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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02616445
• Other study ID #: ACW0001
• Status: Completed
• Phase: Phase 1
• First received: November 5, 2015
• Last updated: May 1, 2017
• Start date: February 2015
• Est. completion date: September 2015

Study information

• Verified date: May 2017
• Source: Actinogen Medical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• UE2343
UE2343 10mg, 20, 35mg twice daily for 9 days
• Placebo
10mg, 20, 35mg twice daily for 9 days
• Placebo
Cross-over study single dose administered twice (on day 1 and day 8) study duration 17 days
• UE2343
Cross-over study UE2343 single dose administered twice (on day 1 and day 8) study duration 17 days
• UE2343
UE2343 twice daily for 3 days single dose on day 4

Locations

Country	Name	City	State
Australia	Linear Clinical Research	Nedlands	Western Australia

Sponsors (3)

Lead Sponsor	Collaborator
Actinogen Medical	Linear Clinical Research, Novotech (Australia) Pty Limited

Country where clinical trial is conducted

Australia, 

References & Publications (1)

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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess Safety and Tolerability of UE2343 over 17 days including AEs, 12-lead ECGs, vital signs, Nerve conduction velocity, Labs.		Up to Day 17
Primary	Assess the Pharmacokinetic (PK) Plasma Parameter Maximum Plasma Concentration (Cmax) of UE2343 after a single dose		Day 1 and Day 8
Primary	Assess the Pharmacokinetic (PK) Plasma Parameter Time to Cmax (Tmax) of UE2343 after a single dose		Day 1 and Day 8
Primary	Assess the Pharmacokinetic (PK) Plasma Parameter Area Under the Curve (AUC) of UE2343 after a single dose		Day 1 and Day 8
Primary	Assess the Pharmacokinetic (PK) Plasma Parameter Terminal Elimination Half Life (t½) of UE2343 after a single dose		Day 1 and Day 8
Primary	Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF		Day 4
Secondary	Assess Pharmacokinetics (PK) Plasma parameter Maximum Plasma Concentration (Cmax) from time of dosing to 12 hours		Day 1 and Day 10
Secondary	Assess Pharmacokinetics (PK) Plasma parameter Time to Cmax (Tmax) from time of dosing to 12 hours		Day 1 and Day 10
Secondary	Assess Pharmacokinetics (PK) Plasma parameter Area Under the Curve (AUC) from time of dosing to 12 hours		Day 1 and Day 10
Secondary	Assess Pharmacokinetics (PK) Plasma parameter Terminal Elimination Half Life (t½) from time of dosing to 12 hours		Day 1 and Day 10
Secondary	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
Secondary	Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF compared to the Cmax value obtained in plasma		Day 4
Secondary	Assess Pharmacodynamics (PD) Blood parameter Adrenocorticotropic hormone (ACTH) from baseline to end of study		Days 1, 10, 11, 12, 13 and 17.
Secondary	Assess Pharmacodynamics (PD) Blood parameter Serum Cortisol from baseline to end of study		Days 1, 10, 11, 12, 13 and 17.
Secondary	Assess Pharmacodynamics (PD) Blood parameter for Adrenal Androgens from baseline to end of study		Days 1, 10, 11, 12, 13 and 17.
Secondary	Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisol (UFF) from baseline to end of study		Days 1, 10, 11 and 12
Secondary	Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisone (UFE) from baseline to end of study		Days 1, 10, 11 and 12
Secondary	Assess Pharmacodynamics (PD) Urine parameter 5a-tetrahydrocortisol (5aTHF) from baseline to end of study		Days 1, 10, 11 and 12
Secondary	Assess Pharmacodynamics (PD) Urine parameter 5ß-tetrahydrocortisol (5ßTHF) from baseline to end of study		Days 1, 10, 11 and 12
Secondary	Assess Pharmacodynamics (PD) Urine parameter tetrahydrocortisone (THE) from baseline to end of study		Days 1, 10, 11 and 12