Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, Alzheimer Disease, TRx0237, AD, Neurodegenerative Diseases, Dementia, Brain Diseases
Brief summary
The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild Alzheimer's Disease.
Interventions
DRUGTRx0237 200 mg/day
TRx0237 100 mg tablets will be administered twice daily.
DRUGPlacebo
Placebo tablets will be administered twice daily. The active placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence the placebo group will receive a total of 8 mg/day of TRx0237.
Sponsors
TauRx Therapeutics Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 89 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of all cause dementia and probable Alzheimer's disease * Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) and MMSE score of 20-26 (inclusive) * Age \<90 years * Modified Hachinski ischemic score of ≤4 * Females, if of child-bearing potential, must practice true abstinence or be competent to use adequate contraception and agree to maintain this throughout the study * Subject, and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law is/are able to read, understand, and provide written informed consent * Has one (or more) identified adult caregiver who is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug * If currently taking an acetylcholinesterase inhibitor and/or memantine at the time of Screening, the subject must have been taking such medication(s) for ≥3 months. The dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain stable throughout participation in the study. * Able to comply with the study procedures
Exclusion criteria
* Significant central nervous system (CNS) disorder other than Alzheimer's disease * Significant focal or vascular intracranial pathology seen on brain MRI scan * Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes * Epilepsy * Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders * Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI * Resides in hospital or moderate to high dependency continuous care facility * History of swallowing difficulties * Pregnant or breastfeeding * Glucose-6-phosphate dehydrogenase deficiency * History of significant hematological abnormality or current acute or chronic clinically significant abnormality * Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator * Clinically significant cardiovascular disease or abnormal assessments * Preexisting or current signs or symptoms of respiratory failure * Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease * Diagnosis of cancer within the past 2 years prior to Baseline (other than basal cell or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted in complete freedom from disease for at least 2 years * Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar organic dyes, or any of the excipients * Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted): * Tacrine * Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study) * Carbamazepine, primidone * Drugs with a warning or precaution in the labeling of methemoglobinemia at approved doses * Current or prior participation in a clinical trial as follows: * Clinical trial of a product for cognition in which the last dose was received within 90 days prior to Screening (unless confirmed to have been randomized to placebo) * A clinical trial of a drug, biologic, device, or medical food in which the last dose/administration was received within 28 days prior to Baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes | 78 weeks | Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for serotonin toxicity, brain magnetic resonance imaging (MRI), and potential for suicide or self-harm. |
| Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) | 78 weeks | — |
| Change from Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) | 78 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | 78 weeks |
| Change in expected decline of whole brain volume as measured by brain MRI | 78 weeks |
| Change from Baseline in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | 78 weeks |
| Change from Baseline in Mini-Mental Status Examination (MMSE) | 78 weeks |
| Change from Baseline in Neuropsychiatric Inventory (NPI) | 78 weeks |
Other
| Measure | Time frame |
|---|---|
| Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging | 78 weeks |
| Change in expected increase in ventricular volume as measured by brain MRI | 78 weeks |
| Change in expected decline in hippocampal volume as measured by brain MRI | 78 weeks |
| Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided | 78 weeks |
| Change in cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture | 78 weeks |
| Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite | 78 weeks |
Countries
Australia, Belgium, Canada, Croatia, Finland, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Outcome results
None listed