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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02727699




Registration number
NCT02727699
Ethics application status
Date submitted
21/03/2016
Date registered
5/04/2016
Date last updated
6/05/2021

Titles & IDs
Public title
A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu)
Scientific title
XanADu: A Phase II, Double-Blind, 12-Week, Randomised, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to Alzheimer's Disease (AD)
Secondary ID [1] 0 0
ACW0002
Universal Trial Number (UTN)
Trial acronym
XanADu
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia, Alzheimer Type 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Xanamem™
Treatment: Drugs - Placebo (for Xanamem™)

Experimental: Xanamem™ - Oral Xanamem™ capsules 10mg, to be administered once daily

Placebo Comparator: Placebo - Matching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily


Treatment: Drugs: Xanamem™
Xanamem™ is formulated in green and cream coloured size 3, Coni-Snap shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains active pharmaceutical ingredient of UE2343

Treatment: Drugs: Placebo (for Xanamem™)
Excipient blend capsules manufactured to mimic Xanamem™ capsules

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ADAS-Cog v14 - Change in Alzheimer's Disease Assessment Scales - Cognitive Subscale Score, version 14 (ADAS-Cog v14) Total scores of ADAS Cog 14 range from 0 to 90, with higher scores indicating greater disease severity.
Timepoint [1] 0 0
Baseline, Week 12
Primary outcome [2] 0 0
AD COMposite Scores - Change in AD COMposite Scores (ADCOMs- ADCOMs, composite score is derived from a weighted linear combination of items from commonly used outcome scales Cognitive Subscale Version 14 [ADAS-Cog v14], Clinical Dementia Rating Scale - Sum of Boxes [CDR-SOB], and Mini-Mental Status Examination [MMSE]. Th ADCOMs range: 0 - 1.97, whereas a lover score is interpreted as a better result.
Included scales:
ADAS-Cog v14 (range: 0-90): A lower score is indicative of better cognition, a higher score indicates higher cognitive impairment.
CDR-SUB (range: 0-18): A lower score is indicative of better cognition, a higher score indicates higher cognitive impairment.
MMSE (range: 0-30): A higher score is indicative of better cognition, a lower score indicates higher cognitive impairment.
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [1] 0 0
RAVLT - Change in Rey Auditory Verbal Learning Test (RAVLT) RAVLT will be administered using five trials, with individual scores from 0-15. The total score is the combined score of all five trials, ranging from 0 to 75, whereas a lower score is considered a worse outcome and a higher score a better outcome.
Timepoint [1] 0 0
Baseline, Week 12
Secondary outcome [2] 0 0
CDR-SOB - Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) The CDR is obtained through semi-structured interviews of patients and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care.
Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment.
The CDR-SOB is based on summing each of the domain box scores, with scores ranging from 0-18, whereas lower scores represent better outcomes and higher scores worse outcomes.
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
MMSE - Change in Mini-Mental Status Examination (MMSE) MMSE total score (0 - 30) is a sum of all 30 point questionnaire of MMSE. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia.
Timepoint [3] 0 0
Baseline, Week 12
Secondary outcome [4] 0 0
NPI (Neuropsychiatric Inventory) - Change in Neuropsychiatric Inventory (NPI) The NPI includes questions to ten behavioural and two neurodegenerative domains.
Raters recorded neuropsychiatric symptoms using a 1-4 scale for frequency and a 1-3 scale for severity for each item in the instrument, with the score for each domain being: domain score = frequency x severity.
The total score is calculated by adding the scores of the first 10 domain scores.
The two neurodegenerative items are not included in the NPI total score as they form part of the depression syndrome in some patients and were specifically excluded from the dysphoria subscale of the NPI in order to allow that subscale to focus on mood symptoms.
The total NPI-score minimum is 0 and the maximum 144. A lower score is considered a better outcome, a higher score a worse outcome.
Timepoint [4] 0 0
Baseline, Week 12
Secondary outcome [5] 0 0
NTB - Executive Domain - Change in Neuropsychological Test Batteries (NTB) - Executive Domains: Controlled Oral Word Association - Test (COWAT) and Total Correct Response (CFT) Total NTB score is the sum of COWAT and CFT. During the COWAT test, the subject is asked to mention as many words as possible beginning with different letters (F, A, S) within 1 minute each. The number of words for each letter is recorded, the score is the sum of all words. There is no minimum or maximum score, whereas more words indicate a better outcome.
During the CFT test, the subject is given 1 minute to produce as many unique words as possible within a semantic category. The subject's score is the number of unique correct words.
There is no minimum or maximum score whereas a score of under 14 is interpreted as concerning regarding cognition.
Timepoint [5] 0 0
Baseline, Week 12

Eligibility
Key inclusion criteria
1. Males and females aged 50 years or older at the time of informed consent.

2. Female Subjects:

1. Post menopausal women, defined as no menses for 12 months without an alternative
medical cause. If there is any concern about the menopausal status of a
prospective female subject, a follicle stimulating hormone test (FSH) should be
requested to confirm post-menopausal status. Post menopausal women confirmed by
FSH level > 40 mIU (milli-international units per milliliter) /mL, will be
confirmed by central laboratory.

2. Women of childbearing potential (WOCBP) must have a negative pregnancy test at
Screening and Baseline, and be willing to use highly effective methods of
contraception from the Screening visit until 3 months after last dose of study
drug. If re-test is required, a local urine pregnancy test will be performed at
Baseline to determine if the subject can continue to randomisation.

3. Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or
bilateral oophorectomy.

4. Women must not be breastfeeding.

3. Male Subjects:

1. Who are sexually active, fertile men must use highly effective methods of
contraception from Day 1 until 3 months after last dose of study drug if their
partners are WOCBP.

