Safety Study of TRx0237 in Patients Already Taking Medications for Mild and Moderate Alzheimer's Disease

A Double-Blind, Placebo-Controlled, Randomised, 4-Week Safety and Tolerability Study of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease on Pre-Existing Stable Acetylcholinesterase Inhibitor and/or Memantine Therapy

The primary purpose of this study is to assess the safety and tolerability of TRx0237 when taken at the same time as acetylcholinesterase inhibitors (i.e., donepezil, galantamine, or rivastigmine) and / or memantine to treat patients with mild to moderate Alzheimer's Disease.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: TRx0237; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Achim, Germany
  • Berlin, Germany
  • Leipzig, Germany
  • München, Germany
• United Kingdom
  • Birmingham, United Kingdom
  • Bradford, United Kingdom
  • Crowborough, United Kingdom
  • Duston, United Kingdom
  • Oxford, United Kingdom
  • Sheffield, United Kingdom
  • St Leonards on Sea, United Kingdom
  • Staffordshire, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Clinical diagnosis of all cause dementia and probable Alzheimer's disease (AD)
• Mini-Mental State Examination (MMSE) score of 14-26 (inclusive)
• Cognitive impairment present for at least 6 months
• Age ≤90 years
• Modified Hachinski ischaemic score of ≤4
• Females, if of childbearing potential, must use adequate contraception and maintain this use throughout participation in the study
• Patient is able to read, understand, and provide written informed consent
• 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
• Currently taking an taking an acetylcholinesterase inhibitor and/or memantine; 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 disorder other than Alzheimer's disease
• Patients in whom baseline MRI is contraindicated such as metal implants in head (except dental), pacemaker, and cochlear implant
• Significant focal or intracranial pathology that would lead to a diagnosis other than probable Alzheimer's disease
• Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness
• Epilepsy
• Major depressive disorder, schizophrenia or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders
• Resides in a hospital or continuous care facility
• History of swallowing difficulties
• Pregnant or breastfeeding
• 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
• Pre-existing or current signs or symptoms of respiratory failure
• Concurrent acute or chronic clinically significant immunologic, renal, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease
• Prior intolerance to methylthioninium-containing drug or any of the excipients

• Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted):

  • Tacrine
  • Anxiolytics and/or sedatives/hypnotics (exceptions: sedation for MRI or occasional short-acting benzodiazepines, chloral hydrate, or zolpidem as needed at bedtime)
  • Antipsychotics (clozapine, chlorpromazine, thioridazine, or ziprasidone)
  • Carbamazepine
  • Drugs associated with methaemoglobinaemia (e.g., dapsone, local anesthetics such as benzocaine used chronically, primaquine and related antimalarials, sulfonamides)
  • Warfarin (and other Coumadin derivates such as phenprocoumon)
• Current or prior participation in a clinical trial of a drug, biologic, or device in which the last dose was received within 28 days prior to Baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablets will be administered twice daily (b.i.d.) for 4 weeks. The placebo tablets include 4 mg of TRx0237 as a urinary and faecal colourant to maintain blinding; hence, the placebo group will receive a total of 8 mg/day of TRx0237.
Experimental: TRx0237	Drug: TRx0237; TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine	This was assessed by the number of participants who experienced adverse events within each treatment group (TRx0237 versus placebo) during 8 weeks of treatment.	8 weeks

Collaborators and Investigators

• Sponsor: TauRx Therapeutics Ltd
• Investigators: Principal Investigator: Mark Dale, MD, MAC Clinical Research

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (Estimate): June 22, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2014
• Last Update Submitted That Met QC Criteria: June 10, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; AD; TRx0237; Safety Study
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: TRx-237-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No