Study to Compare the Pharmacokinetics of Tricaprilin Formulations and a Placebo on Ketone Body Production

A Phase 1, Randomised, Single-center, Single-dose, Placebo-controlled, 3-Way Crossover Study to Compare the Pharmacokinetics, Safety and Tolerability of a Lipid Multi-particulate (LMP) Formulation and Spray-dried (SD) Formulations of Tricaprilin (TC) on Ketone Body Production (Part 1). Addendum to Include a 2-way Crossover to Compare the Pharmacokinetics, Safety and Tolerability of Two Spray-dried (SD) Formulations of Tricaprilin (TC) on Ketone Body Production (Part 2)

Phase 1, Single-center, Open-label Study, Healthy Adult Male Subjects.

Part 1:Single-dose, Placebo-controlled, 3-Way Crossover PK Study

Part 2: Single dose 2-way comparator PK Study

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Tricaprilin; Drug: Tricaprilin; Drug: Tricaprilin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy, adult, male 18 - 50 years of age, inclusive, at Screening.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.
• Agrees to comply with study procedures.
• Continuous non smoker who has not used nicotine containing products or smoking no more than 10 cigarettes per week for at least 3 months prior to Screening and will not use them throughout the study.
• A non-vasectomized subject must agree to use a condom or abstain from sexual intercourse during the study. No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to Screening. A subject who has been vasectomized less than 4 months prior to Screening must follow the same restrictions as a non-vasectomized male.
• Subject is able and willing to consume a prescribed full breakfast on at least 3 occasions. Subject does not have specific dietary requirements (vegetarian, vegan, lactose-free, low-fat, etc.).
• Subject is not consuming a ketogenic diet (defined by consumption of < 50 gm carbohydrates per day).
• Has given voluntary, written informed consent to participate in the study.
• For Cohort 1, the Chinese subjects are restricted to being of Chinese heritage (irrespective of country of residence) and defined as all 4 grandparents of the subject must be Chinese (for Part 1 only).

Exclusion Criteria:

• History or presence of alcoholism or substance abuse disorder within the last year.
• Positive urine drug screen at Screening or Check-in.
• Subject is currently actively using MCTs, ketone esters, or other ketogenic products or is following a ketogenic diet.
• Clinically significant abnormal laboratory results at Screening.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing, administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Subject has a known allergy to the study drug's active or inactive ingredients.
• Subject has been following a ketogenic diet (or other diet incompatible with the on-study diet), in the opinion of the investigator.
• Unable to refrain from, or anticipates the use of, any drug including prescription and non-prescription medications, herbal remedies or vitamin supplements beginning 14 days prior to the first dose and throughout the study, unless deemed acceptable by the PI. Paracetamol (up to 4g per 24-hour period) or ibuprofen (up to 1,200 mg per 24-hour period) may be permitted during the study.
• Has had alcohol 48 hours prior to Day -1 of Period 1.
• Any other condition which, in the investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC-SD-03 (for Part 1); Tricaprilin SD formulation, single dose (20g tricaprilin). Administered orally.	Drug: Tricaprilin; Tricaprilin formulated as AC-SD-03 50g of AC-SD-03 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-SD-03; Drug: Tricaprilin; Tricaprilin formulated as AC-LMP-01 50g of AC-LMP-01 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-LMP-01; Drug: Tricaprilin; Tricaprilin formulated as AC-1202 60g of AC-1202 (20g caprlic triglyceride) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-1202
Experimental: AC-LMP-01 (for Part 1); Tricaprilin LMP formulation, single dose (20g tricaprilin). Administered orally.	Drug: Tricaprilin; Tricaprilin formulated as AC-SD-03 50g of AC-SD-03 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-SD-03; Drug: Tricaprilin; Tricaprilin formulated as AC-LMP-01 50g of AC-LMP-01 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-LMP-01; Drug: Tricaprilin; Tricaprilin formulated as AC-1202 60g of AC-1202 (20g caprlic triglyceride) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-1202
Experimental: AC-SD-03P (for Part 1); Placebo formulation, single dose. Administered orally	Drug: Placebo; Matching placebo to AC-SD-03 50g of AC-SD-03P mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-SD-03P
Experimental: AC-1202 (for Part 2); Tricaprilin SD formulation, single dose (20g caprylic triglyceride). Administered orally.	Drug: Tricaprilin; Tricaprilin formulated as AC-SD-03 50g of AC-SD-03 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-SD-03; Drug: Tricaprilin; Tricaprilin formulated as AC-LMP-01 50g of AC-LMP-01 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-LMP-01; Drug: Tricaprilin; Tricaprilin formulated as AC-1202 60g of AC-1202 (20g caprlic triglyceride) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-1202
Experimental: AC-SD-03 (for Part 2); Tricaprilin SD formulation, single dose (20g tricaprilin). Administered orally.	Drug: Tricaprilin; Tricaprilin formulated as AC-SD-03 50g of AC-SD-03 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-SD-03; Drug: Tricaprilin; Tricaprilin formulated as AC-LMP-01 50g of AC-LMP-01 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-LMP-01; Drug: Tricaprilin; Tricaprilin formulated as AC-1202 60g of AC-1202 (20g caprlic triglyceride) mixed in 240mL dosing liquid at Hour 0 Day 1; Other Names: AC-1202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of single-dose administration of each of tricaprilin formulations and the placebo formulation, in healthy, male volunteers (for Part 1 and 2)	Number of subjects with treatment related adverse events as assessed by CTCAE	11 days
Pharmacokinetics (PK) parameters of Total Ketones, Tricaprilin and Octanoic acid levels after single dose of each of tricaprilin formulations and the placebo formulation using AUC(0-t) (for Part 1 and 2)	AUC(0-t) will be calculated from PK concentrations of Total Ketones (B-hydroxybutyrate and Acetoacetate), Tricaprilin and Octanoic Acid Levels. AUC (0-t) = Area under the concentration-time curve from 0 to last quantifiable concentration. Summary statistics will be generated for each PK parameter.	1 day
Pharmacokinetics (PK) parameters of Total Ketones, Tricaprilin and Octanoic acid levels after single dose of each of tricaprilin formulations and the placebo formulation using Cmax (for Part 1 and 2)	Cmax will be calculated from PK concentrations of Total Ketones (B-hydroxybutyrate and Acetoacetate), Tricaprilin and Octanoic Acid Levels. Cmax = Cmax is maximum concentration, determined directly from individual concentration-time data.Summary statistics will be generated for each PK parameter.	1 day
Pharmacokinetics (PK) parameters of Total Ketones, Tricaprilin and Octanoic acid levels after single dose of each of tricaprilin formulations and the placebo formulation using Tmax (for Part 1 and 2)	Tmax will be calculated from PK concentrations of Total Ketones (B-hydroxybutyrate and Acetoacetate), Tricaprilin and Octanoic Acid Levels. Tmax = Time to reach maximum observed concentration, determined directly from individual concentration-time data.Summary statistics will be generated for each PK parameter.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ApoE4 Genotyping (for Part 1 only)	The Apo-E test provides a value represented by the type of the allele (E2, E3,E4).The allelic variant of the Apo-E (APOE4) will be evaluated for effects on tricaprilin induced ketone body production.	1 day

Collaborators and Investigators

• Sponsor: Cerecin

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2019
• Primary Completion (Actual): April 2, 2020
• Study Completion (Actual): May 26, 2020

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

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-19-017

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: Yes
• Studies a U.S. FDA-regulated device product: No