Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease

Phase 3

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: TRx0237 200 mg/day
Drug: Placebo

Registration Number: NCT01689233

Lead Sponsor: TauRx Therapeutics Ltd

Brief Summary: The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild Alzheimer's Disease.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 800

Inclusion Criteria

Diagnosis of all cause dementia and probable Alzheimer's disease
Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) and MMSE score of 20-26 (inclusive)
Age <90 years
Modified Hachinski ischemic score of ≤4
Females, if of child-bearing potential, must practice true abstinence or be competent to use adequate contraception and agree to maintain this throughout the study
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
Has one (or more) identified adult caregiver who 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; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug
If currently taking an acetylcholinesterase inhibitor and/or memantine at the time of Screening, 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 (CNS) disorder other than Alzheimer's disease
Significant focal or vascular intracranial pathology seen on brain MRI scan
Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes
Epilepsy
Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders
Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI
Resides in hospital or moderate to high dependency continuous care facility
History of swallowing difficulties
Pregnant or breastfeeding
Glucose-6-phosphate dehydrogenase deficiency
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
Preexisting or current signs or symptoms of respiratory failure
Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease
Diagnosis of cancer within the past 2 years prior to Baseline (other than basal cell or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted in complete freedom from disease for at least 2 years
Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar organic dyes, or any of the excipients
Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted):
- Tacrine
- Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)
- Carbamazepine, primidone
- Drugs with a warning or precaution in the labeling of methemoglobinemia at approved doses
Current or prior participation in a clinical trial as follows:
- Clinical trial of a product for cognition in which the last dose was received within 90 days prior to Screening (unless confirmed to have been randomized to placebo)
- A clinical trial of a drug, biologic, device, or medical food in which the last dose/administration was received within 28 days prior to Baseline

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRx0237 200 mg/day	TRx0237 200 mg/day	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	78 weeks
Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	78 weeks
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes	78 weeks	Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for serotonin toxicity, brain magnetic resonance imaging (MRI), and potential for suicide or self-harm.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	78 weeks
Change from Baseline in Mini-Mental Status Examination (MMSE)	78 weeks
Change from Baseline in Neuropsychiatric Inventory (NPI)	78 weeks
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)	78 weeks
Change in expected decline of whole brain volume as measured by brain MRI	78 weeks

Trial Locations

Locations (95): Xenoscience, Inc / 21st Century Neurology
🇺🇸
Phoenix, Arizona, United States
NoesisPharma Clinical Trials
🇺🇸
Phoenix, Arizona, United States
CITrials
🇺🇸
Bellflower, California, United States
ATP Clinical Research, Inc.
🇺🇸
Costa Mesa, California, United States
Southern California Research, LLC
🇺🇸
Fountain Valley, California, United States
Feldman, Robert MD
🇺🇸
Laguna Hills, California, United States
Synergy East
🇺🇸
Lemon Grove, California, United States
Collaborative Neuroscience Network
🇺🇸
Long Beach, California, United States
Neuro-Therapeutics, Inc.
🇺🇸
Pasadena, California, United States
Anderson Clinical Research
🇺🇸
Redlands, California, United States
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Xenoscience, Inc / 21st Century Neurology
🇺🇸Phoenix, Arizona, United States