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

NCT02727699 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ACW0002
• Study Type: interventional
• Target: 185
• Locations: 3 countries
• Sites: 25

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.

Conditions

Dementia, Alzheimer Type

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, Week 12

• 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.

  Baseline, Week 12

Secondary Outcomes (5)

• RAVLT

  Baseline, Week 12

• CDR-SOB

  Baseline, Week 12

• MMSE

  Baseline, Week 12

• NPI (Neuropsychiatric Inventory)

  Baseline, Week 12

• NTB - Executive Domain

  Baseline, Week 12

Other Outcomes (14)

• Pregnancy Test

  Screening, baseline, Week 4, Week, 8, Week 12, Week 16

• Optional PD Assessment - Changes in Pharmacodynamic (PD) Measures of Testosterone

  Screening, baseline, Week 4, Week, 8, Week 12, Week 16

• Optional PD Assessment - Changes in Pharmacodynamic (PD) Measures of Androstenedione

  Screening, baseline, Week 4, Week, 8, Week 12, Week 16

Study Arms (2)

Xanamem™

EXPERIMENTAL

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

Drug: Xanamem™

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo (for Xanamem™)

Interventions

Xanamem™ DRUG

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

Also known as: UE2343

Xanamem™

Placebo (for Xanamem™) DRUG

Excipient blend capsules manufactured to mimic Xanamem™ capsules

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Actinogen Medical: lead
• ICON Clinical Research: collaborator

Study Sites (25)

Tucson Neuroscience Research, LLC

Tucson, Arizona, 85710, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

PCND Neuroscience Research Institute

Poway, California, 92064, United States

Location

Pacific Research Network, Inc.

San Diego, California, 92103, United States

Location

Research Alliance Inc.

Clearwater, Florida, 33756, United States

Location

The Neurology Research Group, LLC

Miami, Florida, 33186, United States

Location

Compass Research LLC

Orlando, Florida, 32806, United States

Location

IMIC, Inc.

Palmetto Bay, Florida, 33157, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

NeuroStudies.Net, LLC

Decatur, Georgia, 30033, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

PMG Research of Rocky Mount, LLC

Rocky Mount, North Carolina, 27804, United States

Location

The Clinical Trial Center

Jenkintown, Pennsylvania, 19046, United States

Location

Central Coast Neurosciences Research

Central Coast, New South Wales, 2261, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales, 2113, Australia

Location

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

Heidelberg West, Victoria, 3081, Australia

Location

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, 6009, Australia

Location

The Research Institute for the Care of Older People

Bath, Combe Park, BA1 3NG, United Kingdom

Location

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

Manchester, Lancashire, M8 5RB, United Kingdom

Location

West London Mental Health Trust

Isleworth, London, TW7 6FY, United Kingdom

Location

St Pancras Clinical Research

Kings Cross, London, WC1X 8QD, United Kingdom

Location

Institute of Clinical Sciences, Queen's University Belfast

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

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

Edinburgh, EH8 9YL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 28012176 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Cognitive Dysfunction

Interventions

UE2343

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Results Point of Contact

• Title: Director of Drug Development & Strategy
• Organization: Actinogen Medical Limited

info@actinogen.com.au

+61289647401

Study Officials

• Bill Ketelbey, MD

  Actinogen Medical

  STUDY CHAIR

• Alan Boyd, MD, FFPM

  Actinogen Medical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: April 5, 2016
• Study Start: March 23, 2017
• Primary Completion: March 15, 2019
• Study Completion: March 15, 2019
• Last Updated: February 3, 2025
• Results First Posted: May 6, 2021

Record last verified: 2022-04

Locations

AU (5); GB (6); US (14)