2. Who are permanently sterile or have had bilateral orchiectomy.

4. Diagnosis of mild dementia due to Alzheimer's disease (AD) with increased level of
certainty (provided by evidence of clinical deterioration within the 6 months
preceding Screening, as assessed by the investigator) as determined by the National
Institute of Ageing (NIA) and the Alzheimer's Association (AA) workgroup.

5. Mild dementia due to probable AD with MMSE (Mini-Mental Status Examination) 20 to 26
(inclusive).

6. Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.

7. A brain magnetic resonance imaging (MRI) or computed tomography (CT) scan in the 12
months preceding Screening that in the investigator's opinion is consistent with AD as
the principle aetiology of the dementia with no other clinically significant
abnormality, e.g. another principle underlying aetiology of the subject's dementia, or
a lesion which could affect cognition e.g. a brain tumour or large stroke.

8. On stable dose of acetylcholinesterase (AChEI) and/or memantine (at least 3 months
prior to Screening) OR treatment-naïve. Initiating AChEIs or memantine during the
study will not be permitted.

9. Apart from a clinical diagnosis of mild dementia due to AD, the subject must be in
good health as determined by the investigator, based on medical history and screening
assessments.

10. Has a consenting study partner who, in the investigator's judgement, has frequent and
sufficient contact with the subject to be able to provide accurate information as to
the subject's cognitive and functional abilities. The study partner must be available
to provide information to the investigator and study site staff about the subject and
agrees to attend all study site visits in person for scale completion. A study partner
should be available for the duration of the study. The measure of adequate
availability will be at the investigator's discretion.

11. Must be willing and able to comply with the requirements of the protocol and must be
available to complete the study.

12. Must satisfy a medical examiner about their fitness to participate in the study.

13. Must provide written informed consent to participate in the study.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant abnormalities in vital signs (blood pressure, heart rate,
respiration rate and oral temperature), as determined by the investigator.

2. Clinically significant abnormal haematology, biochemistry and urine examination
values, specifically abnormal liver and renal function and Vitamin B12 levels below
lower threshold since these parameters may impact cognitive function, as determined by
the investigator.

3. Has had a significant systematic illness or infection within the past 4 weeks prior to
randomisation, as determined by the investigator.

4. Clinically significant neurological disease other than AD, such as (but not limited
to) Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure
hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder,
subdural haematoma, multiple sclerosis or a history of significant head trauma
followed by persistent neurologic defaults or known structural brain abnormalities.

5. Subjects with clinical evidence of peripheral neuropathy or historical evidence of
clinically significant nerve conduction abnormalities.

6. Has had a stroke within the year prior to randomisation, as determined by the
investigator.

7. Has a lifetime diagnosis of a major psychiatric disorder (other than dementia), based
on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria.
This includes but is not limited to schizophrenia, schizoaffective disorder, bipolar
affective disorder, alcohol dependence syndrome or major depressive disorder.

8. Has a history of disease directly related to the hypothalamus, the pituitary and/or
the adrenal glands which affect the hypothalamic-pituitary-adrenal axis function.

9. Has uncontrolled clinical conditions relating to glucose and lipid metabolism.

10. Clinically significant electrocardiogram (ECG) abnormalities, including QTc (Corrected
QT interval) interval > 450 ms, following ECG tracings at Screening.

11. Use of any prohibited medication as detailed in the study protocol.

12. Participation in another clinical study of an investigational drug or device whereby
the last investigational drug/device administration is within 60 days of Screening.

13. Inability to communicate well with the investigator (i.e. language problem, non-fluent
English [as scales will be provided in English only], poor mental development or
impaired cerebral function).

14. Subject will undergo the tests, ADAS (Alzheimer's Disease Assessment Scales)-Cog v14,
CDR-SOB (Sum of Boxes), MMSE, NTB (Neuropsychological Test Battery; executive domain)
and RAVLT at the indicated time-points to avoid uncontrolled learning effects.
Subjects who need to perform these tests externally to and in parallel with this study
will be excluded.

15. Subject has ingested any food or drink containing grapefruit, Seville oranges, star
fruit or derived products (e.g. fruit juice), for at least 3 days prior to the first
administration of study drug.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Central Coast Neurosciences Research - Central Coast
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
KaRa Institute of Neurological Diseases - Macquarie Park
Recruitment hospital [4] 0 0
Medical & Cognitive Research Unit, Heidelberg Repatriation Hospital - Austin Health - Heidelberg West
Recruitment hospital [5] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2261 - Central Coast
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [4] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Combe Park
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Lancashire
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Northern Ireland
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actinogen Medical
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This XanADu Phase II study in mild Alzheimer's Disease (AD) is to assess the safety,
tolerability and efficacy of Xanamem™ in subjects with mild dementia due to Alzheimer's
Disease. Subjects will be randomized to receive either 10mg once daily Xanamem™ or Placebo at
a 1:1 ratio in a double-blinded fashion.
Trial website
https://clinicaltrials.gov/show/NCT02727699
Trial related presentations / publications
Webster SP, McBride A, Binnie M, Sooy K, Seckl JR, Andrew R, Pallin TD, Hunt HJ, Perrior TR, Ruffles VS, Ketelbey JW, Boyd A, Walker BR. Selection and early clinical evaluation of the brain-penetrant 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor UE2343 (Xanamem™). Br J Pharmacol. 2017 Mar;174(5):396-408. doi: 10.1111/bph.13699. Epub 2017 Jan 25.
Public notes

Contacts
Principal investigator
Name 0 0
Bill Ketelbey, MD
Address 0 0
Actinogen Medical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications