Tricaprilin Liquid Formulation PK Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics, safety, and tolerability of new liquid formulations of tricaprilin, with the aim of finding a suitable formulation to advance in development. This is a three-part, part-randomised study that include single-dose, food effect, and titration tolerability in up to 80 healthy participants.

Official Title
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A Phase 1, Three-part, Part-randomised, Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Different Formulations of Tricaprilin, to Include Single-dose, Food Effect, and Titration Tolerability, in Healthy Participants

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: AC-1202
* Drug: AC-OLE-01
* Drug: AC-OLE-02
* Drug: AC-OLE-03
* Drug: AC-OLE-04
* Drug: AC-OLE-05
* Drug: AC-OLE-06
* Drug: AC-OLE-07
* Drug: AC-OLE-08
* Drug: AC-OLE-09
* Drug: AC-OLE-010
* Drug: AC-OLE-P


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. Participants who are overtly healthy (in the opinion of the Investigator) as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring Body weight ≥45 kg and body mass index (BMI) within the range 18.0 - 32.0 kg/m2 (inclusive). Male and female Agrees to comply with study procedures including blood draws, confinement to clinic, meal requirements Continuous non-smoker or infrequent smoker (no more than 10 cigarettes per week for at least 3 months prior to Screening) Exclusion Criteria: History of, or current gastrointestinal (GI) conditions constituting a risk when taking the study treatment; or interfering with the interpretation of data, based on the Investigator's judgement Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen [up to 2 g per day], hormone replacement therapy and hormonal contraception are permitted). Participants on a ketogenic diet, low-fat diet or actively using medium chain triglycerides, ketone esters, or other ketogenic products.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 three-part study. Part 1 (Formulation Optimisation): Participants will be assigned to all 4 different formulations of tricaprilin, with randomization to one of 4 sequences with a 2-day washout in between different formulations. There are 2 series in this part. Part 1 (Food Effect): Participants will be administered to 1 formulation of tricaprilin. There are 2 series in this part. Part 2 (Placebo Assessment): Participants will be randomised to 1 of 2 sequences (tricaprilin formulation - matching placebo; matching placebo - tricaprilin formulation) with a 2-day washout between periods. Part 3 (Titration Tolerability): Participants will be administered to either tricaprilin or a matching placebo.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Formulation Optimisation)<br>Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. | Drug: AC-1202<br>* Tricaprilin formulated as AC-1202<br>Drug: AC-OLE-01<br>* Tricaprilin Formulation<br>Drug: AC-OLE-02<br>* Tricaprilin Formulation<br>Drug: AC-OLE-03<br>* Tricaprilin Formulation<br>Drug: AC-OLE-04<br>* Tricaprilin Formulation<br>Drug: AC-OLE-05<br>* Tricaprilin Formulation<br>Drug: AC-OLE-06<br>* Tricaprilin Formulation<br>Drug: AC-OLE-07<br>* Tricaprilin Formulation<br>Drug: AC-OLE-08<br>* Tricaprilin Formulation<br>Drug: AC-OLE-09<br>* Tricaprilin Formulation<br>Drug: AC-OLE-010<br>* Tricaprilin Formulation<br>|
| Experimental: Part 2 (Placebo Assessment)<br>Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment. Participants are randomised to 1 of 2 sequences (tricaprilin formulation - matching placebo; matching placebo - tricaprilin formulation) with a 2-day washout between periods. | Drug: AC-OLE-P<br>* Placebo to tricaprilin formulation<br>|
| Experimental: Part 3 (Titration Tolerability)<br>Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment. Participants will be randomised to either study drug or the matching placebo. | Drug: AC-OLE-P<br>* Placebo to tricaprilin formulation<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 1, Part 2) | 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 single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2) | Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | 0 to 8 hours post-dose | 
| Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2) | Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | 0 to 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | Adverse event incidence will be tabulated | Baseline to end of treatment period | 
| Gastrointestinal side effects of single-dose administration of each of tricaprilin formulations and the placebo formulation (Parts 1, 2) assessed using the Baxter Retching Faces Scale | The Baxter Retching Faces Scale is a pictorial scale rated from 0 to 10, with 6 faces depicting level of nausea/gastrointestinal discomfort. | Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose | 
| Gastrointestinal side effects of single-dose administration of each of tricaprilin formulations and the placebo formulation (Parts 1, 2) assessed using the Pain Numerical Rating Scale | The Pain Numerical Rating Scale 10-point numeric rating scale with participants instructed to rate any abdominal pain from 0 (no pain) to 10 (worst possible pain) | Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose | 
| Area under the concentration-time curve (AUC) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3) | AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose | 
| Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3) | Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose | 
| Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3) | Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose |