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

NCT03971123 | Completed Phase 1 FDA Drug

• 1 other identifier: AC-19-017
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• ApoE4 Genotyping (for Part 1 only)

  1 day

Study Arms (5)

AC-SD-03 (for Part 1)

EXPERIMENTAL

Tricaprilin SD formulation, single dose (20g tricaprilin). Administered orally.

Drug: Tricaprilin

AC-LMP-01 (for Part 1)

EXPERIMENTAL

Tricaprilin LMP formulation, single dose (20g tricaprilin). Administered orally.

Drug: Tricaprilin

AC-SD-03P (for Part 1)

EXPERIMENTAL

Placebo formulation, single dose. Administered orally

Drug: Placebo

AC-1202 (for Part 2)

EXPERIMENTAL

Tricaprilin SD formulation, single dose (20g caprylic triglyceride). Administered orally.

Drug: Tricaprilin

AC-SD-03 (for Part 2)

EXPERIMENTAL

Tricaprilin SD formulation, single dose (20g tricaprilin). Administered orally.

Drug: Tricaprilin

Interventions

Tricaprilin DRUG

Tricaprilin formulated as AC-SD-03 50g of AC-SD-03 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1

Also known as: AC-SD-03

AC-SD-03 (for Part 1); AC-SD-03 (for Part 2)

Placebo DRUG

Matching placebo to AC-SD-03 50g of AC-SD-03P mixed in 240mL dosing liquid at Hour 0 Day 1

Also known as: AC-SD-03P

AC-SD-03P (for Part 1)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cerecin: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

tricaprylin; AC-1202

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 3, 2019
• Study Start: August 30, 2019
• Primary Completion: April 2, 2020
• Study Completion: May 26, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)