Phase 2a Dose Finding, PK/PD and 12 Month Exploratory Efficacy Study of ANAVEX2-73 in Patients With Alzheimer's Disease

NCT02244541 | Completed Phase 2 DMC

• 1 other identifier: ANAVEX2-73-002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of this Phase 2a study is to evaluate the maximal tolerated dose of ANAVEX2-73 in patients with AD in a repeated-dose administration scheme, with the secondary objectives being to explore the relationship between dosing regimen and pharmacodynamics efficacy outcomes and to evaluate the bioavailability of the oral form used and to explore the relationship of ANAVEX2-73 as add-on therapy to AD standard of care.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• To determine maximum tolerated dose of Anavex2-73.

  36 Days

Secondary Outcomes (7)

• PK sampling- blood test results

  First part (PART A), first period (hours): 1, 48, 264; second period (hours): 1, 72, 264; extension period (PART B): Week 1, 12 and 26.

• Mini-mental state examination score (MMSE)

  Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52

• Score from ADCS-ADL (Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory)

  Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52

• Cogstate Brief Battery (CBB) Score and International Shopping List Task (ISLT) Score

  At baseline, Day 1, 2, 6, 9, 12 of Period 1 and Day 1, 2, 6, 9, 12 of Period 2 and during the extension period at Week 12, 36, 48, and 52.

• Electroencephalographic activity, including event-related potentials (EEG/ERP)

  baseline, Day 1, 5, 11 of Period 1 and Day 1, 5, 11 of Period 2 and, Week 12, 36, 48, and 52 of the extension period

Study Arms (4)

Anavex2-73 oral then the Anavex2-73 intravenous formulation

EXPERIMENTAL

Participants first receive Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days. After a washout period of 11 days they then receive the Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days.

Drug: ANAVEX2-73 Oral; Drug: ANAVEX2-73 Intravenous

Anavex2-73 intravenous then the Anavex2-73 oral formulation

EXPERIMENTAL

Participants first receive Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days. After a washout period of 11 days then they receive the Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days.

Drug: ANAVEX2-73 Oral; Drug: ANAVEX2-73 Intravenous

Anavex2-73 30 mg oral formulation

EXPERIMENTAL

Participants will receive the 30 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks.

Drug: ANAVEX2-73 Oral

Anavex2-73 50 mg oral formulation

EXPERIMENTAL

Participants will receive the 50 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks.

Drug: ANAVEX2-73 Oral

Interventions

ANAVEX2-73 Oral DRUG

Anavex2-73 intravenous then the Anavex2-73 oral formulation; Anavex2-73 oral then the Anavex2-73 intravenous formulation

ANAVEX2-73 Intravenous DRUG

Anavex2-73 intravenous then the Anavex2-73 oral formulation; Anavex2-73 oral then the Anavex2-73 intravenous formulation

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Probable AD in accordance with NINCDS-ADRDA criteria.
• A brain CT or MRI scan performed within last 12 months from day of screening consistent with the clinical diagnosis of probable AD.
• Age from 55 to 85 years inclusive.
• MMSE score of 16-28 inclusive.
• Rosen Modified Hachinski Ischemic score \<=4.
• Community dwelling with caregiver who has regular contact with the subject for at least 10 hours per week and is able to oversee the patient's compliance with study medication and participate in the patient's clinical assessment and is capable of accompanying the participant on all clinic visits.
• Fluency in English.
• Be able to read, write, speak clearly for the cognitive tests, with eyesight and hearing sufficient to enable completion of the cognitive tests.
• Receiving stable doses of medications for the treatment of non-excluded medical conditions for at least 30 days prior to screening.

You may not qualify if:

• Dementia other than AD such as AIDS, CJD, LBD, CVD, Progressive Supranuclear Palsy, Multiple cerebral infarcts, or normal pressure hydrocephalus.
• Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumour.
• Current presence of a clinically significant major psychiatric disorder according to the criteria of the DSM-IV, or symptom that could affect the participant's ability to complete the study). HAM-D score \>12.
• Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
• Any other criteria which in the opinion of the Investigator causes the participant not to qualify for the study.

Sponsors & Collaborators

• Anavex Life Sciences Corp.: lead

Study Sites (5)

Melbourne Health - The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Austin Health - Heidelberg Repatriation Hospital

Melbourne, Victoria, 3084, Australia

Location

Caulfield Hospital

Melbourne, Victoria, 3162, Australia

Location

Nucleus Network- Centre for Clinical Studies

Melbourne, Victoria, Australia

Location

St. Vincent's Hospital

Melbourne, Victoria, Australia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

tetrahydro-N, N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Stephen Macfarlane

  Caulfield Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2014
• First Posted: September 19, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: November 28, 2018

Record last verified: 2018-11

Locations

AU (5)