Tricaprilin Liquid Formulation PK Study

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

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer Disease
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Formulation Optimisation); 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; Tricaprilin formulated as AC-1202; Drug: AC-OLE-01; Tricaprilin Formulation; Drug: AC-OLE-02; Tricaprilin Formulation; Drug: AC-OLE-03; Tricaprilin Formulation; Drug: AC-OLE-04; Tricaprilin Formulation; Drug: AC-OLE-05; Tricaprilin Formulation; Drug: AC-OLE-06; Tricaprilin Formulation; Drug: AC-OLE-07; Tricaprilin Formulation; Drug: AC-OLE-08; Tricaprilin Formulation; Drug: AC-OLE-09; Tricaprilin Formulation; Drug: AC-OLE-010; Tricaprilin Formulation
Experimental: Part 2 (Placebo Assessment); 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; Placebo to tricaprilin formulation
Experimental: Part 3 (Titration Tolerability); 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; Placebo to tricaprilin formulation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cerecin
• Investigators: Study Director: Study Director, Cerecin

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Actual): March 18, 2022
• Study Completion (Actual): July 19, 2022

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 15, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AC-21-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No