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

Alzheimer Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03971123
• Other study ID #: AC-19-017
• Status: Completed
• Phase: Phase 1
• Start date: August 30, 2019
• Est. completion date: May 26, 2020

Study information

• Verified date: July 2020
• Source: Cerecin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 26, 2020
• Est. primary completion date: April 2, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

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
• Tricaprilin
Tricaprilin formulated as AC-LMP-01 50g of AC-LMP-01 (20g tricaprilin) mixed in 240mL dosing liquid at Hour 0 Day 1
• Placebo
Matching placebo to AC-SD-03 50g of AC-SD-03P mixed in 240mL dosing liquid at Hour 0 Day 1
• Tricaprilin
Tricaprilin formulated as AC-1202 60g of AC-1202 (20g caprlic triglyceride) mixed in 240mL dosing liquid at Hour 0 Day 1

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Cerecin

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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