Cognitive Impairment, Major Depressive Disorder, MDD
Conditions
Keywords
Xanamem, UE2343, Actinogen, Cortisol, 11β-HSD1, 11-beta-Hydroxysteroid Dehydrogenase Type 1, emestedastat
Brief summary
Xanamem is being developed as a potential treatment for symptomatic, early stages of Alzheimer's Disease (AD) and Major Depressive Disorder (MDD). This XanaCIDD Phase II study in MDD is to investigate the safety and efficacy of Xanamem™ in treating patients with cognitive and depressive symptoms. Trial participants will be randomized to either receive 10mg of Xanamem™ once daily or a Placebo at a 1:1 ratio in a double-blinded fashion.
Interventions
DRUGXanamem™
Xanamem™ is formulated in green and cream-colored size 3, Coni-Snap-shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains the active pharmaceutical ingredient of UE2343.
DRUGPlacebo
Matching placebo which is identical in appearance to the test product (10 mg Xanamem™ QD) except that it contains no active ingredient.
Sponsors
AXIOM Real Time Metrics
Actinogen Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
placebo-controlled, parallel-group, double-blind, proof-of-concept trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female aged 18 to 75, inclusive. * Positive MDD primary diagnosis confirmed by the Mini-International Neuropsychiatric Interview (MINI). * Persistent depressive symptoms as determined by a Hamilton Depression Rating Scale (HAM-D) ≥ 17 at Screening. * Cognitive abilities on a coding test \> 0.5 standard deviations below expected. * Self-reported subjective cognitive dysfunction. * Currently or previously treated with a stable dose of a first- or second-line antidepressant that is approved for the treatment of depression (but not a tricyclic antidepressant, monoamine oxidase inhibitor, or vortioxetine). If on current treatment, dose must be stable for at least 6 weeks. * Smokers are eligible if they are able to comfortably abstain from nicotine for 2 hours prior to scheduled cognitive assessments. * Able to comfortably abstain from caffeine intake for 4 hours prior to scheduled cognitive assessments. * Must provide written informed consent to participate in the trial and be willing and able to comply with the requirements of the protocol and complete all trial visits. Key
Exclusion criteria
* Active suicidal ideation within the previous 3 months * On a tricyclic antidepressant, monoamine oxidase inhibitor, esketamine, or vortioxetine. * A history of clinically diagnosed dementia of any type * Previous clinically significant systemic illness or infection, including test positive COVID-19, within the past 4 weeks prior to Screening * Has a BMI or body weight that will interfere with participation in the trial * Type I or Type II diabetes requiring insulin * Clinically significant ECG abnormalities * Participation in another clinical trial of a drug or device * Trial participants who in the opinion of the Investigator exhibit physical, cognitive, or language impairments of such severity as to adversely affect the validity of the data derived from the neuropsychological tests. * Positive testing for HIV, hepatitis B surface antigen, or hepatitis C antibodies at Screening. * Participants with a history of drug abuse or addiction in the past 2 years * Current use of cannabis/marijuana, or tetrahydrocannabinol-containing medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Xanamem on attention, including working memory | 6 Weeks (Baseline to Week 6 (end of treatment (EOT))) | Change from Baseline to EOT in an Attention Composite of a Cognitive Test Battery (CTB) (Detection, Identification, and One Back tests) |
| Evaluation of the short-term safety and tolerability of Xanamem | 6 Weeks (Baseline to Week 6 (EOT)) | Incidence and severity of treatment-emergent adverse events (TEAEs) Incidence of serious adverse events (SAEs) and SUSARs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the effects of Xanamem on depressive symptoms | 6 Weeks (Baseline to Week 6 (EOT)) | Change from Baseline to EOT on the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a 10-item diagnostic questionnaire used to assess the severity of depressive episodes and is designed to be sensitive to treatment effects. Each item is scored from 0 to 6, and overall scores range from 0 to 60. Higher scores indicate greater severity. |
Countries
Australia, United Kingdom
Outcome results
None listed