Phase I MAD, Fed-Fasted, CSF Study of UE2343 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the drug UE2343, a potential treatment for Alzheimer's Disease (AD), is effective by assessing safety, tolerability, pharmacokinetics and pharmacodynamics in a Multiple Ascending Dose Study. Protocol amendments to the study will examine any food effect and determine if the drug penetrates the Blood-Brain Barrier.

Detailed Description
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Part 1 of this study is a double-blind, randomised, placebo-controlled, multiple ascending dose study to assess the safety, tolerability, PK and PD in healthy participants dosed twice daily at levels of 10, 20 and 35mg for 10 days.This part of the study will recruit 3 groups of 8 participants each. Part 2 is a cross-over study to assess the effects of food on the PK of UE2343 in healthy participants dosed with two single doses at a level decided from Part 1. This part of the study will recruit a total of 12 participants. Part 3 seeks to determine the PK of the UE2343 in CSF of healthy participants dosed twice daily for 4 days with a dose level determined from Part 1 and 2. This part of the study will recruit 4 participants. Strategies to ensure adherence to the study include the requirement that participants remain at the clinical research facility for the duration of their participation in the study; drug accountability checks (i.e. reconciliation of used and unused capsules) by an independent clinical research associate; and administration of the capsules to the participant by a member of the study site team.

Official Title
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A Phase I Double-Blind, Randomised, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of UE2343 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: UE2343
* Drug: Placebo
* Drug: Placebo
* Drug: UE2343
* Drug: UE2343


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to use specified contraception BMI within specified range No clinically significant abnormalities in the results of laboratory evaluations at Screening and Day -1. Exclusion Criteria: Abnormal medical history, including history of dementia No significant allergic reactions No prior drug or alcohol abuse Use of regular prescribed medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: MAD Study<br> | Drug: UE2343<br>* UE2343 10mg, 20, 35mg twice daily for 9 days<br>Drug: Placebo<br>* 10mg, 20, 35mg twice daily for 9 days<br>|
| Placebo Comparator: Fed-Fasted<br> | Drug: Placebo<br>* Cross-over study single dose administered twice (on day 1 and day 8) study duration 17 days<br>Drug: UE2343<br>* Cross-over study UE2343 single dose administered twice (on day 1 and day 8) study duration 17 days<br>|
| Experimental: CSF<br> | Drug: UE2343<br>* UE2343 twice daily for 3 days single dose on day 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Safety and Tolerability of UE2343 over 17 days including AEs, 12-lead ECGs, vital signs, Nerve conduction velocity, Labs. |  | Up to Day 17 | 
| Assess the Pharmacokinetic (PK) Plasma Parameter Maximum Plasma Concentration (Cmax) of UE2343 after a single dose |  | Day 1 and Day 8 | 
| Assess the Pharmacokinetic (PK) Plasma Parameter Time to Cmax (Tmax) of UE2343 after a single dose |  | Day 1 and Day 8 | 
| Assess the Pharmacokinetic (PK) Plasma Parameter Area Under the Curve (AUC) of UE2343 after a single dose |  | Day 1 and Day 8 | 
| Assess the Pharmacokinetic (PK) Plasma Parameter Terminal Elimination Half Life (t½) of UE2343 after a single dose |  | Day 1 and Day 8 | 
| Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF |  | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Pharmacokinetics (PK) Plasma parameter Maximum Plasma Concentration (Cmax) from time of dosing to 12 hours |  | Day 1 and Day 10 | 
| Assess Pharmacokinetics (PK) Plasma parameter Time to Cmax (Tmax) from time of dosing to 12 hours |  | Day 1 and Day 10 | 
| Assess Pharmacokinetics (PK) Plasma parameter Area Under the Curve (AUC) from time of dosing to 12 hours |  | Day 1 and Day 10 | 
| Assess Pharmacokinetics (PK) Plasma parameter Terminal Elimination Half Life (t½) from time of dosing to 12 hours |  | Day 1 and Day 10 | 
| Assess Pharmacokinetics (PK) Urine parameters (Amount of drug excreted in urine (Ae) and Ae as a % of dose) from time of dosing to 24 hours |  | Day 1 and Day 10 | 
| Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF compared to the Cmax value obtained in plasma |  | Day 4 | 
| Assess Pharmacodynamics (PD) Blood parameter Adrenocorticotropic hormone (ACTH) from baseline to end of study |  | Days 1, 10, 11, 12, 13 and 17. | 
| Assess Pharmacodynamics (PD) Blood parameter Serum Cortisol from baseline to end of study |  | Days 1, 10, 11, 12, 13 and 17. | 
| Assess Pharmacodynamics (PD) Blood parameter for Adrenal Androgens from baseline to end of study |  | Days 1, 10, 11, 12, 13 and 17. | 
| Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisol (UFF) from baseline to end of study |  | Days 1, 10, 11 and 12 | 
| Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisone (UFE) from baseline to end of study |  | Days 1, 10, 11 and 12 | 
| Assess Pharmacodynamics (PD) Urine parameter 5α-tetrahydrocortisol (5αTHF) from baseline to end of study |  | Days 1, 10, 11 and 12 | 
| Assess Pharmacodynamics (PD) Urine parameter 5β-tetrahydrocortisol (5βTHF) from baseline to end of study |  | Days 1, 10, 11 and 12 | 
| Assess Pharmacodynamics (PD) Urine parameter tetrahydrocortisone (THE) from baseline to end of study |  | Days 1, 10, 11 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xanamem