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Dementia, Alzheimer TypePhase 2XanADuNCT02727699

A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu)

A Phase 2 study testing Xanamem™ in people with Dementia, Alzheimer Type, run by Actinogen Medical at 25 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Dementia, Alzheimer Type
What is being tested?
Xanamem™
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
185 participants
Where
25 sitesin 3 countries
Study dates
23 Mar 2017to 15 Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females aged 50 years or older at the time of informed consent.
  • Female Subjects:
  • 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.
  • 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.
  • Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy.
  • Women must not be breastfeeding.
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  • Male Subjects:
  • 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.
  • Who are permanently sterile or have had bilateral orchiectomy.
  • 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.
  • Mild dementia due to probable AD with Mini-Mental Status Examination (MMSE) 20 to 26 (inclusive).
  • Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.
  • 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.
  • 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.
  • 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.
  • 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.
  • Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
  • Must satisfy a medical examiner about their fitness to participate in the study.
  • Must provide written informed consent to participate in the study.

Who cannot join

  • Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
  • 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.
  • Has had a significant systematic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator.
  • 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.
  • Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities.
  • Has had a stroke within the year prior to randomisation, as determined by the investigator.
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  • 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.
  • 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.
  • Has uncontrolled clinical conditions relating to glucose and lipid metabolism.
  • Clinically significant electrocardiogram (ECG) abnormalities, including Corrected QT interval (QTc) > 450 ms, following ECG tracings at Screening.
  • Use of any prohibited medication as detailed in the study protocol.
  • Participation in another clinical study of an investigational drug or device whereby the last investigational drug/device administration is within 60 days of Screening.
  • 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).
  • Subject will undergo the tests, Alzheimer's Disease Assessment Scales (ADAS)-Cog v14, CDR-Sum of Boxes (SOB), MMSE, Neuropsychological Test Battery (NTB; 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.
  • 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.

Trial locations and contacts

25 sites in 3 countries.

25 sites in 3 countries

United States14 sites

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • Research Alliance Inc.

    Clearwater, Florida, 33756

  • NeuroStudies.Net, LLC

    Decatur, Georgia, 30033

  • The Clinical Trial Center

    Jenkintown, Pennsylvania, 19046

  • National Research Institute

    Los Angeles, California, 90057

  • The Neurology Research Group, LLC

    Miami, Florida, 33186

  • The NeuroCognitive Institute

    Mount Arlington, New Jersey, 07856

  • Compass Research LLC

    Orlando, Florida, 32806

  • IMIC, Inc.

    Palmetto Bay, Florida, 33157

  • PCND Neuroscience Research Institute

    Poway, California, 92064

  • PMG Research of Rocky Mount, LLC

    Rocky Mount, North Carolina, 27804

  • Pacific Research Network, Inc.

    San Diego, California, 92103

  • Richmond Behavioral Associates

    Staten Island, New York, 10312

  • Tucson Neuroscience Research, LLC

    Tucson, Arizona, 85710

Other trials in United States

United Kingdom6 sites

  • The Research Institute for the Care of Older People

    Bath, Combe Park, BA1 3NG

  • Institute of Clinical Sciences, Queen's University Belfast

    Belfast, Northern Ireland, BT9 7AB

  • Centre for Clinical Brain Sciences, Centre for Dementia Prevention, The University of Edinburgh

    Edinburgh, EH8 9YL

  • West London Mental Health Trust

    Isleworth, London, TW7 6FY

  • St Pancras Clinical Research

    Kings Cross, London, WC1X 8QD

  • Manchester Mental Health & Social Care Trust - Dementia Research Office - Park House North Manchester General Hospital

    Manchester, Lancashire, M8 5RB

Other trials in United Kingdom

Australia5 sites

  • Central Coast Neurosciences Research

    Central Coast, New South Wales, 2261

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Medical & Cognitive Research Unit, Heidelberg Repatriation Hospital - Austin Health

    Heidelberg West, Victoria, 3081

  • KaRa Institute of Neurological Diseases

    Macquarie Park, New South Wales, 2113

  • Australian Alzheimer's Research Foundation

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official 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)

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.

Read the detailed description

This is a Phase II, randomised, multi-centre, double-blind, placebo-controlled proof-of-concept study to assess the safety, tolerability and efficacy of oral Xanamem once daily in adult subjects with mild dementia due to AD.

