Tricaprilin Liquid Formulation PK Study
Phase 1
Terminated
- Conditions
- Alzheimer Disease
- Interventions
- Drug: AC-OLE-PDrug: AC-OLE-01Drug: AC-OLE-02Drug: AC-OLE-03Drug: AC-OLE-04Drug: AC-OLE-05Drug: AC-OLE-06Drug: AC-OLE-07Drug: AC-OLE-08Drug: AC-OLE-09Drug: AC-OLE-010
- Registration Number
- NCT05028114
- Lead Sponsor
- Cerecin
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 71
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 2 (Placebo Assessment) AC-OLE-P Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment. Participants are randomised to 1 of 2 sequences (tricaprilin formulation - matching placebo; matching placebo - tricaprilin formulation) with a 2-day washout between periods. Part 1 (Formulation Optimisation) AC-OLE-04 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-05 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-1202 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-06 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-010 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-01 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-02 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-03 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-08 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-09 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 1 (Formulation Optimisation) AC-OLE-07 Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration. Part 3 (Titration Tolerability) AC-OLE-P Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment. Participants will be randomised to either study drug or the matching placebo.
- Primary Outcome Measures
Name Time Method 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)
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)
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 Outcome Measures
Name Time Method 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.
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
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)
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)
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)
Trial Locations
- Locations (1)
CMAX
🇦🇺Adelaide, South Australia, Australia