Alzheimer Disease
Conditions
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.
Interventions
DRUGAC-1202
Tricaprilin formulated as AC-1202
DRUGAC-OLE-01
Tricaprilin Formulation
DRUGAC-OLE-02
Tricaprilin Formulation
DRUGAC-OLE-03
Tricaprilin Formulation
DRUGAC-OLE-04
Tricaprilin Formulation
DRUGAC-OLE-05
Tricaprilin Formulation
DRUGAC-OLE-06
Tricaprilin Formulation
DRUGAC-OLE-07
Tricaprilin Formulation
DRUGAC-OLE-08
Tricaprilin Formulation
DRUGAC-OLE-09
Tricaprilin Formulation
DRUGAC-OLE-010
Tricaprilin Formulation
DRUGAC-OLE-P
Placebo to tricaprilin formulation
Sponsors
Cerecin
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 0 to 8 hours post-dose | 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) | 0 to 8 hours post-dose | 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) | 0 to 8 hours post-dose | Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose | AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) |
| Incidence of treatment emergent adverse events | Baseline to end of treatment period | Adverse event incidence will be tabulated |
| Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose | Tmax 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) | Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose | Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate) |
| 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 | Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose | 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 | Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose | 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) |
Countries
Australia
Outcome results
None listed