Clinical trial NCT02616445: Phase I MAD, Fed-Fasted, CSF Study of UE2343 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Xanamem
emestedastat
Lead sponsor: Actinogen Medical
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
name: Linear Clinical Research
First posted: 2015-11-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Assess Safety and Tolerability of UE2343 over 17 days including AEs, 12-lead ECGs, vital signs, Nerve conduction velocity, Labs.
timeFrame: Up to Day 17
measure: Assess the Pharmacokinetic (PK) Plasma Parameter Maximum Plasma Concentration (Cmax) of UE2343 after a single dose
timeFrame: Day 1 and Day 8
measure: Assess the Pharmacokinetic (PK) Plasma Parameter Time to Cmax (Tmax) of UE2343 after a single dose
timeFrame: Day 1 and Day 8
measure: Assess the Pharmacokinetic (PK) Plasma Parameter Area Under the Curve (AUC) of UE2343 after a single dose
timeFrame: Day 1 and Day 8
measure: Assess the Pharmacokinetic (PK) Plasma Parameter Terminal Elimination Half Life (t½) of UE2343 after a single dose
timeFrame: Day 1 and Day 8
measure: Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF
timeFrame: Day 4
Secondary outcomes:
measure: Assess Pharmacokinetics (PK) Plasma parameter Maximum Plasma Concentration (Cmax) from time of dosing to 12 hours
timeFrame: Day 1 and Day 10
measure: Assess Pharmacokinetics (PK) Plasma parameter Time to Cmax (Tmax) from time of dosing to 12 hours
timeFrame: Day 1 and Day 10
measure: Assess Pharmacokinetics (PK) Plasma parameter Area Under the Curve (AUC) from time of dosing to 12 hours
timeFrame: Day 1 and Day 10
measure: Assess Pharmacokinetics (PK) Plasma parameter Terminal Elimination Half Life (t½) from time of dosing to 12 hours
timeFrame: Day 1 and Day 10
measure: 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
timeFrame: Day 1 and Day 10
measure: Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF compared to the Cmax value obtained in plasma
timeFrame: Day 4
measure: Assess Pharmacodynamics (PD) Blood parameter Adrenocorticotropic hormone (ACTH) from baseline to end of study
timeFrame: Days 1, 10, 11, 12, 13 and 17.
measure: Assess Pharmacodynamics (PD) Blood parameter Serum Cortisol from baseline to end of study
timeFrame: Days 1, 10, 11, 12, 13 and 17.
measure: Assess Pharmacodynamics (PD) Blood parameter for Adrenal Androgens from baseline to end of study
timeFrame: Days 1, 10, 11, 12, 13 and 17.
measure: Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisol (UFF) from baseline to end of study
timeFrame: Days 1, 10, 11 and 12
measure: Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisone (UFE) from baseline to end of study
timeFrame: Days 1, 10, 11 and 12
measure: Assess Pharmacodynamics (PD) Urine parameter 5α-tetrahydrocortisol (5αTHF) from baseline to end of study
timeFrame: Days 1, 10, 11 and 12
measure: Assess Pharmacodynamics (PD) Urine parameter 5β-tetrahydrocortisol (5βTHF) from baseline to end of study
timeFrame: Days 1, 10, 11 and 12
measure: Assess Pharmacodynamics (PD) Urine parameter tetrahydrocortisone (THE) from baseline to end of study
timeFrame: Days 1, 10, 11 and 12
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: Actinogen Medical
name: Vincent Ruffles
role: STUDY_CHAIR
affiliation: Linear Clinical Research Limited
name: Janakan Krishnarajah
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.