Mild Dementia due to Alzheimer’s Disease MedDRA version: 20.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Xanamem™ 10 mg capsules
Product Code: UE2343
Pharmaceutical Form: Capsule
INN or Proposed INN: Not available
CAS Number: 1346013-80-6
Other descriptive name: UE2343
Concentration unit:
Sponsors
Actinogen Medical
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 50 years or older at the time of informed consent. 2. Female subjects: a) Post menopausal women, defined as no menses for 12 months without an alternative medical cause. If there is any concern about the menopausal status of a prospective female subject, a follicle stimulating hormone (FSH) test should be requested to confirm post menopausal status. Post-menopausal women confirmed by FSH level > 40 mIU/mL, will be confirmed by central laboratory. b) WOCBP must have a negative pregnancy test at Screening and Baseline and be willing to use highly effective methods of contraception from the Screening visit until 3 months after last dose of study drug. The central laboratory will flag positive serum human chorionic gonadotropin as exclusionary at Screening (re-test of Screening if required). In such cases, the site will perform a local urine pregnancy test at Baseline to determine if the subject can continue to randomisation (see Appendix IV for more information) c) Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy. d) Women must not be breastfeeding 3. Male subjects: a) Who are sexually active, fertile men must use highly effective methods of contraception from Day 1 until 3 months after last dose of study drug if their partners are WOCBP (see Appendix IV for more information). b) Who are permanently sterile or have had bilateral orchiectomy. 4. Diagnosis of mild dementia due to probable AD with increased level of certainty (provided by evidence of clinical deterioration within the 6 months preceding Screening, as assessed by the investigator) as determined by the National Institute of Ageing (NIA) and the Alzheimer’s Association (AA) workgroup. 5. Mild dementia due to probable AD with MMSE of 20 to 26 (inclusive). 6. CDR Global Score of 0.5 to 1.0. 7. A brain magnetic resonance imaging (MRI) or computed tomography (CT) scan in the 12 months preceding Screening (a wider window may be accepted but requires written approval by the ICON Medical Monitor (MM)) that, in the investigator’s opinion, is consistent with AD as the principal aetiology of the dementia with no other clinically significant abnormality, e.g. another principal underlying aetiology of the subject’s dementia, or a lesion which could affect cognition e.g. a brain tumour or large stroke. 8. On stable dose of acetylcholinesterase inhibitor (AChEI) and/or memantine (at least 3 months prior to Screening) OR treatment-naïve. Initiating AChEIs or memantine during the study will not be permitted. 9. Apart from a clinical diagnosis of mild dementia due to probable AD, the subject must be in good health as determined by the investigator, based on medical history and screening assessments. 10. Has a consenting study partner who, in the investigators judgement, has frequent and sufficient contact with the subject to be able to provide accurate information as to the subject’s cognitive and functional abilities. The study partner must be available to provide information to the investigator and study site staff about the subject and agrees to attend all study site visits in person for scale completion. A study partner should be available for the duration of the study. The measure of adequate availability will be at the investigators discretion. 11. Must be willing and able to comply with the requirements of the protocol and must be available to complete the study. 12. Must satisfy a medical
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator. 2. Clinically significant abnormal haematology, biochemistry and urine examination values, as determined by the investigator. Additionally, abnormal liver and renal function and Vitamin B12 levels below lower threshold may impact cognitive function. The following values will have an alert flag on the laboratory report and are specifically excluded: a) Vitamin B12 3 x upper limit of normal (ULN) d) Alanine aminotransferase > 3 x ULN e) Serum creatinine > 2 x ULN f) Urine benzodiazepines when positive: One re-test will be allowed in cases where the subject’s intake of benzodiazepines is within the allowed dose. Re-tests must be performed within 7 days of the last benzodiazepine dose prior to the Baseline visit. A positive re-test for urine benzodiazepines is exclusionary. 