A Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer's Patients

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Elderly Volunteers; Mild-to-moderate Alzheimer's Disease Patients
• Intervention / Treatment: Drug: AZD3293; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD3293; 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	Drug: AZD3293; Oral solution
Placebo Comparator: Placebo; Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)	Drug: Placebo; Oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.	From Baseline up to 20 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD)	Up to 17 days
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Robert C Alexander, MD, AstraZeneca; Principal Investigator: David Han, MD, PAREXEL/CCT Early Phase Clinical Unit

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: February 18, 2013
• First Submitted That Met QC Criteria: February 18, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers; Phase 1; AZD3293; Elderly volunteers; Alzheimer's Disease patients; AD patients; Multiple Ascending Dose Study
• 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: D5010C00002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No