Alzheimer’s Disease MedDRA version: 14.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Leuco-methylthioninium bis(hydromethanesulfonate)
Product Code: TRx0237
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: 1236208-20-0
Current Sponsor code: TRx0237
Concen
Sponsors
TauRx Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis according to NIA/AA criteria of • All cause dementia and • Probable Alzheimer’s disease 2. MMSE score of 14-26 (inclusive) at Screening 3. Cognitive impairment present for at least 6 months 4. Age = 90 years 5. Modified Hachinski ischemic score of = 4 at Screening 6. Females must meet one of the following: • Surgically sterile (hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 months minimum • Have undergone bilateral tubal /occlusion / ligation at least 6 months prior • Post-menopausal for at least 1 year (confirmed by follicle stimulating hormone [FSH] level at Screening = 30 mIU/mL; if a female patient is on hormone replacement therapy [HRT], a decision regarding FSH levels will be made by the investigator on a case by case basis) • Using adequate contraception (such as condoms, diaphragm or cervical/vault caps with spermicidal foam, gel, film, cream, suppository; intrauterine device or system, oral or long acting injected or implanted hormonal contraceptives for at least 3 months prior to Baseline; or vasectomised partner [with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate]); or true abstinence (when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception); patients must agree to continue to maintain adequate contraception throughout participation in the study (until the final off-treatment visit) 7. Patient is able to read, understand, and provide written informed consent in the designated language of the study site 8. 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. 9. Currently taking an AChEI (i.e., donepezil, galantamine, or rivastigmine) and/or memantine: • The patient must have been taking such medication(s) for = 3 months • The current dosage regimen and dosage form must be within the locally approved dose range and must have remained stable for = 6 weeks before Baseline (Visit 2) • It must be planned that the dosage regimen will remain stable throughout participation in the study 10. Able to comply with the study procedures in the view of the investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Significant CNS disorder other than Alzheimer’s disease (e.g., Parkinson’s disease, multiple sclerosis, progressive supranuclear palsy, hydrocephalus, Huntington’s disease) 2. Patients in whom baseline MRI is contraindicated such as metal implants in head (except dental), pacemaker, and cochlear implants. MRI obtained using 1.5 or 3 Tesla machines using T1, T2*-weighted gradient-recalled echo and FLAIR sequences of sufficient quality at screening or within a maximum of 28 days before Baseline demonstrating: oSignificant intracranial pathology that would lead to a diagnosis other than probable Alzheimer’s disease o>4 cerebral microhaemorrhages (regardless of their anatomical location or diagnostic characterisation as “possible” or “definite”), any single area of superficial siderosis, or evidence of a prior macrohaemorrhage 3. Clinical evidence or history of any of the following within specified period: •Cerebrovascular accident (2 years) •Transient ischemic attack (6 months) •Significant head injury with associated loss of consciousness, skull fracture or persisting cognitive impairment (2 years) •Other unexplained or recurrent loss of consciousness (2 years) 4. Epilepsy (a single prior seizure related to the patient’s Alzheimer’s disease or seizures limited to childhood febrile seizures is considered acceptable) 5. DSM-IV-TR criteria met for current major depressive disorder or schizophrenia or other psychotic disorders, bipolar disorder (within the past 5 years), or substance (including alcohol) related disorders (within the past 2 years) 6. Resides in a hospital or continuous care facility 7. History of swallowing difficulties 8. Pregnant or breastfeeding 9. History of significant haematological abnormality or current acute or chronic clinically significant abnormality, including: •History of hereditary or acquired methaemoglobinaemia or baseline measurement of MetHb >2.0% (confirmed on repeat) •History of haemoglobinopathy, myelodysplastic syndrome, haemolytic anaemia, or splenectomy •G6PD •Baseline value below age/sex appropriate lower limit of the central laboratory normal range for haemoglobin 10. Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator. In addition, patients with the following abnormalities must be excluded: •Creatinine clearance 450 msec in males or >470 msec in females, or low or flat T waves making measurement of QT interval unreliable •Recent history of poorly controlled hypertension, systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg •Systolic blood pressure 96 bpm •Significant orthostatic hypotension (decrease in systolic blood pressure of >20 mmHg after 2 minutes upon standing from seated position) 12. Pre-existing or current signs or symptoms of respiratory failure •Patients previously diagnosed with moderate to severe slee
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of leuco-methylthioninium bis(hydromethanesulfonate) (LMTM) 250 mg daily when co-administered with an acetylcholinesterase inhibitor (AChEI) and/or memantine to patients with mild to moderate Alzheimer’s disease. As exploratory objectives, markers of monoamine oxidase (MAO) inhibition will be assessed and blood samples collected for separate population pharmacokinetic analysis.;Secondary Objective: N/A;Primary end point(s): All adverse events (AEs), vital signs, 12-lead ECGs, clinical laboratory findings, physical and neurological examinations, and the potential for suicide or self-harm.;Timepoint(s) of evaluation of this end point: • Adverse events will be recorded at Visits 1 to 7 • Vital signs will be measured at Visits 1 to 7 for blood pressure and pulse and at Visits 2 to 7 for oral temperature and respiratory rate •12-lead ECG will be recorded at Visits 1 to 7 •Clinical laboratory tests will be performed at Visits 1, 2, 4, 5, 6, and 7 •Physical and neurological examinations will take place at Visits 1 to 7 •Serotonin toxicity assessments will be performed at Visits 2 to 7 •The potential for suicide or self-harm (Columbia Suicide Severity Rating Scale) will be assessed at Visits 2 to 7 •Methaemoglobin will be measured at Visits 1 to 7 •Blood samples will be taken at various timepoints during the study for measurement of troponin-I, AChEI and/or memantine plasma levels, MT plasma levels, and PD assessments | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Germany, United Kingdom
Contacts
Public ContactInformation Desk
TauRx Therapeutics Ltd
Outcome results
None listed