Clinical trial NCT01795339: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-02-20
Enrollment: 47
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Primary outcomes:
measure: Adverse event monitoring
timeFrame: From Baseline up to 20 days
measure: Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams
timeFrame: From Baseline up to 20 days
measure: Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety)
timeFrame: From Baseline up to 20 days
measure: Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval
timeFrame: Fron Baseline up to 20 days
measure: Assessment of telemetry, as reported by Investigator Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From Baseline up to 20 days
Secondary outcomes:
measure: Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD)
timeFrame: Up to 17 days
measure: 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
timeFrame: Up to 17 days
measure: Investigation of the multiple dose Pharmacokinetics for AZD3293 and its metabolite AZ13569724, including dose proportionality for AZD3293 following oral administration
timeFrame: Up 17 days
measure: Investigation of the Pharmacokinetics/Pharmacodynamics relationship of the effect of AZD3293 on biomarkers relevant for Alzheimer Disease (AD) in plasma
timeFrame: Up to 17 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
affiliation: AstraZeneca
name: Robert C Alexander, MD
role: STUDY_DIRECTOR
affiliation: PAREXEL/CCT Early Phase Clinical Unit
name: David Han, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.