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

• Sponsor: TauRx Therapeutics Ltd (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01626391
• Collaborator: (none)
• Enrollment: 9
• Locations: 12
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: TRx0237; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TRx0237	Drug: TRx0237; TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks
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.

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of TRx0237 When Coadministered With an Acetylcholinesterase Inhibitor (AChEI) and/or Memantine [8 weeks]

   This was assessed by the number of participants who experienced adverse events within each treatment group (TRx0237 versus placebo) during 8 weeks of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Achim		Germany
2		Berlin		Germany
3		Leipzig		Germany
4		München		Germany
5		Birmingham		United Kingdom
6		Bradford		United Kingdom
7		Crowborough		United Kingdom
8		Duston		United Kingdom
9		Oxford		United Kingdom
10		Sheffield		United Kingdom
11		St Leonards on Sea		United Kingdom
12		Staffordshire		United Kingdom

Sponsors and Collaborators

• TauRx Therapeutics Ltd

Investigators

• Principal Investigator: Mark Dale, MD, MAC Clinical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TauRx Therapeutics Ltd
• ClinicalTrials.gov Identifier: NCT01626391
• Other Study ID Numbers: TRx-237-008
• First Posted: Jun 22, 2012
• Last Update Posted: Jul 11, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by TauRx Therapeutics Ltd: Alzheimer's Disease; TRx0237; Safety Study; AD
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Arm/Group Title	TRx0237	Placebo
Arm/Group Description	One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237)	One placebo tablet containing 4-mg TRx0237 administered twice daily (8 mg/day TRx0237)
Period Title: Overall Study
STARTED	5	4
COMPLETED	3	4
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	TRx0237	Placebo	Total
Arm/Group Description	One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237)	One placebo tablet containing 4-mg TRx0237 administered twice daily (8 mg/day TRx0237)	Total of all reporting groups
Overall Participants	5	4	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.2 (8.7)	74.3 (3.3)	74.2 (6.5)
Sex: Female, Male (Count of Participants)
Female	3 60%	2 50%	5 55.6%
Male	2 40%	2 50%	4 44.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	4 100%	9 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	4 100%	9 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	5 100%	4 100%	9 100%
Anti-dementia Therapy (participants) [Number]
AChEI	5 100%	4 100%	9 100%
Memantine	0 0%	0 0%	0 0%
Both	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	TRx0237	Placebo
Arm/Group Description	One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237)	One placebo tablet containing 4-mg TRx0237 administered twice daily (8 mg/day TRx0237)
Measure Participants	5	4
Number [participants]	4 80%	4 100%

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	At every visit, each subject was asked if he or she has experienced any adverse events and safety evaluations (including vital signs, clinical laboratory tests, pulse co-oximetry, 12-lead ECGs, physical and neurological evaluations, Columbia Suicide Severity Rating Scale and serotonin syndrome assessments) were performed throughout the study
Arm/Group Title	TRx0237		Placebo
Arm/Group Description	One 125-mg TRx0237 tablet administered twice daily (250 mg/day TRx0237)		One placebo tablet containing 4-mg TRx0237 administered twice daily (8 mg/day TRx0237)
All Cause Mortality
	TRx0237		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TRx0237		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	TRx0237		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		4/4 (100%)
Gastrointestinal disorders
Dyspepsia	0/5 (0%)		1/4 (25%)
Retching	0/5 (0%)		1/4 (25%)
Vomiting	0/5 (0%)		1/4 (25%)
Infections and infestations
Lower respiratory tract infection	0/5 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Fall	0/5 (0%)		1/4 (25%)
Investigations
Urobilinogen urine increased	0/5 (0%)		1/4 (25%)
Electrocardiogram QT prolonged	1/5 (20%)		0/4 (0%)
Troponin I increased	1/5 (20%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Neck Pain	0/5 (0%)		1/4 (25%)
Pain in Extremity	0/5 (0%)		1/4 (25%)
Nervous system disorders
Dizziness	0/5 (0%)		1/4 (25%)
Headache	0/5 (0%)		1/4 (25%)
Psychiatric disorders
Depression	1/5 (20%)		0/4 (0%)
Intentional self-injury	1/5 (20%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		1/4 (25%)
Wheezing	0/5 (0%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Hair colour changes	1/5 (20%)		0/4 (0%)
Surgical and medical procedures
Tooth repair	1/5 (20%)		0/4 (0%)
Vascular disorders
Hypertension	0/5 (0%)		1/4 (25%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.