Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 12-Month Trial of Leuco methylthioninium bis (hydromethanesulfonate) in Subjects with Mild to Moderate Alzheimer's Disease
- Conditions
- Diseases of the nervous system
- Registration Number
- KCT0001134
- Lead Sponsor
- TauRx Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 88
Protocol V3_21Aug2013
1.Diagnosis according to the National Institute on Aging(NIA) and Alzheimer’s Association(AA)criteria of: All cause dementia and Probable Alzheimer’s disease
2.Clinical Dementia Rating(CDR) total score of 1(mild) to 2(moderate) and
Mini-Mental State Examination(MMSE) score of 14-19(moderate) to 20-26(mild) at Screening
3.Age <90years at Screening
4.Modified Hachinski ischemic score of =4 at Screening
5.Females must meet one of the following:
? Surgically sterile(hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 mons minimum
? Have undergone bilateral tubal occlusion / ligation at least 6 months prior
? Post-menopausal for at least 1 year
? 1) Using adequate contraception (a barrier method [such as condom, diaphragm or cervical/vault cap] with spermicidal foam, gel, film, cream, or suppository; intrauterine device [IUD] or system; or oral or long-acting injected or implanted hormonal contraceptives for at least 3 months prior to Baseline; or vasectomized partner [with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate]); or 2) true abstinence (when this is in line with the preferred and usual lifestyle of the subject);
3) subjects must be competent to use adequate contraception and to agree to maintain adequate contraception throughout participation in the study
6.Subject and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law, is/are able to read, understand, and provide written informed consent in the designated language of the study site.
7.Has one or more identified caregiver who meet the following criteria:
? Either (1) lives with the subject or (2) sees the subject on average for =2hrs/day =3days/ wk, or (3) in the investigator’s opinion, the extent of contact is sufficient to provide meaningful assessment of changes in subject behavior and function over time and provide information on safety and tolerability
? Is willing to provide written informed consent for his/her own participation
? Is able to read, understand, and speak the designated language at the study site
? Agrees to accompany the subject to each study visit
? Is able to verify daily compliance with study drug
8.If currently taking an acetylcholinesterase inhibitor(AChEI), i.e., donepezil, galantamine, or rivastigmine, and/or memantine at the time of screening:
? The subject 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
? It must be planned that the dosage regimen will remain stable throughout participation in the study
- Subjects not being treated with an AChEI or memantine(for =6 wks before Baseline Screening) may also be enrolled if initiation of an AChEI or memantine is not planned for the time period during which the subject will be participating in this study
9.Able to comply with the study procedures in the view of the investigator
Protocol V3_21Aug2013
1.Significant CNS disorder other than Alzheimer’s disease, e.g., Lewy body dementia,Parkinson’s disease, multiple sclerosis, progressive supra-nuclear palsy, hydrocephalus, Huntington’s disease,any condition directly or indirectly caused by Transmissible Spongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD)
2.Significant focal or vascular intracranial pathology seen on brain MRI scan within a maximum of 42days before Baseline(=Day1) that would, based on the independent reviewer imaging evaluation, lead to a diagnosis other than probable Alzheimer’s disease or that puts the subject at risk of Amyloid Related Imaging Abnormalities (ARIA), including:
? Large confluent white matter hyperintense lesions (i.e., Fazekas score of 3)
? Other focal brain lesions judged clinically relevant by the investigator
? A single area of superficial siderosis
? > 4 Cerebral micro-hemorrhages (regardless of their anatomical location or diagnostic characterization as possible” or definite”)
? Evidence of a prior macro-hemorrhage
3.Clinical evidence or Hx. of any of the following within specified period before Baseline:
? Cerebr-ovascular 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 =15 minutes (2 years)
4.Epilepsy (a single prior seizure is considered acceptable)
5.Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision (DSM IV-TR) criteria met(and not subsequently revised) for any of the following within specified period:
? Major depressive disorder (current)
? Schizophrenia (lifetime)
? Other psychotic disorders, bipolar disorder (within the past 5years), substance(including alcohol) related disorders (within the past 2 years)
6.Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging; MR compatible prosthetics, clips, stents, or any other device proven to be compatible will be allowed.
7.Resides in hospital or moderate to high dependency continuous care facility
(Residence in low grade assisted living facility where there is sufficient autonomy to permit valid evaluation of activities of daily living is permitted so long as it is not mandated by an order issued either by the judicial or the administrative authorities).
8.History of swallowing difficulties (note: study drug should be swallowed whole and MUST NOT be broken, crushed, or chewed, or dissolved in fluids prior to ingestion)
9.Pregnant or breastfeeding
10.Glucose-6-phosphate dehydrogenase (G6PD) deficiency
11.History of significant hematological abnormality or current acute or chronic clinically significant abnormality, including:
? History of hereditary or acquired met-hemoglobinemia or baseline measurement of
Met-hemoglobin(MetHb)> 2.0% (confirmed on repeat)
? History of hemoglobinopathy, myelo-dysplastic syndrome, hemolytic anemia, or
Splenectomy
? Screening hemoglobin value(confirmed upon repeat) below age/sex appropriate lower limit of the central laboratory normal range.
- Subjects in whom Folate is < 4.0 ng/mL may be entered into the study provided folate supplementation(approximately 1 mg/day) is initiated and maintained for the duration of the
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary Efficacy Endpoints: ADAS-Cog11(Alzheimer’s Disease Assessment Scale-Cognitive Subscale), ADCS-CGIC(Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change) ;Safety/Tolerability: Adverse Event,Laboratory tests of blood and urine,Pulse co-oxymetry(MetHemoglobin),Vital signs,ECG,Physical/neurological examinations,Columbia-Suicide Severity Rating(C-SSRS);Safety/Tolerability: Serotonin Toxicity assessment;Safety/Tolerability: Body weight
- Secondary Outcome Measures
Name Time Method Secondary Efficacy Endpoints: ADCS-ADL23(Alzheimer’s Disease Cooperative Study-Activities of Daily Living);Secondary Efficacy Endpoints: MMSE(Mini-Mental Status Examination);Exploratory Endpoints :Reduction in glucose uptake decline by FDG-PET of the temporal lobe;Exploratory Endpoints : Whole Brain volume by MRI;Exploratory Endpoints: RUD(Resource Utilization in Dementia Questionnaire-lite