3. Has had a significant systemic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator. 4. Clinically significant neurological disease other than AD, such as (but not limited to) Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder, subdural haematoma, multiple sclerosis or a history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. 5. Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities. Clinical evidence of neuropathy is defined as: a) Inability to sense a stimulus even at the secondary (more proximal) skin area for pinprick, light touch, and vibration or temperature at the foot, in at least one extremity (in case of neurography measures are normal, the case will be discussed with the ICON MM to assess subject eligibility. b) Nerve conduction abnormalities beyond local normal values or inability to measure SNAP or CMAP in the primary or a secondary (back-up) nerve c) NTSS-6 score > 6, but note that subjects are eligible even if they show: • Missing reflexes of the Achilles tendon (ankle), but a positive patellar (knee) tendon reflex • Missing ability to name toe or thumb position 6. Has had a stroke within the year prior to randomisation, as determined by the investigator. 7. Has a lifetime diagnosis of a major psychiatric disorder (other than dementia), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. This includes but is not limited to schizophrenia, schizoaffective disorder, bipolar affective disorder, alcohol dependence syndrome or major depressive disorder. 8. Has a history of disease directly related to the hypothalamus, the pituitary and/or the adrenal glands which affect the hypothalamic-pituitary-adrenal axis function. 9. Has uncontrolled clinical conditions relating to glucose and lipid metabolism. 10. Clinically significant ECG abnormalities, including QTc interval > 450 msec, following ECG tracings at Screening. A single repeat evaluation will be allowed if the investigator or designee has reason to believe the reading is faulty or to help assess the clinical significance of an abnormality. Any other ECG abnormality that is seen as exclusio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the extent to which Xanamem™ improves performance from Baseline to end of treatment (EOT) compared to placebo, as measured by changes in AD COMposite Scores (ADCOMs, composite data derived from Alzheimer's Disease Assessment Scales - Cognitive subscale version 14 [ADAS-Cog v14], Clinical Dementia Rating Scale - Sum of Boxes [CDR-SOB], and Mini-Mental Status Examination [MMSE]) and ADAS-Cog v14 as primary endpoints in subjects with mild dementia due to probable AD.;Secondary Objective: To assess the extent to which Xanamem™ will improve performance from Baseline to EOT compared to placebo, as measured by changes to: • Rey Auditory Verbal Learning Test (RAVLT) • CDR-SOB • MMSE • Neuropsychiatric Inventory (NPI) • Neuropsychological Test Batteries (NTB) – Executive Domain ;Primary end point(s): Efficacy: The two primary efficacy variables are: 1) The change from Baseline (Week 0) to Week 12 /(end of treatment, EOT) in the Alzheimers Disease COMposite Score (ADCOMs), a composite score based on Alzheimer's Disease Assessment Scale - Cognitive subscale, version 14 (ADAS-Cog v14), Clinical Dementia Rating scale - Sum of Boxes (CDR-SOB) and Mini-Mental Status Examination (MMSE). 2) The change from Baseline (Week 0) to Week 12/EOT in the ADAS-Cog v14. Multiplicity between both primary endpoints will be handled using an a priori hierarchical approach, such that the results for the ADAS-Cog v14 will only be interpreted in a confirmatory fashion if results for the ADCOMs allowed a rejection of the null hypothesis. Safety Variables: •Clinical safety laboratory values • Adverse Events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs) • Electrocardiogram (ECG) • Nerve Function Monitoring (NFM) o Neuropathy Total Symptom Score (NTSS-6) o Toronto Clinical Neuropathy Score (TCNS) o NCV and amplitude of peripheral motor and sensory nerves o Vibration and Thermal Percepti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy The following secondary efficacy variables will be evaluated: • Rey Auditory Verbal Learning Test (RAVLT) • Clinical Dementia Rating scale - Sum of Boxes (CDR -SOB) • Mini-Mental Status Examination (MMSE) • Neuropsychiatric Inventory (NPI) • Neuropsychological Test Batteries (NTB) – Executive Domain (COWAT and CFT) ;Timepoint(s) of evaluation of this end point: • RAVLT: Baseline and Week 12/End of Treatment • CDR –SOB: Screening, Baseline, Week 12/End of Treatment • MMSE: Screening, Baseline, Week 12/End of Treatment • NPI (care-giver only): Baseline and Week 12/End of Treatment • NTB – Executive Domain: Baseline and Week 12/End of Treatment | — |
Countries
Australia, United Kingdom, United States
Contacts
Public ContactProject Management
ICON Clinical Research Pty Ltd
Outcome results
None listed