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Trial registered on ANZCTR


Registration number
ACTRN12623000256673
Ethics application status
Approved
Date submitted
16/01/2023
Date registered
9/03/2023
Date last updated
9/03/2023
Date data sharing statement initially provided
9/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
PART C - A Phase I, Randomized, Open-label, Cross-over Study to Evaluate the Pharmacokinetics of Food Effect of ACT004 in Healthy Adult Subjects.
Scientific title
PART C - A Phase I, Randomized, Open-label, Cross-over Study to Evaluate the Pharmacokinetics of Food Effect of ACT004 in Healthy Adult Subjects.
Secondary ID [1] 308192 0
NA
Universal Trial Number (UTN)
NA
Trial acronym
Linked study record
Linked to ACTRN12622001507774 (Part A and B)

Health condition
Health condition(s) or problem(s) studied:
Kidney Fibrosis 327933 0
Condition category
Condition code
Renal and Urogenital 325001 325001 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 325096 0
Treatment: Drugs
Comparator / control treatment
Postprandial - fasting condition
Control group
Active

Outcomes
Primary outcome [1] 333171 0
Evaluate the pharmacokinetics (PK) characteristics of ACT004 after administration and food effect (FE) of ACT004 in healthy adult subjects.
Pharmacokinetic parameters of ACT004 including but not limited to, maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf), area under the plasma concentration-time curve from time 0 to the time t of last quantifiable concentration (AUC0-t), apparent volume of distribution (Vd/F), elimination half-life (t1/2),clearance (CL/F), mean residence time (MRTinf), and elimination rate constant (Lambda-z) will be evaluated.
Timepoint [1] 333171 0
PK blood samples will be collected on Day 1 at Predose (-1 to 0 hour), 0.25 hour, 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour post dose, Day 2, Day 6 Predose (-1 to 0 hour), 0.25 hour, 0.5 hour, 1 hour, 2 hour,3 hour, 4 hour, 6 hour, 8 hour and 12hours and on Day 7. The PK sampling time point on Day 2 corresponds to the point 24 hours after dosing on Day 1. The PK sampling time point on Day 7 corresponds to the point 24 hours after dosing on Day 6. The PK sampling times might need to be adjusted for subsequent cohorts in order to better characterize PK profile of ACT004.
Secondary outcome [1] 417731 0
N/A
Timepoint [1] 417731 0
N/A

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Pharmacokinetic parameters will be analyzed by standard non-compartmental methods with Phoenix WinNonlin.
Plasma concentration-time profiles will be obtained by plotting mean concentrations against blood sampling time points. Plasma concentrations at each blood sampling time point are subject to descriptive statistical analysis.
Pharmacokinetic data will be presented in graphical and/or tabular form and will be summarized descriptively. Summary statistics including number, arithmetic mean, median, SD, minimum, maximum, geometric mean and coefficient of variation, will calculate for all PK measures.
Descriptive statistical analyses will be performed for PK parameters by cohorts.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2023
Actual
Date of last participant enrolment
Anticipated
1/11/2023
Actual
Date of last data collection
Anticipated
13/11/2023
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23611 0
Nucleus Network - Geelong
Recruitment hospital [2] 23612 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 39030 0
3004 - Melbourne
Recruitment postcode(s) [2] 39031 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 312447 0
Commercial sector/Industry
Name [1] 312447 0
Accendatech AU Pty Ltd.
Country [1] 312447 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Accendatech AU Pty Ltd.
Address
Accendatech AU Pty Ltd.
Suite 2903, 201 Elizabeth St. Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 314025 0
Commercial sector/Industry
Name [1] 314025 0
Avance Clinical Pty Ltd
Address [1] 314025 0
Avance Clinical Pty Ltd
Level 1, Ann Nelson Drive
Thebarton, SA 5031, Australia
Country [1] 314025 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311793 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311793 0
55 commercial Road, Melbourne, VIC 3004
Australia
Ethics committee country [1] 311793 0
Australia
Date submitted for ethics approval [1] 311793 0
31/08/2022
Approval date [1] 311793 0
31/10/2022
Ethics approval number [1] 311793 0

Summary
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).
Trial website
Trial related presentations / publications
Public notes
This is the first clinical study of ACT004 to evaluate the safety, tolerability and PK profile in a population. The selection of healthy adult volunteers for this human study meets ethical requirements. At the same time, the sample homogeneity of healthy people is high, which can reduce the influence of individual differences on safety and PK characteristics results; on the other hand, selecting healthy people can avoid the impact of disease burden and concomitant medications on the safety evaluation of experimental drugs, and healthy people can help researchers observe more reliable toxicity data. This study is also randomized and double-blinded with regard to treatment with ACT004 and matching placebo in order to prevent bias in treatment allocation and in the assessment of effect. The Investigator, as well as the Sponsor and their representatives involved in the monitoring or conducting the study, and the subjects will all be blinded to the study drug codes.

Contacts
Principal investigator
Name 122386 0
Dr Sam Francis
Address 122386 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 122386 0
Australia
Phone 122386 0
+61 737072720
Fax 122386 0
Email 122386 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 122387 0
Ms Nucleus Network Melbourne
Address 122387 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 122387 0
Australia
Phone 122387 0
+61 1800243733
Fax 122387 0
Email 122387 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 122388 0
Dr Sam Francis
Address 122388 0
Dr Sam Francis
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 122388 0
Australia
Phone 122388 0
+61 385939800
Fax 122388 0
Email 122388 0
s.francis@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and Intellectual property rights considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.