A Phase 1, Two-part, Randomized Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Liquid Formulation of Tricaprilin and Matching Placebo in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the PK, safety, and tolerability of a new liquid formulation of tricaprilin.

Official Title
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A Phase 1, Two-part, Randomized Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Liquid Formulation of Tricaprilin, and Matching Placebo to Include Single-dose and Food Effect (Part A), and Titration Tolerability (Part B), in Healthy Subjects

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: AC-OLE-01-VA


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Healthy males and non-pregnant, non-lactating healthy females aged 18 to 55 years inclusive at time of signing informed consent with a body weight ≥55 kg. Body mass index (BMI) 18.0 to 32.0 kg/m2 as measured at screening or, if outside the range, considered not clinically significant by the investigator. Main Exclusion Criteria: Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients Subjects with a history of fainting, dizziness, bradycardia or hypotension as considered clinically significant by the investigator Subject has a medical condition that may adversely affect taste or smell activity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a two-part study. Part A (Food Effect Assessment): It is a randomized, double-blind (to IMP received), placebo-controlled, four-period, single-dose design. Subjects will be dosed in the fed state or the fasted state depending on the regimen. Part B (Titration Tolerability): Participants will be administered to either tricaprilin or a matching placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Food Effect Assessment<br>Subjects will be randomized before administration of the first dose of active or matching placebo IMP in a 1:1:1:1 ratio to 1 of 4 treatment sequences (ABCD, BACD, ABDC, BADC) so that all subjects receive Regimens A, B, C and D across the 4 periods. | Drug: AC-OLE-01-VA<br>* formulation of tricaprilin or matching placebo<br>|
| Experimental: Part B - Titration Tolerability<br>Subjects will be dosed BID in the morning and afternoon (approximately 5 h apart) on Days 1 to 27. Both doses of active or matching placebo IMP will be administered in the fed state either 30 min after completion of a standard-fat and calorie content breakfast or 30 min after a standardized-fat and calorie content lunch. Participants will be randomised to either study drug or the matching placebo. | Drug: AC-OLE-01-VA<br>* formulation of tricaprilin or matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part A) | AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | 0 to 8 hours post-dose | 
| Incidence of Treatment Emergent Adverse Events (Part B) | Adverse event incidence will be tabulated | Baseline to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (Part A) | Adverse event incidence will be tabulated [BARF] Scale) | Baseline to 8 days | 
| Area under the concentration-time curve (AUC) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part B) | AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | 0 to 8 hours post-dose | 
| Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) after administration of tricaprilin and placebo formulations (Part A, Part B) | Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | 0 to 8 hours post-dose |