None listed
Conditions
Brief summary
Part C - In a randomized, open-label, two-period crossover design, at least 12 healthy participants will be randomly assigned to the FP (fasting-postprandial) group and PF (postprandial-fasting) group in a 1:1 ratio. All participants will take ACT004 capsules. The FP group will be given ACT004 capsules in the first period under fasting condition and in the second period under postprandial condition; the PF group will be given ACT004 capsules in the first period under postprandial condition and in the second period under fasting condition, with two periods of cross-administration and a wash-out period of 5 days. The planned dose regimen for Part C may be adjusted by the SRC according to safety, tolerability, and PK and results of Part A. Participants will be screened within 28 days prior to dosing and admitted to the clinical site on Day -1. Eligible participants will receive ACT004 on Day 1 and Day 6 under fasting or postprandial conditions in the group that they were randomized to. Following completion of all PK sample collection and safety assessments, participants will be discharged on Day 7 and followed up on Day 10 (±1 day).
Interventions
Part C- Food Effect (FE) (Cohort C1) Approximately 38 days - The planned dose regimen for Part C may be adjusted by the SRC according to safety, tolerability, and PK results of Part A. Healthy volunteers will be screened to achieve at least 12 evaluable subjects; in the event of early withdrawals, subjects may be replaced. In a randomized, open-label, two-period crossover design, at least 12 evaluable subjects will be randomly assigned to the FP (fasting-postprandial) group and PF (postprandial-
Part C- Food Effect (FE) (Cohort C1) Approximately 38 days - The planned dose regimen for Part C may be adjusted by the SRC according to safety, tolerability, and PK results of Part A. Healthy volunteers will be screened to achieve at least 12 evaluable subjects; in the event of early withdrawals, subjects may be replaced. In a randomized, open-label, two-period crossover design, at least 12 evaluable subjects will be randomly assigned to the FP (fasting-postprandial) group and PF (postprandial-fasting) group in a 1:1 ratio. All subjects will take ACT004 capsules orally. The FP group will be given ACT004 capsules in the first period under fasting condition and in the second period under postprandial condition; the PF group will be given ACT004 capsules in the first period under postprandial condition and in the second period under fasting condition, with two periods of cross-administration and a wash-out period of 5 days. Healthy subjects will be screened within 28 days prior to dosing and admitted to the clinical site on Day -1. Eligible subjects will receive ACT004 on Day 1 and Day 6 under fasting or postprandial conditions in the group that they were randomized to. Following completion of all PK sample collection and safety assessments, subjects will be discharged on Day 7 and return to the clinic on Day 10 (End of Study/Early Termination Visit). Telemetry monitoring will be performed continuously from pre-dose to 6 hour post dose in Part C participants. Telemetry monitoring includes blood pressure, heart rate, and respiratory rate. During telemetry monitoring, the same monitoring items as vital signs or 12 Lead- ECG can be monitored once. Adherence to the intervention will be done via Drug Accountability.
Sponsors
Accendatech AU Pty Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects, 18-55 years of age (both inclusive) at the time of screening. 2. Subjects able to provide a signed and dated informed consent and/or assent document indicating that the subject has been informed of all pertinent aspects of the study before any assessment is performed. 3. Subjects who agree to comply with protocol restrictions, including refraining from consuming alcohol, caffeinated beverages (e.g., tea, coffee, etc.), and tobacco or nicotine containing products from 24 hours before Day 1 until the last PK blood sample collection is finished; able to remain in house for the confinement period of the study without interruption. 4. Body mass index (BMI, weight [kg]/height2 [m2]) within 18.0-28.0 kg/m2 (both inclusive). 5. A female participant is eligible to participate if she is not pregnant and intending to become pregnant or breastfeeding, and at least one of the following conditions applies:- surgically sterile (by means of hysterectomy and/or bilateral oophorectomy) or post-menopausal for atleast one year, defined as amenorrhea for 12 consecutive months without another cause and with a follicle stimulating hormone (FSH) level greater than or equal to 40 mIU/mL at screening.- a woman of childbearing potential and using a contraceptive method that is highly effective, with a failure rate of less than 1%, during the treatment period and for at least 1 month after the last dose of study treatment. 6. Male subjects must be willing to remain abstinent (when this is in line with their preferred and usual lifestyle), or, if engaging in sexual intercourse with a female partner of childbearing potential, willing to use a condom in addition to having the female partner use a highly effective method of female contraception from the time of the first study drug administration until 30 days following the last dose of study drug. This requirement does not apply to subjects in a same-sex relationship, subjects with female partners of non-childbearing potentials, or vasectomized subjects who have not undergone any reversal procedure. Male subjects must also be willing to not donate sperms from the time of the first study drug administration until 30 days after the last dose of study drug. 7. No clinically significant abnormal values on vital signs, B-ultrasound and 12-lead ECG. QT interval corrected for heart rate according to Fridericia's formula (QTcF) must be within the following ranges: QTcFless than or equal to 450 msec for male subjects, and QTcF less than or equal to 470 msec for female subject. Assessment may be repeated once if deemed appropriate by the Investigator. 8. No clinically significant abnormal findings noted during screening for medical history and physical examination, or clinically significant abnormal results during screening clinical laboratory tests, including white blood cells (WBCs), liver function and kidney function. Assessment may be repeated once if deemed appropriate by the Investigator. 9. Negative urine drug screen and alcohol breath testing at screening and on Day -1. 10. Ability to swallow all study drugs.
