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

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

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.

Study Overview

• Status: Completed
• Conditions: Maximum Diagnostic Mass of [18Fluor]AZD4694
• Intervention / Treatment: Other: [18Fluor]AZD4694; Other: [18Fluor]AZD4694; Other: [18Fluor]AZD4694

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Research Site
  • Uppsala, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Cohort 1; Patients with mild to moderate Alzheimer's Disease	Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 40 and 50 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 20 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose will be the Maximum Detective Mass established in the previous panels.
Experimental: Part 1 Cohort 2; Patients with mild to moderate Alzheimer's Disease. To run if Maximum Detective Mass is detected in cohort 1.	Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 40 and 50 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 20 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose will be the Maximum Detective Mass established in the previous panels.
Experimental: Part 2; Healthy Volunteers	Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 40 and 50 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose around 20 ug.; Other: [18Fluor]AZD4694; Low mass dose below 5ug. High mass dose will be the Maximum Detective Mass established in the previous panels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Visit 3
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)	Visit 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events as a measure of Safety and tolerability of [18F]AZD4694	Range of Visits 3-5
Correlation between early uptake of [18F]AZD4694 images and cerebral blood flow images as measured by Arterial Spin Labeling Magnetic resonance imaging	Range of Screening Visit to Visit 4
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	Range of Screening Visit to Visit 4

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Bjorn Paulsson, AstraZeneca; Principal Investigator: Niels Andreasen, MD, Geriatric clinic Karolinska University Hospital Huddinge; Principal Investigator: Elisabeth Eden, MD, Quintiles Aktiebolag

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: March 21, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 7, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Radioligand; Alzheimers disease; Maximum Diagnostic Mass; Beta amyloid
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: D2750C00002; EudraCT # 2011-000095-34