A Double-Blind, Placebo-Controlled, Dose Ranging Study of Xanamem® in Healthy Elderly Volunteers (XanaMIA-DR)

XanaMIA-DR a Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy, Pharmacodynamics and Safety of Xanamem® in Healthy Elderly Volunteers

Xanamem® is being developed as a potential drug for Mild Cognitive Impairment in 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 Mild Cognitive Impairment in Alzheimer's disease.

The purpose of this study in older volunteers is to investigate the smallest dose of Xanamem® (5 mg or 10 mg) which works and to investigate which dose in this study will be used in the upcoming clinical trials in patients.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Alzheimer's Disease
• Intervention / Treatment: Drug: Xanamem® 5 mg; Drug: Xanamem® 10 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Bruce, Australian Capital Territory, Australia, 2617
      • Paratus Clinical Research Canberra
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Paratus Clinical Research Western Sydney
    • Kanwal, New South Wales, Australia, 2259
      • Paratus Clinical Research Central Coast
  • Queensland
    • Albion, Queensland, Australia, 4010
      • Paratus Clinical Research Brisbane
    • Sippy Downs, Queensland, Australia, 4556
      • USC Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female aged 50 to 80
2. Body mass index 17.5 to < 35 kg/m2, inclusive at the time of screening
3. Mini-Mental State Score of ≥ 25 points at screening
4. Must provide written informed consent

Exclusion Criteria:

1. Abnormalities in vital signs at screening or baseline
2. Clinically significant abnormal hematology or biochemistry values, as determined by the investigator at screening and/or baseline.
3. Previous clinically significant systemic illness or infection within the past 4 weeks prior to screening or baseline, as determined by the investigator
4. Clinically significant ECG abnormalities
5. Use of tobacco- or nicotine-containing products in the past month or unwillingness to abstain during study participation
6. Participation in another clinical study of a drug or device
7. Known allergy to the study drug (Xanamem®) or any of the excipients
8. Subjects who are likely to be unable to comply with the study schedule and/ or subjects with an inability to communicate well with the investigator
9. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies at screening
10. Subjects with a history of drug abuse or addiction in the past 5 years.
11. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xanamem® 5 mg; Oral Xanamem® capsules 5 mg, to be administered once daily	Drug: Xanamem® 5 mg; Oral Xanamem® ("UE2343") capsules 5 mg, administered orally once daily.
Experimental: Xanamem® 10 mg; Oral Xanamem® capsules 10 mg, to be administered once daily	Drug: Xanamem® 10 mg; Oral Xanamem® ("UE2343") capsules 10 mg, administered orally 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.	Drug: Placebo; Matching placebo which is identical in appearance to the test product (5 mg, 10 mg Xanamem® QD) except that it contains no active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term efficacy: Assessment of changes of different doses of Xanamem® on cognition.	Using a tailored Cogstate Neuropsychological Test Battery (NTB), changes from baseline, as well as composite scores based on a combination of these variables at each treatment visit [Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up)] will be analyzed.	Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up)
Assessment of safety and tolerability of different Xanamem® doses by the occurrence of Treatment-Emergent Adverse Events (TEAEs).	The number, type, and severity of Treatment-Emergent Adverse Events (TEAEs) that are reported from Baseline to Follow-up Visit will be collected and evaluated.	10 Weeks [Baseline to Week 10 Follow-Up (4 Weeks Post Last Dose of Study Drug)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term efficacy of different doses of Xanamem® on cognition	Using the International Daily Digit Symbol Substitution Test-Symbols, to analyze changes from Screening to, Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up).	Screening, Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up)

Collaborators and Investigators

• Sponsor: Actinogen Medical
• Collaborators: Avance Clinical Pty Ltd.
• Investigators: Study Director: Miriam Roesner, Actinogen Medical Limited

Publications and helpful links

General 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.

Helpful Links

• Selection and early clinical evaluation of the brain-penetrant 11β-HSD1 inhibitor UE2343

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): February 11, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: July 17, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Cognitive Function; emestedastat
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: ACW0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No