Intervention: Leucomethylene Blue dimesylate
Trial phase: Phase 2
SMILES: CN(C)c1ccc2c(c1)Sc1cc(N(C)C)ccc1N2.CS(=O)(=O)O.CS(=O)(=O)O
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237)
Eligibility criteria:
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