Alzheimer's Disease MedDRA version: 20.0 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852 MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: ANAVEX2-73
Pharmaceutical Form: Capsule
INN or Proposed INN: Blarcamesine
CAS Number: 195615-84-0
Current Sponsor code: ANAVEX2-73
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
ANAVEX Life Sciences Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients aged 60 to 85 years, inclusive, with a NIA-AA diagnosis of mild cognitive impairment (MCI) due to AD or early stage mild dementia due to AD. AD diagnosis must be made by an appropriately qualified board-certified or equivalent medical specialist. 2. At least one of the following criterion must be utilized to support AD diagnosis: a. Historical records of amyloid CSF assessment or b. Historical records of PET scan (amyloid scan or FDG-PET) or c. Historical CT or MRI scan within 18 months of screening, which are consistent with a diagnosis of AD. CSF collection or PET scan would be required as part of the screening process unless historical records (CSF or PET) are available, except for participants in Australia and United Kingdom (UK). 3. Mini Mental State Examination (MMSE) score between 20-28, inclusive at both the Screening Visit and the Randomization Visit. 4. Free Recall score =17 or Total Recall score =65 years) yes F.1.3.1 Number of subjects for this age range 382
Exclusion criteria
Exclusion criteria: 1. Patients who have a progressive medical or neurological condition that in the opinion of the investigator would interfere with the conduct of the study. Exception: If diagnosed with seizures, must be on stable anti-seizure medication for at least 3 months prior to screening. 2. 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. 3. History or clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque. 4. History of neurologic (e.g., stroke, traumatic brain injury) or psychiatric condition that the investigator deems may interfere with interpretability of data. 5. History of untreated thyroid disorder, Type 1 diabetes, and insulin dependent or uncontrolled Type II diabetes, as determined by the investigator (e.g., non-insulin-controlled Type II diabetes, whose HbA1c value is higher than 8.0%). 6. If a participant has a Body Mass Index (BMI) > 35, no co-morbidities, related to weight that would preclude participation in the study in the opinion of the investigator. 7. History of clinical hepatic dysfunction. 8. Current symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hematological or hormonal disorders. 9. Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal (ULN) as determined during screening. 10. Significant history of drug addiction (with the exception of nicotine dependence) or abuse (including alcohol, as defined in DSM-5 or in the opinion of the investigator) within the last two years prior to informed consent, or a positive urine drug screen for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at screening. Prescription medication yielding a positive drug screen are acceptable except for tricyclic antidepressants (e.g., Amitriptyline, Amoxapine, Desipramine, (Norpramin) Doxepin, Imipramine (Tofranil), Nortriptyline (Pamelor), Protriptyline (Vivactil), Trimipramine (Surmontil)). 11. Clinically significant infection within the last 30 days prior screening (e.g., chronic persistent or acute infection, urinary tract infections (UTI)). 12. Treatment with tricyclic antidepressants 60 days prior to screening. 13. Treatment with immunosuppressive medications (e.g., systemic corticosteroids), within 90 days prior to screening (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted), or chemotherapeutic agents for malignancy within the last 3 years. 14. Myocardial infarction within the last year. 15. History of cancer within the last 3 years, with the exception of basal cell carcinoma and non-metastatic squamous cell carcinoma of the skin and prostate cancer with currently normal PSA. 16. Other clinically significant abnormality on physical, neurological, laboratory, or electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the participant. 17. Hemoglobin 1 pack of cigarettes per day (as assessed for the 30 days prior to screening). 19. Alcohol use of more than 2 drinks per day. 20. Current use of over-the-counter (OTC) supplements or nutraceuticals unless they are on stable dose for at least 3 months prior to screening and are documented in the eCRF. 21. Use of over the counter (OTC) or prescrip
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo. 2. Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo. ;Secondary Objective: 1. Change from baseline to week 48 on Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo. 2. To establish safety and tolerability of ANAVEX2-73 in patients with AD. 3. To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess retrospectively reported sleep continuity (RSCAQ) and the Insomnia Severity Index (ISI). ;Primary end point(s): Primary Efficacy Analysis The primary endpoints, ADAS-Cog and ADCS-ADL, and their corresponding change from baseline values will be summarized by visit and treatment group. Differences between each active treatment group and placebo at week 48 will be assessed based on the LSMeans from a mixed effects repeated measures ANCOVA model with fixed effects for treatment group, visit, treatment by visit interaction, absence/presence of the rs1800866 or rs113895332/rs61143203 variants, and baseline value, and a random effect for subject. ;Timepoint(s) of evaluation of this end point: Change from baseline to week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Analysis Similar statistical methods from the primary efficacy analysis (ADAS-Cog and ADCS-ADL) will be applied to CDR-SB. ;Timepoint(s) of evaluation of this end point: Change from baseline to week 48 | — |
Countries
Australia, Canada, Germany, Netherlands, United Kingdom
Contacts
Public ContactMoyra Coull
ORPHAN REACH Ltd.
Outcome results
None listed