None listed
Conditions
Brief summary
This study will evaluate the effect of a high-fat meal on the pharmacokinetics of a single oral dose of ACE-2223-1 in healthy adults. Participants will receive the solid formulation of ACE-2223-1 in a fasted state and after a standardized high-fat meal in a randomized, two-period crossover design. The study aims to determine how food intake alters the absorption, peak concentration, and overall exposure of ACE-2223-1. Up to 8 healthy male or female adults aged 18–65 years with a body mass index of 18–30 kg/m² will be enrolled. Safety, tolerability, and pharmacokinetics will be monitored throughout each intervention period.
Interventions
Part D (Food Effect, FE) will consist of an open-label, randomised sequence, 2-way crossover investigation to evaluate the effect of food on the pharmacokinetics of the ACE-2223-1 solid formulation. The dose level for this assessment will be determined based on emerging safety and pharmacokinetic data from Parts A and B but will not exceed two-thirds of the highest dose previously well tolerated. Participants will be admitted to the Clinical Research Unit (CRU) on Day -1 and remain there for 8 n
Part D (Food Effect, FE) will consist of an open-label, randomised sequence, 2-way crossover investigation to evaluate the effect of food on the pharmacokinetics of the ACE-2223-1 solid formulation. The dose level for this assessment will be determined based on emerging safety and pharmacokinetic data from Parts A and B but will not exceed two-thirds of the highest dose previously well tolerated. Participants will be admitted to the Clinical Research Unit (CRU) on Day -1 and remain there for 8 nights. The investigational product (IP) will be administered on two occasions (Day 1 and Day 5), once in the fasted state (no food or liquid except water for at least 10 hours prior to dosing) and once following a high-calorie, high-fat breakfast (containing approximately 800 to 1000 calories with 50% of the total calories derived from fat. The meal should derive approximately 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively). The two administrations will be separated by a washout period of at least 3 days or 5 half-lives of ACE-2223-1, whichever is longer (actual dosing days may be adjusted if required). All doses will be administered under direct supervision of study staff, and participants will remain resident in the CRU to ensure adherence. In this crossover design, the fed administration represents the intervention, and the fasted administration serves as the comparator.
Sponsors
Acelot, Inc.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects will be eligible for inclusion in the study if they meet all of the following criteria: 1. Adult male or female between 18 to 65 years old, inclusive. 2. Weight greater than 50 kg and less than or equal to 110 kg at Screening and at Day –1. 3. Body mass index (BMI) greater than or equal to 18 kg/m² and less than or equal to 30 kg/m² at Screening and at Day –1. 4. Judged to be in good health. 5. Female participants of child-bearing or non-childbearing potential are eligible: a. Non-childbearing potential is defined by either: * Surgically sterile (e.g., removal of both ovaries and/or uterus, or bilateral salpingectomy at least 6 months prior to first dosing), or * Naturally postmenopausal for at least 12 consecutive months prior to first dosing, with a FSH level greater than 40 mIU/mL at screening consistent with menopausal status. b. Female participants of child-bearing potential must: * Have a negative pregnancy test at the screening visit and on admission to the study site on Day -1. * Agree not to attempt to become pregnant from signing the informed consent form (ICF) until at least 30 days after the last dose of study drug. * Agree to use adequate contraception (condom by the male partner combined with a highly effective method of contraception) from one month prior to screening until at least 30 days after the last dose of study drug, if not exclusively in a same-sex relationship or true and consistent abstinence. * Agree not to donate eggs from signing the ICF until 30 days after the last dose of study drug. c. Highly effective contraception methods include: * Placement of an intrauterine device (IUD) or intrauterine system (IUS), including hormone-eluting. * Tubal ligation or ablation performed at least 6 months prior to screening. * Vasectomised partner (confirmed azoospermia at least 90 days after the procedure) who is the sole sexual partner during the study. * Note: Oral, injected, or implanted hormonal contraception alone is not considered highly effective for this study. Sole condom use or diaphragm plus condom is also not considered adequate. 6. Male participants must: a. Agree not to donate sperm from signing the ICF until at least 90 days after the last dose of study drug. b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (condom combined with female partner’s highly effective method) from signing the ICF until at least 90 days after the last dose. c. Note: Highly effective contraception for female partners includes those listed above, as well as hormonal methods (implants, injections, oral contraceptive pill). 7. Nonsmoker, or uses no more than 5 cigarettes or equivalent nicotine-containing products per week, or willing to abstain from smoking and nicotine-containing products during the study. 8. Willing and able to give informed consent and comply with protocol visit schedule, requirements, and restrictions.
Exclusion criteria
Participants who meet any of the following criteria will be excluded from participation in this trial: 1. History of cancer 2. Major surgery 3. Use of any prescription or over-the-counter medications, including herbals or routine vitamins or minerals, or other supplements, within 7 days or 5 half-lives (if known, whichever is longer) prior to Day-1.Oral contraceptives may be continued but cannot be relied on as highly effective and other methods of contraception must also be used. 4. If female, currently breastfeeding, lactating, or planning to breastfeed at any timepoint during the study 5. Prior cholecystectomy 6. Subjects with clinical laboratory evidence or clinical diagnosis of active viral hepatitis (HBV or HCV) or human immunodeficiency virus (HIV) infection; subjects with a positive SARS-CoV-2 test within 14 days prior to admission, or a symptomatic 7. Clinically significant abnormal screening ECG, including QTcF greater than 460ms (ECG may be repeated twice =10 minutes apart for an average value). 8. Family history of sudden death with unknown cause 9. Presence of epileptiform discharges in EEG at Screening 10. History of substance dependency (alcohol or other drugs of abuse), within 2 years prior to Day -1, orpositive screen for drugs of abuse 11. Consumes excessive amounts of alcohol or unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU. 12. Unwilling to abstain from ingestion of caffeine or xanthine-containing products (e.g., caffeinated tea, coffee, chocolate, cola, etc.) 13. Consumption of grapefruit or Seville oranges 15. Unwilling to abstain from strenuous physical exercise (e.g., weight training, aerobics, etc.) beginning72hours prior to admission to the CRU and while in the CRU 16. Use of any investigational product in any clinical trial within 30 days of admission or 5 half-lives, whichever is longer, or in the active follow-up phase of another clinical trial involving interventional treatment 17. History of significant multiple and/or severe allergies, including anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food 18. Clinically significant laboratory abnormalities at Screening or on Day -1, including a. AST, ALT, ALP, total bilirubin greater than 1.3 ULN; Participants with bilirubin elevations due to Gilbert’s syndrome may be eligible at the discretion of the PI b. eGFR less than 80 mL/min/1.73 m2 as calculated by the CKD-EPI equation Note: Abnormal laboratory results at Screening may be repeated once; other than the above tests, slight excursions outside the normal limits may be acceptable if viewed to be not clinically significant by the PI. 19. Vital signs outside the following ranges at Screening or Day -1: a. Systolic blood pressure 90 to 140 mm Hg, inclusive b. Diastolic blood pressure 40 to 90 mm Hg, inclusive c. Heart rate at rest 40 to 99 bpm, inclusive Vital signs may be repeated twice for an average value 20. Lactose intolerant or allergic to gluten or otherwise unable to consume standard meals provided in the CRU
Outcome results
None listed