A comparison study of TRx0237 and placebo in patients with mild to moderate Alzheimer's Disease

• Conditions: Alzheimer’s Disease; MedDRA version: 16.1Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2012-002866-11-BG
• Lead Sponsor: TauRx Therapeutics Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-30
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 833

Inclusion Criteria

1. Diagnosis according to the National Institute on Aging (NIA) and Alzheimer’s Association (AA) criteria of:
• All cause dementia
and
• Probable Alzheimer’s disease
2. Clinical Dementia Rating (CDR) total score of 1 (mild) to 2 (moderate) and Mini-Mental State Examination (MMSE) score of 14-26 (inclusive) at Screening
3. Age <90 years at Screening
4. Modified Hachinski ischemic score of =4 at Screening
5. Females must meet one of the following:
• Surgically sterile (hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 months minimum
• Have undergone bilateral tubal occlusion / ligation at least 6 months prior
• Post-menopausal for at least 1 year
• Using adequate contraception (a barrier method [such as condom, diaphragm or cervical/vault cap] with spermicidal foam, gel, film, cream, or suppository; intrauterine device [IUD] or system;, or oral or long-acting injected or implanted hormonal contraceptives for at least 3 months prior to Baseline; or vasectomized partner [with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate]);]) or true abstinence (when this is in line with the preferred and usual lifestyle of the subject); subjects must be competent to use adequate contraception and to agree to continue to maintain adequate contraception throughout participation in the study
OR In Italy, accept to avoid a pregnancy for at least 3 months prior to Baseline and throughout participation in the study

6. 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 in the designated language of the study site
•In Germany, subjects must be able to provide their own written informed consent
7. Has one or more identified adult caregivers who meet the following criteria:
• Either lives with the subject or sees the subject on average for = 2 hours/day = 3 days/week, or in the investigator’s opinion, the extent of contact is sufficient to provide meaningful assessment of changes in subject behavior and function over time and provide information on safety and tolerability
• 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
• Agrees to accompany the subject to each study visit
• Is able to verify daily compliance with study drug
8. If currently taking an acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, and/or memantine at the time of the Screening:
• The subject must have been taking such medication(s) for = 3 months
• The current dosage regimen and dosage form must be within the locally approved dose range and must have remained stable for = 6 weeks
• It must be planned that the dosage regimen will remain stable throughout participation in the study
Subjects not being treated with an AChEI or memantine (for = 6 weeks before Screening) may also be enrolled if initiation of an AChEI or memantine is not planned for the time period during which the subject will be participating in this study
9. Able to comply with the study procedures in the view of the investigator
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 333
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

Exclusion Criteria

1.Significant CNS disorder other than Alzheimer’s disease
2.Significant intracranial focal or vascular pathology seen on brain MRI scan within a maximum of 42 days before Baseline that would lead to a diagnosis other than probable Alzheimer’s disease or that puts the subject at risk of ARIA, including: large confluent white matter hyperintense lesions, other focal brain lesion(s), a single area of superficial siderosis, >4 cerebral microhemorrhages, evidence of a prior macrohemorrhage.
3.Clinical evidence or history of any of the following within specified period before Baseline:
•Cerebrovascular accident (2 years)
•Transient ischemic attack (6 months)
•Significant head injury with associated loss of consciousness, skull fracture or persisting cognitive impairment (2 years)
•Other unexplained or recurrent loss of consciousness =15 minutes (2 years)
4.Epilepsy (a single prior seizure considered acceptable)
5.DSM IV-TR criteria met for any of the following within specified period:
•Major depressive disorder (current)
•Schizophrenia (lifetime)
•Other psychotic disorders, bipolar disorder (within past 5 years), or substance (incl. alcohol) related disorders (within past 2 years)
6.Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging; MR compatible prosthetics, clips, stents, or any other device proven to be compatible will be allowed.
7.Resides in hospital or moderate to high dependency continuous care facility.
8.History of swallowing difficulties
9.Pregnant or breastfeeding
10.G6PD deficiency
11.History of significant hematological abnormality or current acute or chronic clinically significant abnormality, including:
•History of hereditary or acquired methemoglobinemia or baseline measurement of MetHb >2.0%
•History of hemoglobinopathy, myelodysplastic syndrome, hemolytic anemia, or splenectomy
•Screening hemoglobin value below age/sex appropriate lower limit of the central laboratory normal range
12.Abnormal serum chemistry laboratory value at Screening. In addition, subjects with either of the following abnormalities must be excluded: creatinine clearance <30 mL/min at Screening and TSH above laboratory normal range (subject may be treated and rescreened after 3 months)
13.Clinically significant cardiovascular disease or abnormal assessments such as:
•Hospitalization for acute coronary syndrome or symptoms consistent with angina pectoris, within the 12 months preceding Baseline
•Signs or symptoms of clinical heart failure within the 12 months preceding Baseline
•Evidence of uncontrolled atrial fibrillation on Screening ECG or history of atrial fibrillation not currently controlled or where the QT interval cannot be assessed by triplicate ECGs
•QTcF at Screening >460 msec in males or >470 msec in females, or low or flat T waves making measurement of QT interval unreliable
•Recent history of poorly controlled hypertension, systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg, at Screening
•Hypotension: systolic blood pressure <100 mmHg at Screening
•Heart rate <48 bpm or >96 bpm by measurement of vital signs or by ECG at Screening
14.Preexisting or current signs or symptoms of respiratory failure. Subjects with previously diagnosed moderate to severe sleep apnea not adequately controlled should be excluded.
15.Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified