None listed
Conditions
Brief summary
This is a single ascending dose study of ACE-2223-1 in healthy adult participants. You may be eligible for this study if you are aged 18 to 65 years and have a body mass index greater than or equal to 18 kg/m² and less than or equal to 30 kg/m², without any clinically significant medical history. Part C will determine the relative bioavailability (RBA) of an ACE-2223-1 solid formulation compared with the liquid formulation used in Parts A and B. Participants will receive both formulations in a randomized sequence with a washout period between doses. This part of the study aims to determine whether the new solid formulation of ACE-2223-1 is absorbed into the body in a similar way to the liquid formulation. We expect that the solid formulation will have comparable levels in the blood as the liquid, indicating it can be used interchangeably.
Interventions
Part C will consist of an open-label, randomised sequence, 2-way crossover investigation to compare the relative bioavailability (RBA) of a single ACE-2223-1 dose using two different formulations: one liquid formulation and one solid formulation. Part C may start prior to the completion of Part A and/or Part B. The dose level to be used for the assessment of the RBA will be determined based on emerging data from Part A and/or Part B.
The starting dose for Part C will not be lower than the starti
Part C will consist of an open-label, randomised sequence, 2-way crossover investigation to compare the relative bioavailability (RBA) of a single ACE-2223-1 dose using two different formulations: one liquid formulation and one solid formulation. Part C may start prior to the completion of Part A and/or Part B. The dose level to be used for the assessment of the RBA will be determined based on emerging data from Part A and/or Part B. The starting dose for Part C will not be lower than the starting dose evaluated in Part A (5 mg). The maximum dose will not exceed the highest dose shown to be safe and well tolerated in Parts A and/or B. Participants will be admitted to the Clinical Research Unit (CRU) on Day -1 and remain resident for 8 nights. Investigational product (IP) will be administered on 2 occasions (Day 1 and Day 5), once as a liquid formulation and once as a solid formulation, separated by a washout period of at least 3 days or 5 half-lives, whichever is longer (actual dosing days may be adjusted). The starting dose will be the same as the dose shown to be safe and well tolerated in Part A and/or Part B. Exact doses for the RBA assessment will be confirmed based on safety and pharmacokinetic data from Parts A and B. Mode of administration: Liquid formulation: Administered orally as a measured liquid; the liquid will be mixed with water (volume per protocol, typically 50–100 mL) and consumed under direct supervision. Solid formulation: Administered orally with water, under direct supervision. All doses will be administered under direct observation by CRU staff, ensuring full compliance with study drug administration. Participants remain resident in the CRU during dosing and scheduled assessments.
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 for inclusion: 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 (spontaneous cessation of menses) 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 ICF until at least 30 days after the last dose of study drug. • Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception as described below) 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, when this is the participant’s preferred and usual lifestyle as evaluated by the Investigator. • Must agree not to donate eggs from signing the ICF until 30 days after the last dose of study drug. c. Highly effective contraception methods for female participants (failure rate of less than 1% when used consistently and correctly) include: • Placement of an intrauterine device (IUD) or intrauterine system (IUS), including hormone-eluting devices. • Tubal ligation or ablation performed at least 6 months prior to screening. • Vasectomised partner (male partner has undergone effective surgical sterilisation, confirmed by verbal history of azoospermia at least 90 days prior, and is the sole sexual partner of the female participant). • Oral, injected, or implanted hormonal contraception is **not** considered highly effective for this study. • Sole use of a condom, or use of a female diaphragm and male condom together, is not considered adequate contraception. 6. Male volunteers: a. Must 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, must agree to use adequate contraception (condom combined with female partner using a highly effective method) from signing the ICF until at least 90 days after the last dose. c. Highly effective contraception methods for female partners of male participants include those listed above, as well as hormonal methods (oral contraceptive pill, hormone-eluting implants or injections). 7. Nonsmoker, or uses no more than 5 cigarettes or equivalent nicotine-containing products per week, and/or willing to abstain from smoking and use of nicotine-containing products during the study. 8. Willing and able to give informed consent and comply with the 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, or positive 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.) beginning 72hours 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