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Trial registered on ANZCTR


Registration number
ACTRN12613000967785
Ethics application status
Approved
Date submitted
8/07/2013
Date registered
30/08/2013
Date last updated
6/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of F03 in Patients with Mild Cognitive Impairment due to Alzheimer's Disease
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Sequential Cohort, Multi-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of F03 in Subjects with Mild Cognitive Impairment due to Alzheimer's Disease
Secondary ID [1] 282753 0
Buck Institute for Research on Ageing F03-C-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment due to Alzheimer's Disease 289488 0
Condition category
Condition code
Neurological 289815 289815 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational medicinal product (study medication) is F03 and the comparator is F03- matching placebo. F03 will be in the form of capsules in 5 mg strength.
Dose administered in each cohort will be as follows:
Cohort 1: F03 5mg or placebo once daily
Cohort 2: F03 5mg or placebo twice daily
Duration of administration: 8 weeks.
Mode of administration: oral capsule
Adherence of study drug administration will be checked at each visit (Baseline, Weeks 1, 2, 4, 6 and 8) through the study diary cards that the participants are required to complete and study medication returns.
Intervention code [1] 287419 0
Treatment: Drugs
Comparator / control treatment
placebo - lactose capsule
Control group
Placebo

Outcomes
Primary outcome [1] 289904 0
Safety and tolerability assessment variables through adverse events, vital signs, ECGs and clinical laboratory tests including hematology, clinical chemistry and urinalysis.
Known/possible adverse events with F03 are temporary headache and constipation. Other, less common side effects have been reported and these include dizziness, fatigue, sleepiness, and gastrointestinal disorders, such as abdominal pain, diarrhoea and loss of appetite.
Timepoint [1] 289904 0
Comparison from baseline and at each visit (Weeks 1, 2, 4, 6, 8, 10 and 12)
Primary outcome [2] 290367 0
Changes in plasma F03 pharmacokinetics through the study.
Timepoint [2] 290367 0
Comparison from Baseline and at Week 4 and Week 8.
Secondary outcome [1] 303527 0
The change from baseline in CSF pharmacokinetics of F03 at Day 56 (nominal Week 8) through CSF fluid obtained through a lumbar puncture.
Timepoint [1] 303527 0
Comparison of baseline and Week 8.
Secondary outcome [2] 304362 0
The change from baseline in CSF biomarker pharmacodynamics measurements at Day 56 (nominal Week 8) through CSF fluid obtained through a lumbar puncture.
Timepoint [2] 304362 0
Comparison of baseline and Week 8.
Secondary outcome [3] 304363 0
The change from baseline in the cognitive assessments at Day 56 (nominal Week 8). For subjects who do not have an evaluation at Day 56, the evaluation at Day 28 will be carried forward and used for these analyses. The following assessments will be carried out: The California Verbal Learning Test – Second Edition, The Wechsler Memory Scale Revised (Logical Memory I and II), Trail Making Tests (A and B), The Category Verbal Fluency Test and CGIC-MCI (Clinical Global Impression of Change).
Timepoint [3] 304363 0
Comparison from baseline and Week 8 or Week 4, if Week 8 did not occur.

Eligibility
Key inclusion criteria
- Be male or a postmenopausal female and be > or = 50 to < or = 75 years of age at screening
- Have a diagnosis of Mild Cognitive Impairment (MCI) due to Alzheimer’s Disease (AD) consistent with the criteria established by Petersen et al (1999) and the 2011 recommendations from the National Institute of Aging-Alzheimer’s Association workgroups within six (6) months of the screening visit based on:
a. A memory complaint verified by an informant (e.g. study partner)
b. Mini Mental State Examination score between 24 and 30 (inclusive)
c. A Clinical Dementia Rating score of at least 0.5 (Memory Box score of 0.5 or 1 and no other Box score greater than 1)
d. Impairment in one or more memory cognitive domains (greater than would be expected for the subject’s age and educational background) as demonstrated by impaired performance in one or both of the following:
a. A total learning raw or delayed free recall (five learning trials) score of a 16- item California Verbal Learning Test-Second Edition (CVLT-II) lower than 1.5 standard deviations (SD) of the corresponding age- and education- adjusted mean score in healthy aged people (Delis et al., 2000);
b. Impaired delayed recall score on one paragraph from the Wechsler Memory Scale Revised - Logical Memory II (Weschler, 1997), below an education- adjusted norm defined as follows:
a. < or = 8, for 16 or more years of education
b. < or = 4, for 8-15 years of education
c. < or = 2, for 0-7 years of education
e. General cognition and functional performance sufficiently preserved (activities of daily living (ADL) score of 6/6 or instrumental activities of daily living (IADL) score > or = 15/17) so that a diagnosis of AD cannot be made, as assessed by the Investigator
f. Absence of dementia, as verified by clinical judgment that the patient(s) does not meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association criteria
- Have a 3T MRI showing volumetric loss in the entorrhinal cortex and hippocampus and consistent with a diagnosis of MCI due to AD
- Have a reliable study partner (informant) who agrees to monitor administration of study drug, who can accompany the subject to all study visits and who is able to provide an independent evaluation of function
- Be willing and able to undergo all test procedures including two (2) lumbar punctures and ApoE and CYP2D6 assessments
- Voluntarily sign and date an informed consent agreement approved by the Human Research Ethics Committee (HREC).
Minimum age
50 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have received prescribed medical therapies for MCI due to AD within the three (3) months prior to the first dose of study drug or plan to use any of these medical therapies at any time during the study
- Have a history of angina, congestive heart failure, cardiac arrhythmias or any other cardiac disease requiring ongoing treatment
- Have a clinically significant ECG abnormality in the opinion of the investigator, have a history of cardiac QTc interval prolongation or are taking any medications known to prolong the QTc interval unless these can be stopped for at least five (5) half-lives prior to the first dose of study drug
- Have any significant neurologic disease other than MCI due to AD (including stroke, Parkinson's disease, seizure disorder, history of significant head trauma followed by persistent neurologic deficits, known structural brain abnormalities, major depression or bipolar disorder, schizophrenia), and specifically:
i. Have significant cerebral vascular disease, as indicated by a modified Hachinski score of greater than 4
ii. Have depression, as indicated by a Hamilton Depression Rating Scale score of more than 12
- Have a history of alcohol abuse, substance abuse or dependence within two (2) years of study screening
- Have psychotic features, agitation or behavioral problems within three (3) months of study screening
- Have any of the following:
a. uncontrolled hypertension, as determined by the investigator;
b. insulin-dependent diabetes mellitus;
c. clinically significant abnormalities of renal function (serum creatinine >2 times upper limit of normal) or hepatic function (AST, ALT >2 times upper limit of normal);
d. known active hepatitis B or C;
e. known immune deficiency disease or be positive for human immunodeficiency virus (HIV)
- Received or have a requirement during the study for any of the following:
a. systemic corticosteroids within two (2) months prior to screening;
b. medications with significant cholinergic or anticholinergic side effects (e.g. tacrine, donepezil, pyridostigmine, tricyclic antidepressants, meclizine, and oxybutynin) within four (4) weeks prior to screening;
c. anticonvulsants (e.g. phenytoin, phenobarbital, carbamazepine) within two (2) months prior to screening;
d. anticoagulant therapy e.g. warfarin within four (4) weeks prior to screening;
e. narcotic analgesics within one (1) week prior to screening (excludes over-the-counter formulations such as paracetamol/codeine);
f. antipsychotics, psychostimulants, antidepressants;
g. 5-HT3 receptor antagonists within two (2) weeks prior to screening;
h. Immunotherapy e.g. monoclonal antibodies within three (3 months) prior to screening
- Are taking medications that are known to inhibit CYP2D6
- Are actively using or have used within 12 months prior to screening tobacco- or nicotine-containing products

