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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: UE2343; Drug: Placebo

• Registration Number: NCT02616445
• Lead Sponsor: Actinogen Medical

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-02
• Primary Completion: 2015-08
• Study Completion: 2015-09
• Study First Submitted: 2015-11-05
• Study First Submitted QC: 2015-11-25
• Study First Posted: 2015-11-30
• Status Verified: 2017-05
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
CSF	UE2343	-
Fed-Fasted	Placebo	-
MAD Study	Placebo	-
MAD Study	UE2343	-
Fed-Fasted	UE2343	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Assess Pharmacokinetics (PK) Plasma parameter Maximum Plasma Concentration (Cmax) from time of dosing to 12 hours	Day 1 and Day 10
Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisol (UFF) from baseline to end of study	Days 1, 10, 11 and 12
Assess Pharmacokinetics (PK) Plasma parameter Area Under the Curve (AUC) from time of dosing to 12 hours	Day 1 and Day 10
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 tetrahydrocortisone (THE) from baseline to end of study	Days 1, 10, 11 and 12
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 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 5β-tetrahydrocortisol (5βTHF) from baseline to end of study	Days 1, 10, 11 and 12
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 Terminal Elimination Half Life (t½) from time of dosing to 12 hours	Day 1 and Day 10
Assess Pharmacodynamics (PD) Blood parameter Adrenocorticotropic hormone (ACTH) from baseline to end of study	Days 1, 10, 11, 12, 13 and 17.

Trial Locations

Locations (1)

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia