None listed
Conditions
Brief summary
This study aims to test whether ACE-2223-1 is safe and well tolerated when given as single or multiple oral doses to healthy adults, and to understand how the body absorbs and processes the drug at different dose levels. This is a Single and Multiple-Ascending Dose Study of ACE-2223-1 in Healthy Adult Participants. Who is it for? You may be eligible for this study if you are aged 18 to 65 years living and have a body mass index of greater than or equal to 18kg and less than or equal to 30kg without clinically significant (CS) medical history. Study details: Part A and Part B will consist of up to 6 cohorts of 8 healthy male or female adults, randomized 3:1 to receive ACE-2223-1 or placebo. Part B may be initiated after satisfactory review of safety and data from at least the first 3 cohorts in Part A.
Interventions
This is a Phase 1 first-in-human study of orally administered ACE-2223-1 consisting of single and multiple ascending dose parts in healthy adult participants.
Part A – Single Ascending Dose (SAD):
Participants will receive a single oral dose of ACE-2223-1 starting at 5 mg. Up to 6 ascending dose cohorts will be evaluated. Dose escalation will be determined by the Safety Review Committee (SRC) based on safety and pharmacokinetic data, with escalation steps not exceeding 3-fold. The maximum dose
This is a Phase 1 first-in-human study of orally administered ACE-2223-1 consisting of single and multiple ascending dose parts in healthy adult participants. Part A – Single Ascending Dose (SAD): Participants will receive a single oral dose of ACE-2223-1 starting at 5 mg. Up to 6 ascending dose cohorts will be evaluated. Dose escalation will be determined by the Safety Review Committee (SRC) based on safety and pharmacokinetic data, with escalation steps not exceeding 3-fold. The maximum dose is capped at a pre-specified exposure and the specific dose will be determined from pharmacokinetic data Part B – Multiple Ascending Dose (MAD): Participants will receive ACE-2223-1 for 7 consecutive days at a dose shown to be safe and well tolerated in Part A. Up to 6 ascending dose cohorts will be evaluated. Dosing will be once or twice daily as determined by the SRC based on safety and pharmacokinetic data. The maximum dose will not exceed the maximum dose tested in Part A. ACE-2223-1 will be administered orally as a liquid formulation in the fasted state. For twice-daily dosing, fasting requirements may be relaxed. All doses will be administered in a controlled clinical research unit (CRU) under direct supervision of study staff. Participants remain resident in the CRU during the dosing period and scheduled assessments, supporting adherence.
Sponsors
Acelot, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
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 who is 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, inclusive, 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 >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. A highly effective contraception method for a female participant in this study is one that has a failure rate of <1% when used consistently and correctly and includes one of the following: • Placement of an intrauterine device (IUD) or intrauterine system (IUS) including any hormone-eluting type. • Tubal ligation or ablation performed at least 6 months prior to screening. • Vasectomised partner (i.e., the female participant’s male partner has undergone effective surgical sterilisation [verbal history to confirm azoospermia at least 90 days after the procedure] before the female participant entered the clinical study and he is the sole sexual partner of the female participant during the clinical study). • Oral, injected, or implanted hormonal contraception is not considered a form of highly effective contraception for female participants in this study. Sole use of a condom, or use of a female diaphragm and male condom together, is not considered adequate contraception for this study. 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 as defined above, must agree to use adequate contraception (defined as use of a condom combined with a female partner using a highly effective method of contraception) from signing the ICF until at least 90 days after the last dose of study drug. c. Note: A highly effective contraception method for the female partner of a male participant is one that has a failure rate of less than 1% when used consistently and correctly and for this clinical study includes those listed above for female participants, as well as hormonal methods including hormone-eluting implants or injections, or the oral contraceptive pill. 7. Nonsmoker, or uses no more than 5 cigarettes or equivalent nicotine-containing products per week, and/or willing to abstain from smoking and the use of nicotine-containing products. 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. History of substance dependency (alcohol or other drugs of abuse), within 2 years prior to Day -1, or positive screen for drugs of abuse 10. Consumes excessive amounts of alcohol or unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU. 11. Unwilling to abstain from ingestion of caffeine or xanthine-containing products (e.g., caffeinated tea, coffee, chocolate, cola, etc.) 12. Consumption of grapefruit or Seville oranges 13. Unwilling to abstain from strenuous physical exercise (e.g., weight training, aerobics, etc.) beginning 72 hours prior to admission to the CRU and while in the CRU 14. 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 15. History of significant multiple and/or severe allergies, including anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food 16. 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 17. 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 18. Lactose intolerant or allergic to gluten or otherwise unable to consume standard meals provided in the CRU
Outcome results
None listed