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

Study Overview
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Brief Summary
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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.

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

Conditions
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Mild Cognitive Impairment, Alzheimer's Disease

Intervention / Treatment
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* Drug: Xanamem® 5 mg
* Drug: Placebo
* Drug: Xanamem® 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 50 to 80 Body mass index 17.5 to < 35 kg/m2, inclusive at the time of screening Mini-Mental State Score of ≥ 25 points at screening Must provide written informed consent Exclusion Criteria: Abnormalities in vital signs at screening or baseline Clinically significant abnormal hematology or biochemistry values, as determined by the investigator at screening and/or baseline. Previous clinically significant systemic illness or infection within the past 4 weeks prior to screening or baseline, as determined by the investigator Clinically significant ECG abnormalities Use of tobacco- or nicotine-containing products in the past month or unwillingness to abstain during study participation Participation in another clinical study of a drug or device Known allergy to the study drug (Xanamem®) or any of the excipients 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 Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies at screening Subjects with a history of drug abuse or addiction in the past 5 years. 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)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Volunteer subjects will be randomly assigned to 1 of 3 treatment groups to receive either 5 mg Xanamem®, 10 mg Xanamem® or placebo in the ratio of 1:1:1 with approximately 35 subjects in each treatment group. This sample size has been selected to allow for approximately 30 subjects per treatment group to complete the study.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive Function, Healthy Volunteers