondary Outcome Measures
Number of Adverse Events as a measure of Safety and tolerability of [18F]AZD4694
Correlation between early uptake of [18F]AZD4694 images and cerebral blood flow images as measured by Arterial Spin Labeling Magnetic resonance imaging
Correlation between estimates of β-amyloid load in brain obtained using [18F]AZD4694 Position Emission Tomography imaging and concentrations of β-amyloid in Cerebrospinal fluid
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01325402
Brief Title
An Open Positron Emission Tomography Study to Assess the Effects of Varying Mass of AZD4694 on Radioligand Binding Parameters in Healthy Volunteers and Patients With Alzheimer's Disease
Official Title
Open-Label Positron Emission Tomography Study With Selective Beta Amyloid Radioligand (18Fluor)AZD4694 to Assess the Effects of Varying Mass of AZD4694 on Radioligand Binding Parameters in Healthy Volunteers and Patients With Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this study different mass of the radioligand AZD4694 will be given to patients with Alzheimer's Disease and healthy volunteers to evaluate wich Mass of AZD4694 that gives the best opportunities for following disease progress and treatment effects.
Detailed Description
Open-Label Positron Emission Tomography Study with Selective Beta Amyloid Radioligand (18Fluor)AZD4694 to Assess the Effects of Varying Mass of AZD4694 on Radioligand Binding Parameters in Healthy Volunteers and Patients with Alzheimer's Disease
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Maximum Diagnostic Mass of [18Fluor]AZD4694
Keywords
Radioligand, Alzheimers disease, Maximum Diagnostic Mass, Beta amyloid
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 Cohort 1
Arm Type
Experimental
Arm Description
Patients with mild to moderate Alzheimer's Disease
Arm Title
Part 1 Cohort 2
Arm Type
Experimental
Arm Description
Patients with mild to moderate Alzheimer's Disease. To run if Maximum Detective Mass is detected in cohort 1.
Arm Title
Part 2
Arm Type
Experimental
Arm Description
Healthy Volunteers
Intervention Type
Other
Intervention Name(s)
[18Fluor]AZD4694
Intervention Description
Low mass dose below 5ug. High mass dose around 40 and 50 ug.
Intervention Type
Other
Intervention Name(s)
[18Fluor]AZD4694
Intervention Description
Low mass dose below 5ug. High mass dose around 20 ug.
Intervention Type
Other
Intervention Name(s)
[18Fluor]AZD4694
Intervention Description
Low mass dose below 5ug. High mass dose will be the Maximum Detective Mass established in the previous panels.
Primary Outcome Measure Information:
Title
The Maximum Diagnostic Mass by assessing the visual read out of amyloid status according to and quantification of an [18F]AZD4694 PET image in a high mass experiment compared to the image in a low mass experiment in the same subject.
Description
Measuring the maximum chemical mass not causing any significant alteration of the amyloid status (unit = micrograms)
Time Frame
Visit 3
Title
The Maximum Diagnostic Mass by assessing the visual read out of amyloid status according to and quantification of an [18F]AZD4694 PET image in a high mass experiment compared to the image in a low mass experiment in the same subject.
Description
Measuring the maximum chemical mass not causing any significant alteration of the amyloid status (unit = micrograms)
Time Frame
Visit 4
Secondary Outcome Measure Information:
Title
Number of Adverse Events as a measure of Safety and tolerability of [18F]AZD4694
Time Frame
Range of Visits 3-5
Title
Correlation between early uptake of [18F]AZD4694 images and cerebral blood flow images as measured by Arterial Spin Labeling Magnetic resonance imaging
Time Frame
Range of Screening Visit to Visit 4
Title
Correlation between estimates of β-amyloid load in brain obtained using [18F]AZD4694 Position Emission Tomography imaging and concentrations of β-amyloid in Cerebrospinal fluid
Time Frame
Range of Screening Visit to Visit 4
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body Mass Index between 18 and 30 kg/m2 and weigh at least 50kg and no more than 100 kg.
Mini Mental State Examination score >28 (healthy volunteers only)
Mini Mental State Examination score 16-28 (Alzheimer's Disease patients only)
Hachinski Ischemic Score =4 (Alzheimer's Disease patients only)
Clinical diagnosis of probable Alzheimer's Disease according to National Institute of Neurology and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (Alzheimer's Disease patients only)
Exclusion Criteria:
Significant Neurological disease or dementia, as defined clinically or by imaging, other than Alzheimer's Disease that may affect cognition or ability to complete the study (Alzheimer's Disease patients only).
Possible, probable or definite vascular dementia in accordance with the National Institute of neurology and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders association criteria (Alzheimer's Disease patients only).
Current major depressive disorder or other major psychiatric disorders according to Diagnostic and Statistical Manual of Mental Disorders, edition 4, American Psychiatric Association 1994 criteria (Alzheimer's disease patients only).
Depression: Cornell Depression Rating >9 (Alzheimer's disease patients only).
Abnormal vital signs defined as any of the following: Systolic blood pressure >180 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or>85 beats per minute (Alzheimer's disease patients only).
Myocardial infarction or acute coronary syndrome within the last year (Alzheimer's disease patients only).
Had Positron Emission Tomography measurements for scientific purposes within the last 12 months.
History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study (healthy volunteers only).
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs (healthy volunteers only).
History of previous (within the last 5 years) or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder according to the criteria in to Diagnostic and Statistical Manual of Mental Disorders, edition 4, American Psychiatric Association 1994, as assessed by the Mini international neuropsychiatric interview (healthy volunteers only).
Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of Investigational Product (healthy volunteers only).
Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator (healthy volunteers only).
Healthy volunteers<65 years: abnormal vital signs defined as any of the following: Systolic blood pressure >140 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or>85 beats per minute.
Healthy volunteers≥65 years: abnormal vital signs defined as any of the following: Systolic blood pressure >160 mmHg, Diastolic blood pressure >90 mmHg, heart rate <40 or >85 beats per minute.
Central Nervous system infarct, infection of focal lesions of clinical significance on MRI scans as judged by the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bjorn Paulsson
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Niels Andreasen, MD
Organizational Affiliation
Geriatric clinic Karolinska University Hospital Huddinge
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elisabeth Eden, MD
Organizational Affiliation
Quintiles Aktiebolag
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Stockholm
Country
Sweden
Facility Name
Research Site
City
Uppsala
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
An Open Positron Emission Tomography Study to Assess the Effects of Varying Mass of AZD4694 on Radioligand Binding Parameters in Healthy Volunteers and Patients With Alzheimer's Disease
We'll reach out to this number within 24 hrs