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study will be stratified by Centre only and a randomisation list will be prepared for each centre. A randomised block design will be used for each randomisation list. The randomisation number will be used for the medication kits and the numbering system for the case report form. An independent statistician will be assigned to prepare the final randomisation list.
This study is double - blind; therefore the Sponsor personnel, Investigator, site staff and patient will not know which treatment has been assigned.
If an emergency treatment code break is required then the Sponsors Medical Monitor and the site pharmacist will have access to the treatment assignment for each randomisation number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent statistician will be assigned to prepare the final randomisation list. The randomisation list will be produced by using a randomisation table created by computer software (namely SAS version 9.2).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Other reasons/comments
Other reasons
inability to procure further IP
Date of first participant enrolment
Anticipated
5/10/2013
Actual
5/10/2013
Date of last participant enrolment
Anticipated
5/10/2014
Actual
5/10/2015
Date of last data collection
Anticipated
14/12/2016
Actual
14/12/2016
Sample size
Target
36
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 1177 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [2] 1178 0
Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 7023 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 7024 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 287524 0
Commercial sector/Industry
Name [1] 287524 0
Southern Star Research Pty Ltd
Country [1] 287524 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Southern Star Research Pty Ltd
Address
Suite 501, 7-9 Merriwa St, Gordon, NSW 2072
Country
Australia
Secondary sponsor category [1] 286269 0
None
Name [1] 286269 0
Address [1] 286269 0
Country [1] 286269 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289500 0
Bellberry Limited
Ethics committee address [1] 289500 0
229 Greenhill Road
Dulwich, SA 5065
Ethics committee country [1] 289500 0
Australia
Date submitted for ethics approval [1] 289500 0
28/06/2013
Approval date [1] 289500 0
28/06/2015
Ethics approval number [1] 289500 0
2013-06-312
Ethics committee name [2] 289515 0
Austin Health Human Research Ethics Committee
Ethics committee address [2] 289515 0
Office for Research
Level 6 HSB Austin Health
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [2] 289515 0
Australia
Date submitted for ethics approval [2] 289515 0
Approval date [2] 289515 0
28/12/2016
Ethics approval number [2] 289515 0

Summary
Brief summary
The purpose of this study is to assess safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of F03 in subjects with mild cognitive impairment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41098 0
A/Prof Roger Clarnette
Address 41098 0
McCusker Alzheimer's Research Foundation Inc.
Monash Ave
Nedlands WA 6009
Country 41098 0
Australia
Phone 41098 0
+61893474200
Fax 41098 0
Email 41098 0
info@alzheimers.com.au
Contact person for public queries
Name 41099 0
Mrs Tracey Frear
Address 41099 0
Southern Star Research
PO Box 52
Gordon NSW 2072
Country 41099 0
Australia
Phone 41099 0
+61290116266
Fax 41099 0
Email 41099 0
info@southernstarresearch.com
Contact person for scientific queries
Name 41100 0
Mr Stelios Tzannis
Address 41100 0
The Buck Institute for Research on Aging
8001 Redwood Blvd
Novato, CA 94945
Country 41100 0
United States of America
Phone 41100 0
+1415-209-2000
Fax 41100 0
Email 41100 0
info@buckinstitute.org

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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