A 12-Week randomised, double-blind, placebo-controlled, parallel three-group study to assess the safety, tolerability and efficacy of two dose levels of PBT2 to slow progression of disease in patients with early Alzheimer’s disease

Conditions: Patients with early AD
MedDRA version: 8.1Level: LLTClassification code 10001896Term: Alzheimer's disease

Registration Number: EUCTR2006-002527-17-SE

Lead Sponsor: Prana Biotechnology

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

1.Fulfil National Institute of Neurological and Communication Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) criteria for probable AD and International Classification of Diseases (ICD)-10 criteria for AD.
2.Community dwelling
3.Age over 55 years
4.Female patients must be surgically sterile or post-menopausal (as confirmed by FSH levels at screening)
5.Mini-mental Status Examination (MMSE) score between 20 and 26 inclusive consistent with early AD or ADAS-Cog score of 10-25. Both scores must be consistent with early AD.
6.Stable medical condition for 3 months prior to screening
7.Physically/medically stable as confirmed by medical history, physical exam, neurological exam, and clinical laboratory tests
8.Supervision available for administration of study medications
9.Sufficient command of written Swedish to complete patient questionnaires
10.Modified Hachinski = 4
11.Computerised tomography (CT) or magnetic resonance imaging (MRI) scan within the last 24 months which, in the opinion of the local investigator, does not alter the diagnosis of AD to vascular or multi-infarct dementia.
12.Able to complete baseline assessments
13.Able to ingest oral medication
14.Stable dose of donepezil, rivastigmine
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Allergy to PBT2 or its excipients (lactose, povidone)
2.Evidence (in the opinion of the investigator) of any other form of dementia with particular reference to the NINDS-AIREN (Vascular), Lund and Manchester (FTD) or McKeith (DLBD) Consensus Guidelines
3.Diagnosis of Parkinson’s Disease
4.History or clinical evidence of peripheral neuropathy
5.History of optic neuritis or diagnosed age-related macular degeneration
6.History of clinically significant stroke
7.Current evidence or history in the past 2 years of seizures, head injury with loss of consciousness and/or immediate confusion after the injury
8.Neoplasm currently active or likely to recur (except basal cell carcinoma)
9.Any untreated medical condition which may increase the risk of peripheral neuropathy or optic neuritis
10.Abnormal liver function tests (twice the upper limit cited in reference range)
11.Creatinine clearance less than 60% of reference range (by plasma Creatinine, sex and weight algorithm)
12.Random blood glucose greater than 50% of upper limit of normal at screening
13.Unstable thyroid dysfunction
14.Blood pressure > 180mmHg systolic or > 98mmHg diastolic on three separate occasions during the screening period.
15.Clinically significant (i.e. requiring medical intervention) anaemia
16.Any current, unstable, clinically relevant haematological or biochemical disorder
17.Confirmed HIV disease, Hepatitis A, B or C positive IgM – all patients will be screened for viral hepatitis (HIV testing will be done if clinically indicated)
18.Current ICD-10 criteria-based diagnosis for major psychiatric disorder including psychosis, major depression and bipolar disorder – not symptoms subsequent to AD
19.Documented past history of recurrent major psychiatric disorder. Single episodes of psychiatric illness in the past are not exclusions.
20.Alcohol or substance abuse as defined using ICD-10 criteria
21.Blindness, deafness, language difficulties or any other disability which may prevent the patient from participating or cooperating with the protocol.
22.Use of drugs with significant central anticholinergic or antihistaminic effects within 1 month of baseline or drugs with a narrow therapeutic margin which are metabolised by CYP1A2 (see Appendix A).
23.Evidence of space occupying lesion, raised intracranial pressure or any other finding that is a contraindication to performing a lumbar puncture.
24.Patients taking memantine.
25.Treatment with an investigational drug trial within 8 weeks of screening visit.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To assess the safety and tolerability of two doses of PBT2 in a population of patients suffering from early Alzheimer’s disease (AD) in order to build on extant safety data generated in Phase I testing.;Secondary Objective: •To assess the effect of two doses of PBT2 on biomarkers associated with AD (plasma and cerebrospinal fluid [CSF]) <br>•To determine the impact on specific cognitive activity associated with early AD of two doses of PBT2.<br>;Primary end point(s): Safety outcome<br><br>Biological outcomes-Change from baseline<br>-CSF markers<br>-plasma markers<br><br>Cognitive outcomes-Change from baseline<br>-Neuropsychiatric Test Battery<br>-Neuropsychiatric Inventory<br><br><br><br>

Secondary Outcome Measures