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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by TauRx Therapeutics Ltd
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01689246
First received: September 14, 2012
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: TRx0237 150 mg/day
Drug: TRx0237 250 mg/day
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 15-Month Trial of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by TauRx Therapeutics Ltd:

Primary Outcome Measures:
  • Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 65 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [ Time Frame: 39 weeks and 65 weeks ] [ Designated as safety issue: No ]
  • Change in expected decline of whole brain volume as measured by brain MRI [ Time Frame: 39 weeks and 65 weeks ] [ Designated as safety issue: No ]
  • Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 833
Study Start Date: February 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRx0237 250 mg/day Drug: TRx0237 250 mg/day
TRx0237 125 mg tablets will be administered twice daily.
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets will be administered twice daily. The active placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence the placebo group will receive a total of 8 mg/day of TRx0237.
Experimental: TRx0237 150 mg/day Drug: TRx0237 150 mg/day
TRx0237 75 mg tablets will be administered twice daily.

  Eligibility

Ages Eligible for Study:   up to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

    • Clinical trial of a product for cognition within 3 months (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01689246

Contacts
Contact: Karen Pozzie 1-800-910-5609 info@alzheimersstudies.net

  Show 126 Study Locations
Sponsors and Collaborators
TauRx Therapeutics Ltd
  More Information

Additional Information:
No publications provided

Responsible Party: TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT01689246     History of Changes
Other Study ID Numbers: TRx-237-015
Study First Received: September 14, 2012
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan : Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by TauRx Therapeutics Ltd:
Alzheimer's Disease
Alzheimer Disease
TRx0237
AD
Neurodegenerative Diseases
Dementia
Brain Diseases

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 28, 2014