Safety Study of TRx0237 in Patients Already Taking Medications for Mild and Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety and tolerability of TRx0237 when taken at the same time as acetylcholinesterase inhibitors (i.e., donepezil, galantamine, or rivastigmine) and / or memantine to treat patients with mild to moderate Alzheimer's Disease.

Official Title
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A Double-Blind, Placebo-Controlled, Randomised, 4-Week Safety and Tolerability Study of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease on Pre-Existing Stable Acetylcholinesterase Inhibitor and/or Memantine Therapy

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: TRx0237
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Clinical diagnosis of all cause dementia and probable Alzheimer's disease (AD) Mini-Mental State Examination (MMSE) score of 14-26 (inclusive) Cognitive impairment present for at least 6 months Age ≤90 years Modified Hachinski ischaemic score of ≤4 Females, if of childbearing potential, must use adequate contraception and maintain this use throughout participation in the study Patient is able to read, understand, and provide written informed consent Has one or more identified caregivers who are able to verify daily compliance with study drug and provide information on safety and tolerability; the caregiver(s) must also give consent to participate Currently taking an taking an acetylcholinesterase inhibitor and/or memantine; 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 disorder other than Alzheimer's disease Patients in whom baseline MRI is contraindicated such as metal implants in head (except dental), pacemaker, and cochlear implant Significant focal or intracranial pathology that would lead to a diagnosis other than probable Alzheimer's disease Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness Epilepsy Major depressive disorder, schizophrenia or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders Resides in a hospital or continuous care facility History of swallowing difficulties Pregnant or breastfeeding 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 Pre-existing or current signs or symptoms of respiratory failure Concurrent acute or chronic clinically significant immunologic, renal, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease Prior intolerance to methylthioninium-containing drug or any of the excipients Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted): Tacrine Anxiolytics and/or sedatives/hypnotics (exceptions: sedation for MRI or occasional short-acting benzodiazepines, chloral hydrate, or zolpidem as needed at bedtime) Antipsychotics (clozapine, chlorpromazine, thioridazine, or ziprasidone) Carbamazepine Drugs associated with methaemoglobinaemia (e.g., dapsone, local anesthetics such as benzocaine used chronically, primaquine and related antimalarials, sulfonamides) Warfarin (and other Coumadin derivates such as phenprocoumon) Current or prior participation in a clinical trial of a drug, biologic, or device in which the last dose was received within 28 days prior to Baseline

Ages Eligible for Study
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Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRx0237<br> | Drug: TRx0237<br>* TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablets will be administered twice daily (b.i.d.) for 4 weeks. The placebo tablets include 4 mg of TRx0237 as a urinary and faecal colourant to maintain blinding; hence, the placebo group will receive a total of 8 mg/day of TRx0237.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine | This was assessed by the number of participants who experienced adverse events within each treatment group (TRx0237 versus placebo) during 8 weeks of treatment. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AD, Alzheimer's Disease, TRx0237, Safety Study