Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, TRx0237, Safety Study, AD
Brief 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.
Interventions
DRUGTRx0237
TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks
DRUGPlacebo
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.
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 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine | 8 weeks | This was assessed by the number of participants who experienced adverse events within each treatment group (TRx0237 versus placebo) during 8 weeks of treatment. |
Countries
Germany, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TRx0237 One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237) | 5 |
| Placebo One placebo tablet containing 4-mg TRx0237 administered twice daily (8 mg/day TRx0237) | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | TRx0237 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 74.2 years STANDARD_DEVIATION 8.7 | 74.3 years STANDARD_DEVIATION 3.3 | 74.2 years STANDARD_DEVIATION 6.5 |
| Anti-dementia Therapy AChEI | 5 participants | 4 participants | 9 participants |
| Anti-dementia Therapy Both | 0 participants | 0 participants | 0 participants |
| Anti-dementia Therapy Memantine | 0 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United Kingdom | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 4 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
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.
Time frame: 8 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRx0237 | Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine | 4 participants |
| Placebo | Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine | 4 participants |