Tricaprilin Liquid Formulation PK Study

NCT05028114 | Terminated Phase 1

• 1 other identifier: AC-21-025
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Incidence of treatment emergent adverse events

  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

  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

  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)

  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)

  Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose

Study Arms (3)

Part 1 (Formulation Optimisation)

EXPERIMENTAL

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; 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

Part 2 (Placebo Assessment)

EXPERIMENTAL

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

Part 3 (Titration Tolerability)

EXPERIMENTAL

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

Interventions

AC-1202 DRUG

Tricaprilin formulated as AC-1202

Part 1 (Formulation Optimisation)

AC-OLE-01 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-02 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-03 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-04 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-05 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-06 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-07 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-08 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-09 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-010 DRUG

Tricaprilin Formulation

Part 1 (Formulation Optimisation)

AC-OLE-P DRUG

Placebo to tricaprilin formulation

Part 2 (Placebo Assessment); Part 3 (Titration Tolerability)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cerecin: lead

Study Sites (1)

CMAX

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

AC-1202

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Study Director

  Cerecin

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 31, 2021
• Study Start: August 31, 2021
• Primary Completion: March 18, 2022
• Study Completion: July 19, 2022
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)