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

Phase 3

Completed

• Conditions: Alzheimer's Disease
• Interventions: Drug: TRx0237 250 mg/day; Drug: TRx0237 150 mg/day; Drug: Placebo

• Registration Number: NCT01689246
• 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 to moderate Alzheimer's Disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-14
• Study First Submitted QC: 2012-09-20
• Study First Posted: 2012-09-21
• Study Start: 2013-01
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2018-03
• Disposition First Submitted: 2018-03-12
• Disposition First Submitted QC: 2018-03-12
• Last Update Submitted: 2018-03-12
• Disposition First Posted: 2018-03-14
• Last Update Posted: 2018-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 891

Inclusion Criteria

• Diagnosis of all cause dementia and probable Alzheimer's disease
• Clinical Dementia Rating (CDR) total score of 1 (mild) to 2 (moderate) and MMSE score of 14-26 (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, or 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:

  • 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 about methemoglobinemia at approved doses

• Current or prior participation in a clinical trial as follows:

  • Clinical trial of a product for cognition within 3 months of Screening (unless confirmed to have been randomized to placebo)
  • A clinical trial of a drug, biologic, therapeutic 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 250 mg/day	TRx0237 250 mg/day	-
TRx0237 150 mg/day	TRx0237 150 mg/day	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	65 weeks
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	65 weeks
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes	65 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 suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity

Secondary Outcome Measures

Name	Time	Method
Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	65 weeks
Change from Baseline on Mini-Mental Status Examination (MMSE)	65 weeks
Change in expected decline of whole brain volume as measured by brain MRI	39 weeks and 65 weeks

Trial Locations

Locations (117)

Xenoscience, Inc/ 21st Century Neurology; 🇺🇸 Phoenix, Arizona, United States

Feldman, Robert MD; 🇺🇸 Laguna Hills, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Shankle Clinic and Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Pacific Research Network; 🇺🇸 San Diego, California, United States

San Francisco Clinical Research Center; 🇺🇸 San Francisco, California, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

JEM Research; 🇺🇸 Atlantis, Florida, United States

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

CNS Healthcare, Inc; 🇺🇸 Jacksonville, Florida, United States

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