Safety Study of TRx0237 in Patients Already Taking Medications for Mild and Moderate Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: TRx0237; Placebo
Intervention description: TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 9.0
Sex: All
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Alzheimer's Disease; TRx0237; Safety Study; AD

Summary:

      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.
    

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