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

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