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

NCT01795339 | Completed Phase 1

• 1 other identifier: D5010C00002
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• 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

Study Arms (2)

AZD3293

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)

Drug: Placebo

Interventions

AZD3293 DRUG

Oral solution

AZD3293

Placebo DRUG

Oral solution

Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Glendale, California, United States

Location

Related Publications (1)

• 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.

  PMID: 29199322 DERIVED

MeSH Terms

Interventions

lanabecestat

Study Officials

• Robert C Alexander, MD

  AstraZeneca

  STUDY DIRECTOR

• David Han, MD

  PAREXEL/CCT Early Phase Clinical Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2013
• First Posted: February 20, 2013
• Study Start: March 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 3, 2014

Record last verified: 2014-04

Locations

US (1)