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SafetyPhase 1XanaHESNCT03830762

Xanamem™ in Healthy Elderly Subjects

A Phase 1 study testing Xanamem in people with Safety and Peripheral Neuropathy, run by Actinogen Medical at 1 site in Australia.

Completed

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

Official record
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Trial summary

Xanamem™ is being developed as a potential drug for Alzheimer's disease. This study drug has been designed to change the cortisol levels in the brain. Cortisol is a naturally occurring hormone in the body. It is believed that reducing the level of cortisol will be a benefit in the treatment of Alzheimer's disease. Read more about this study

Who is it for?
Ages 50 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Safety, Peripheral Neuropathy, Cortisol
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
42 participants
Where
1 siteAustralia
Study dates
21 Jan 2019to 7 Jan 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Volunteers aged 50 to 75 years.
  • 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/mL, will be confirmed by the local laboratory.
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test.
  • 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
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  • Who are permanently sterile or have had bilateral orchiectomy or bilateral vasectomy.
  • No disease which may cause a peripheral neuropathy.
  • No evidence of alcohol abuse (defined as greater than 21 standard units per week for males and greater than 14 standard units per week for females).
  • Must provide written informed consent to participate in the study and be willing and able to participate for the maximum of 12 weeks of treatment and 16 weeks of site visits.

Who cannot join

  • Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
  • Body Mass Index (BMI) > 38 kg/m2
  • Clinically significant abnormal haematology, biochemistry and urine examination values, as determined by the investigator.
  • Participants who have a history of liver disease, including fatty liver, or LFT elevations requiring investigation will not be eligible.
  • Has had a significant systemic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator.
  • Documented diagnosis of Type I or Type II diabetes.
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  • Has a history of disease directly related to the hypothalamus, the pituitary and/or the adrenal glands which affects the hypothalamic-pituitary-adrenal axis function.
  • Has any uncontrolled clinical condition relating to glucose or lipid metabolism.
  • Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities. Clinical evidence of neuropathy.
  • Clinically significant electrocardiogram (ECG) abnormalities, including QTc interval > 450 msec (male) and > 470 msec (female), following ECG tracings at Screening.
  • Use of any prohibited medication.
  • Participation in another clinical study of a 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 questionnaires and study drug label will be provided in English only], poor mental development or impaired cerebral function).
  • Subject will undergo the Columbia Suicide Severity Rating Scale (CSSRS), Toronto Clinical Neuropathy Score (TCNS), EuroQoL Health Related Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L), and Cogstate Test Battery 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.
  • For subjects that consent, and are subsequently accepted for enrolled into, the CSF optional sub-study, subjects must have no contraindications to the lumbar puncture procedure as assessed by the Principal Investigator. Such contraindications may include uncontrolled bleeding abnormalities or skin or spine abnormalities.
  • Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). Subjects returning a positive result will be managed by the site in line with standard care.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Linear Clinical Research

    Perth, Western Australia, 6009

Other trials in Australia

About this study

Official title: XanaHES: A Phase I, Single Blinded, Central Reader Blinded, Placebo-Controlled, Dose Escalation Study of Xanamem™ to Assess Safety and Tolerability in Healthy Elderly Subjects

Xanamem™ is being developed as a potential drug for Alzheimer's disease. This study drug has been designed to change the cortisol levels in the brain. Cortisol is a naturally occurring hormone in the body. It is believed that reducing the level of cortisol will be a benefit in the treatment of Alzheimer's disease.

The XanaHES study is testing the safety and tolerability of Xanamem. It is planned to enrol approximately 84 participants, male and female aged from 50 to 75 who are in good health, in the study at 1 centre in Australia.

The XanaHES Phase I study is a single-blind study. Subjects will be randomised to receive either 20mg once daily Xanamem or Placebo in cohort 1. Once all subjects have completed the study treatment of 12 weeks, a dose escalation committee will decide if a new cohort, cohort 2, with 30mg once daily vs placebo is started.

Read the detailed description

This is a Phase I, randomised, single-centre, single-blind, placebo-controlled study to assess the safety, tolerability of oral Xanamem once daily in healthy elderly subjects.

It is planned to randomise approximately 84 subjects, 42 in each cohort, at a single site in Australia.

Cohort 1 starts with a 20mg QD dose vs matching placebo. A Dose Escalation Committee will review the results from cohort 1 and provide a recommendation to proceed with Cohort 2 randomisation which involves a dose escalation to 30mg.

At the Baseline visit (Week 0), eligible subjects will be randomised on a 30:12 ratio to receive either Xanamem administered orally QD (treatment group) or matching placebo (placebo group). Subjects will return to the study site for visits at Week 2, Week 4, Week 6, Week 8, Week 10, 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, routine safety evaluations and nerve function tests.

A central reader will review every Nerve Function Monitoring (NFM) assessment performed for each subject for Potential Nerve Safety Signals (PNSS).

Optional cerebrospinal fluid (CSF) sampling will be performed at baseline and end of treatment visits for a small subgroup of subjects, who provide additional consent. 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 up to 4 weeks, a single-blind treatment period of 12 weeks, and a follow-up period of 4 weeks. The total duration of the study is expected to be 1.5 years.