Exclusion criteria
1. Subjects who have a clinically relevant intolerance or allergy to drugs, or are known or suspected to have hypersensitivity to any ingredient in the study drugs 2. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs 3. History or clinical manifestations of any clinically significant gastrointestinal, renal, urologic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder or cancer, at the discretion of the Investigator 4. Current or chronic history of liver disease or known hepatic or biliary abnormalities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin greater than upper limit of normal (ULN) 5. Current or history of clinically significant cardiac arrhythmias (symptomatic or asymptomatic) 6. Subjects who have had any significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration. Subjects with a mild upper respiratory infection may be enrolled at the discretion of the Investigator; 7. Creatinine clearance less than 90 mL/min (using the Cockcroft-Gault method based on serum creatine and actual body weight) at screening 8. Major illness or surgery (except for minor outpatient surgery) within past 3 months of study Day 1, or planned surgery during the study period 9. Intolerance to direct venepuncture 10. Participation in any clinical study with an investigational drug, biologic or device within 4 weeks or 5 times the half-life of the specific product if applicable (whichever is longer) since the last dosing or the last use of the investigation drug, biologic or device, prior to the first dosing of ACT004; 11. Donated blood greater than 400 mL or significant blood loss equivalent to 400 mL, or received blood transfusion within 1 months of screening, or have plans to donate blood during the study; 12. History of malignancy within 5 years of screening visit (excluding non-melanoma skin cancer that has been resected); 13. Positive test at screening of any of the following: serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV RNA or HCV Ab) or human immunodeficiency virus 1 and 2 (HIV Ab); 14. Recent administration or plans to receive administration of any live vaccine within 12 weeks before Day 1; 15. Use of any other drug, including prescription and over-the-counter medications, within one week of first dosing or within 5 times the elimination half-life of the medication (whichever is longer) prior to first dosing. Exceptions may be made on a case-by-case basis following discussion and agreement between the Investigator and the sponsor. • Paracetamol at a dose of less than 2 g in 24 hours but no more than 1 g in 4 hours is permitted; • Dietary vitamins may be allowed at the discretion of the Investigator (e.g. vitamin D taken at a standard replacement dose and at a time remote from IP drug administration); • Herbal supplements are not permitted 16. Unwilling to refrain from caffeinated beverages (i.e., tea, coffee, etc.) from 24 hours before Day -1 until completion of the confinement period. 17. Use of food or beverages likely to influence liver metabolism or inhibit CYP2C9, within 14 days prior to the first dose of the study drug (e.g., star fruit, pomelos, grapefruit & Seville oranges) 18. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week for female subjects and 21 units of alcohol per week for male subjects (1 Unit = 360 mL of beer or 45 mL of alcohol 40% or 150 mL of wine) and, unwilling to refrain from consumption of alcohol from 24 hours before Day -1 until completion of the confinement period 19. Use of tobacco or nicotine products or smoking within 30 days (more than 5 cigarettes per day) prior to screening, and, unwilling to refrain from 24 hours before Day -1 until completion of the confinement period 20. Known or suspected history of drug abuse (e.g., amphetamines [AMP], Methamphetamines [MET], methadone [MTD], barbiturates [BAR], benzodiazepines [BZO], cocaine [COC], opiates [OPI], methyl enedioxy, methamphetamine [MDMA], phencyclidine [PCP], tetrahydrocannabinol [THC]) within the past 2 years or presence of drug abuse within 3 months before screening, or evidence of such abuse on laboratory assays at screening unless explained by a therapeutic dose of a prescribed medication that was ceased at least 14 days prior to Day 1. Drug screening may be repeated once at the discretion of the Investigator 21. Pregnant (positive pregnancy test) or lactating women 22. Any factor, which in the opinion of the Investigator would jeopardize the evaluation or safety or be associated with poor adherence to the protocol, rendering the subject unsuitable for participating in the study.
Outcome results
None listed