Phase I MAD, Fed-Fasted, CSF Study of UE2343 in Healthy Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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
|
| Placebo Comparator: Fed-Fasted
|
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
|
| Experimental: CSF
|
Drug: UE2343
UE2343
twice daily for 3 days
single dose on day 4
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Linear Clinical Research | Nedlands | Western Australia | Australia | 6009 |
Sponsors and Collaborators
- Actinogen Medical
- Novotech (Australia) Pty Limited
- Linear Clinical Research
Investigators
- Study Chair: Vincent Ruffles, Actinogen Medical
- Principal Investigator: Janakan Krishnarajah, Linear Clinical Research Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACW0001