Being tested
Xanamem, Matching Placebo
Keywords
Actinogen, Xanamem, UE2343, Cortisol, 11β-HSD1, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Healthy Ageing, Peripheral Neuropathy, Safety, Dose Escalation, Elderly, XanaHES, emestedastat
Medical subject headings
Peripheral Nervous System Diseases, Small Fiber Neuropathy

What participants receive

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

  • XanamemDrug

    Also called UE2343

    Oral Xanamem capsules 20mg or 30mg, administered PO once daily. 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.

  • Matching PlaceboDrug

    Also called Placebo

    Matching placebo which is identical in appearance to the test product (20mg, 30mg Xanamem™ QD) except that it contains no active ingredient.

Study groups in NCT03830762
Study groupRoleWhat they receive
Cohort 1 / Cohort 2 (Active)Experimental20mg or 30mg capsules of Xanamem respectively, to be administered PO once daily.
Receives: Drug: Xanamem
Cohort 1 / Cohort 2 (Placebo)Placebo 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: Matching Placebo

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events (AEs)

    The number, type, and severity of treatment-emergent adverse events (AEs) that are reported from Screening Visit to Follow-up Visit will be collected and evaluated.

    Measured: 20 Weeks (Screening up to Week 16 Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  2. Incidence of Clinically Significant Changes in Serum Biomarker Levels in a Standard Serum Chemistry Panel

    Collection of blood samples for clinical laboratory testing to assess any clinically significant changes in standard serum chemistry measures.

    Measured: Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  3. Incidence of Clinically Significant Laboratory Haematological Biomarker Levels in a Standard Haematology Panel.

    Collection of blood samples for clinical laboratory testing to assess any clinically significant changes in standard haematology measures.

    Measured: Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  4. Incidence of Clinically Significant Changes or Abnormalities Following Physical Examination

    Evaluation of any clinically significant changes or abnormalities reported following a standard Physical Examination.

    Measured: Screening up to Week 16 (Follow-Up) and Unscheduled Safety Visit throughout duration of study up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  5. Nerve Conduction Assessments

    Nerve Conduction assessments will be used to detect presence and severity of nerve damage.

    Measured: Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  6. Neuropathy Total Symptom Score-6 (NTSS-6)

    Changes in the Neuropathy Total Symptom Score (NTSS-6) administered by a physician to assess a subjects' medical history. Each item will also be graded for its frequency and intensity, adding up to a total score from "0" to "21.96" points. A total score of > 6 would exclude the subject from the study.

    Measured: Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)

  7. Toronto Clinical Neuropathy Score (TCNS)

    Changes in Toronto Clinical Neuropathy Score (TCNS) to detect for neuropathy out of a total score of 19; scales are defined as follows: 0-5 = no neuropathy; 6-8 = mild neuropathy; 9-11 = moderate neuropathy; ≥ 12 = severe neuropathy.

    Measured: Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)

  8. Skin Biopsy

    A 3mm skin sample will be taken via skin punch biopsy to detect intra-epidermal nerve fiber density; this allows for the objectification and quantification of a small-fiber neuropathy.

    Measured: At Baseline and Week 12 (End of Treatment)

  9. Quantitative Sensory Testing (QST)

    Thermal sensory testing using Quantitative Sensory Testing (QST) for cold, warm and heat pain to detect peripheral nerve disorders.

    Measured: Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

  10. Columbia Suicide Severity Rating Scale (CSSRS)

    Any change in Columbia Suicide Severity Rating Scale (CSSRS) will assess suicidal ideation and behaviour.

    • Suicidal ideation score: Any score greater than 0 is important and may indicate the need for mental health intervention.
    • Suicidal ideation intensity rating: The five intensity item scores create a total score (range 0 to 25) to represent the intensity rating, if the patient did not endorse any suicidal ideation the intensity rating is 0.

    Measured: Screening, Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)

  11. Electrocardiogram (ECG)

    Any clinically significant electrocardiogram (ECG) abnormalities will be recorded, including corrected QT interval (QTc) of > 500 msec.

    Measured: Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

Timeline

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

  1. First posted5 Feb 2019
  2. Study start21 Jan 2019
  3. Primary completion7 Dec 2019
  4. Study completion7 Jan 2020

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 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
A Dose Escalation Committee will review the results from Cohort 1 (20 mg active vs. placebo arms) and provide a recommendation to proceed with Cohort 2 (30 mg active vs. placebo arms) randomisation which involves a dose escalation.
Masking
Single blind
Who is masked
Participant
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03830762
Sponsor's protocol ID
ACW0003
Acronym
XanaHES
Status last verified
Aug 2020
First submitted
23 Jan 2019
Last updated
22 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Xanamem in people with Safety and Peripheral Neuropathy, run by Actinogen Medical at 1 site in Australia.

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 10 inclusion and 16 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 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of Treatment-Emergent Adverse Events (AEs) (time frame: 20 Weeks (Screening up to Week 16 Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])). The study lists 11 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 NCT03830762, which also lists 1 linked publication.

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 22 Jan 2025.

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