Healthy Elderly Volunteers, Mild-to-moderate Alzheimer's Disease Patients
Conditions
Keywords
AZD3293, Healthy volunteers, Elderly volunteers, Alzheimer's Disease patients, AD patients, Phase 1, Multiple Ascending Dose Study
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
Interventions
DRUGAZD3293
Oral solution
DRUGPlacebo
Oral solution
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of telemetry, as reported by Investigator Columbia-Suicide Severity Rating Scale (C-SSRS) | From Baseline up to 20 days | 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. |
| Adverse event monitoring | From Baseline up to 20 days | — |
| Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams | From Baseline up to 20 days | — |
| Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety) | From Baseline up to 20 days | — |
| Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval | Fron Baseline up to 20 days | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | Up to 17 days |
| Investigation of the multiple dose Pharmacokinetics for AZD3293 and its metabolite AZ13569724, including dose proportionality for AZD3293 following oral administration | Up 17 days |
| Investigation of the Pharmacokinetics/Pharmacodynamics relationship of the effect of AZD3293 on biomarkers relevant for Alzheimer Disease (AD) in plasma | Up to 17 days |
| Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD) | Up to 17 days |
Countries
United States
Outcome results
None listed