Based on Xanamem's mode of action on hippocampal function, amnestic symptoms may respond best, thus favouring the inclusion of mild dementia due to AD, with given evidence of disease progression. Subjects will be treated in a double-blind fashion, where both the investigators and subjects will be unaware of the treatment assignments, to minimise any subjective or unrecognised bias carried by the investigators and subjects. Placebo will be used as the comparator in this study.

It is planned to randomise approximately 174 subjects at approximately 25 study sites in three countries (Australia, United Kingdom, and United States), with the aim to enrol 7 to 10 subjects at each study site. Subject enrolment will be competitive but a cap of 20 subjects per study site is to be established to avoid any side effects. In case the sample composition at one study site is creating concerns, an enrolment stop can also occur at fewer than 20 subjects.

At study end, a total of 185 subjects were randomised into this study and received active treatment.

The data safety monitoring board (DSMB) will periodically meet for the review of accumulating safety study data and will also be involved in the interim analysis.

At the Baseline visit (Week 0), eligible subjects will be randomised on a 1:1 ratio to receive either Xanamem administered orally once daily (QD) for the treatment group or matching placebo for the placebo group. Subjects will return to the study site for visits at Week 4 and Week 8, End of Treatment (Week 12) and Follow-up (4 weeks post last dose of study drug) visits, at which study assessments will be performed.

Ad hoc telephone contact may also occur at any other time-point throughout the study, if deemed necessary by the investigator/study nurse, or if the subject wishes to report an Adverse Event (AE)

Subjects will be interviewed and examined at the study site at each visit and will complete a variety of questionnaires and routine safety evaluations.

Optional Pharmacodynamic (PD) sampling will be performed at specific visits. Subjects who do not provide consent for this optional sub-study will still be eligible for the main study.

The overall study duration for an individual subject will be 17 to 20 weeks, including a screening period of one to 4 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 4 weeks. The total duration of the study is expected to be 2 years.

Being tested
Xanamem™, Placebo (for Xanamem™)
Keywords
Dementia, Alzheimer's Disease, Xanamem, UE2343 (Laboratory Code for Xanamem), Cortisol, XanADu, Actinogen, 11β-HSD1, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Mild Alzheimer's Disease, Cognitive Impairments, emestedastat
Medical subject headings
Alzheimer Disease, Dementia, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Xanamem™Drug

    Also called UE2343

    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

  • Placebo (for Xanamem™)Drug

    Also called Placebo

    Excipient blend capsules manufactured to mimic Xanamem™ capsules

Study groups in NCT02727699
Study groupRoleWhat they receive
Xanamem™ExperimentalOral Xanamem™ capsules 10mg, to be administered once daily
Receives: Drug: Xanamem™
PlaceboPlacebo comparatorMatching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily
Receives: Drug: Placebo (for Xanamem™)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, Week 12

  2. 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-SOB (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.

    Measured: Baseline, Week 12

Secondary outcomes (5)

  1. 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.

    Measured: Baseline, Week 12

  2. 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.

    Measured: Baseline, Week 12

  3. 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.

    Measured: Baseline, Week 12

  4. 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.

    Measured: Baseline, Week 12

  5. 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.

    Measured: Baseline, Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2016 (estimated)
  2. Study start23 Mar 2017
  3. Primary completion15 Mar 2019
  4. Study completion15 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
185 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02727699
Sponsor's protocol ID
ACW0002
Acronym
XanADu
Status last verified
Apr 2022
First submitted
21 Mar 2016
Last updated
3 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor UE2343 (Xanamem). Br J Pharmacol. 2017 Mar;174(5):396-408. doi: 10.1111/bph.13699. Epub 2017 Jan 25.

    PubMed 28012176

  • Taylor J, Jaros M, Chen C, Harrison J, Hilt D. Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11beta-HSD1 Inhibitor Xanamem(R) for Mild Alzheimer's Disease. J Alzheimers Dis. 2024;100(1):139-150. doi: 10.3233/JAD-231456.

    PubMed 38848180

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Xanamem™ in people with Dementia, Alzheimer Type, run by Actinogen Medical at 25 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ADAS-Cog v14 (time frame: Baseline, Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02727699, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.

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