Clinical trial NCT05028114: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Cerecin
Sponsor class: INDUSTRY
First posted: 2021-08-31
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: 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)
timeFrame: 0 to 8 hours post-dose
measure: Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)
timeFrame: 0 to 8 hours post-dose
measure: 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)
timeFrame: 0 to 8 hours post-dose
Secondary outcomes:
measure: Incidence of treatment emergent adverse events
timeFrame: Baseline to end of treatment period
measure: 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
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose
measure: 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
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose
measure: 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)
timeFrame: Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose
measure: Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)
timeFrame: Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose
measure: Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)
timeFrame: Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
Study officials:
affiliation: Cerecin
name: Study Director
role: STUDY_DIRECTOR
References: