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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: UE2343; Drug: Placebo; Drug: Placebo; Drug: UE2343; Drug: UE2343

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Actinogen Medical
• Collaborators: Novotech (Australia) Pty Limited; Linear Clinical Research
• Investigators: Study Chair: Vincent Ruffles, Actinogen Medical; Principal Investigator: Janakan Krishnarajah, Linear Clinical Research 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimated): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Xanamem; emestedastat
• Other Study ID Numbers: ACW0001

Plan for Individual participant data (IPD)

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