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Tricaprilin Liquid Formulation PK Study

Primary Purpose

Alzheimer Disease

Status

Terminated

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

AC-1202

AC-OLE-01

AC-OLE-02

AC-OLE-03

AC-OLE-04

AC-OLE-05

AC-OLE-06

AC-OLE-07

AC-OLE-08

AC-OLE-09

AC-OLE-010

AC-OLE-P

About this trial

This is an interventional basic science trial for Alzheimer Disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

CMAX

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part 1 (Formulation Optimisation)

Part 2 (Placebo Assessment)

Part 3 (Titration Tolerability)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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)

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)

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)

Secondary Outcome Measures

Incidence of treatment emergent adverse events

Adverse event incidence will be tabulated

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.

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)

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)

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)

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)

Full Information

NCT ID

NCT05028114

First Posted

August 19, 2021

Last Updated

October 15, 2023

Sponsor

Cerecin

1. Study Identification

Unique Protocol Identification Number

NCT05028114

Brief Title

Tricaprilin Liquid Formulation PK Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Terminated

Why Stopped

Part 1 was completed, Part 2 and Part 3 of the study were not conducted under this study protocol due to subject recruitment difficulty.

Study Start Date

August 31, 2021 (Actual)

Primary Completion Date

March 18, 2022 (Actual)

Study Completion Date

July 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cerecin

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

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)

Allocation

Randomized

Enrollment

71 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 (Formulation Optimisation)

Arm Type

Experimental

Arm Description

Arm Title

Part 2 (Placebo Assessment)

Arm Type

Experimental

Arm Description

Arm Title

Part 3 (Titration Tolerability)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

AC-1202

Intervention Description

Tricaprilin formulated as AC-1202

Intervention Type

Drug

Intervention Name(s)

AC-OLE-01

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-02

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-03

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-04

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-05

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-06

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-07

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-08

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-09

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-010

Intervention Description

Tricaprilin Formulation

Intervention Type

Drug

Intervention Name(s)

AC-OLE-P

Intervention Description

Placebo to tricaprilin formulation

Primary Outcome Measure Information:

Title

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)

Description

AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

0 to 8 hours post-dose

Title

Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)

Description

Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

0 to 8 hours post-dose

Title

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)

Description

Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

0 to 8 hours post-dose

Secondary Outcome Measure Information:

Title

Incidence of treatment emergent adverse events

Description

Adverse event incidence will be tabulated

Time Frame

Baseline to end of treatment period

Title

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

Description

The Baxter Retching Faces Scale is a pictorial scale rated from 0 to 10, with 6 faces depicting level of nausea/gastrointestinal discomfort.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose

Title

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

Description

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)

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose

Title

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)

Description

AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

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

Title

Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)

Description

Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

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

Title

Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)

Description

Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Cerecin

Official's Role

Study Director

Facility Information:

Facility Name

CMAX

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

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Tricaprilin Liquid Formulation PK Study

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