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Trial registered on ANZCTR


Registration number
ACTRN12623000243617
Ethics application status
Approved
Date submitted
23/02/2023
Date registered
7/03/2023
Date last updated
12/06/2024
Date data sharing statement initially provided
7/03/2023
Date results information initially provided
12/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Effects of Food on Pharmacokinetics of AC-101
Scientific title
A Single Center, Randomized, open label, two-period, cross over study to evaluate the effects of food on the Pharmacokinetics of AC-101
Secondary ID [1] 309030 0
AC-101-AU-PhIa
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12623000234617p

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 329087 0
Condition category
Condition code
Oral and Gastrointestinal 326061 326061 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Accro Bioscience is developing AC-101, a potent and selective oral small molecule inhibitor of RIPK2, indicated for treatment of inflammatory bowel disease (IBD).
Investigational Product (IP): AC-101
Dose: 100 mg
Dosage Form: Tablet
Mode of Administration: Oral
An open panel of 12 subjects will receive single dose of 100 mg of AC-101 under both fed and fasted conditions in a two-period crossover study. In the study, 6 subjects will receive a single administration of AC-101 under fasted condition in period 1 Day 1 and receive another administration of AC-101 after a high-fat meal in period 2 Day 5, after a wash out period of 3 day. For the other 6 subjects, the administration of AC-101in period 1 will be carried out under a fed condition, the administration of AC-101 in period 2 will be carried out at fasted condition.
The subjects will have a total of 7 overnight stays (admission on Day -1 until Day 7) and will have a follow up visit on Day 14.
A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal will provide to the subject 30 min prior to dosing. This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively.
The participants are dosed at the site, they will receive study treatment directly from the Investigator or designee, under medical supervision. Immediately after dose administration, visual inspection of the mouth and hands will be performed for each subject. The date and time of each dose administered will be recorded in the source documents. The dose of study treatment and study participant identification will be confirmed at the time of dosing by a member of the study site staff other than the person administering the study treatment.
Intervention code [1] 325475 0
Treatment: Drugs
Comparator / control treatment
Fasted Condition
Control group
Active

Outcomes
Primary outcome [1] 333925 0
To evaluate the safety and tolerability of AC-101 as assessed by,
- Incidence and severity of adverse events (AE) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA version 25.1)
- Clinically significant changes from baseline in laboratory evaluations (hematology, blood biochemistry, urine routine and coagulation function tests)
- 12-lead Electrocardiograms (12-lead ECGs)
- Vital signs (Vital Sign monitor is used to measure systolic/diastolic Blood Pressure, pulse rate and oxygen saturation, respiratory rate is measured manually by the medical staff using clock, oral temperature is measured using tympanic thermometer)
- Physical examinations includes weight is measured weighing scales, general observations, skin examination, lymph nodes examination, head and neck examination, examinations for cardiac, respiratory, abdominal and neurological system
Timepoint [1] 333925 0
Adverse Events:
Part 2 Food Effect - Daily from Screening to Day 14

Clinical Laboratory tests (hematology, blood biochemistry, urine routine and coagulation function tests):
Part 2 Food Effect - Screening, on Day -1, Day 2, Day 3, Day 6, Day 7, hematology, liver, kidney function panel will be tested on Day 14.

12-lead ECGs:
Part 2 Food Effect - Screening, on Day -1, and on Day 1, Day 5 pre-dose and at 30 min, 1h, 2h, 24h, 48h post-dose.

Vital Signs:
Part 2 Food Effect - Screening, on Day -1, pre-dose and on Day 1 and Day 5 at 30 min, 1h, 2h, 24h, 48h post-dose, Day 14

Physical Examination:
Part 2 Food Effect - Screening, on Day -1, Day 2, Day 3, Day 6, Day 7, Day 14 post-dose.
Secondary outcome [1] 418768 0
To characterize the pharmacokinetics (PK), and determine the effects of food on PK of AC-101 following oral administration by collecting blood samples. The parameters for PK assessment are:
- Maximum observed plasma concentration (Cmax)
- Time of maximum observed plasma concentration (Tmax)
- Terminal Phase Elimination Half Life (t1/2)
- Area under the plasma concentration curve from time 0 to last (AUC0-last)
- Area under the plasma concentration curve from time 0 to infinity (AUCinf)
- Area under the plasma concentration curve from time to 0 to t (AUC0-t)
- Mean residence time (MRT)
- Apparent clearance (CL/F)
- Apparent volume of distribution (Vz/F)
- Apparent Terminal Rate Constant (kel)
- Minimum drug concentration at steady-state (Cmin,ss)
- Maximum plasma concentration at steady state (Cmax,ss)
- Average plasma drug concentration during a dosing interval at steady-state (Cav,ss)
- steady-state fluctuation coefficient (DF)
- accumulation ratio (rac)
Timepoint [1] 418768 0
Pre-dose (within 1h prior to dosing) and on Day 1 and Day 5 at 15±1 min, 30±2 min, 45±2 min, 1 h±4min, 1.5 h±4 min, 2 h±4 min, 4 h±10 min, 8 h±10 min, 12 h±30 min, 24 h± 30min and 48 h± 30min post-dose.

Eligibility
Key inclusion criteria
1. Are capable of giving informed consent and complying with study procedures.
2. The age between 18 and 60 years, inclusive.
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg for male and 45 kg for female.
4. Female subjects have a negative serum pregnancy test result at screening and Day -1, and meet one of the following criteria:
• Using highly effective method of contraception such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS) at least 1 month prior to screening and willing to continue the control for the duration of the study, and until 3 months after dosing with the study drug.
• Surgically sterile for at least 3 months prior to screening by one of the following means:
- Bilateral salpingectomy (with or without oophorectomy)
- Surgical hysterectomy
- Vasectomized partner
- Bilateral oophorectomy (with or without hysterectomy)
• Postmenopausal, defined as the following:
- Last menstrual period greater than 12 months prior to screening
- Postmenopausal status confirmed by serum follicle stimulating hormone (FSH) level of greater than or equal to 40 IU/L at screening.
5. Male subjects with female partners of child bearing potential must agree to use condoms and use highly effective method of contraception with female partner for the duration of the study and until 3 months after dosing with the study drug and must refrain from donating sperm for this same period.
6. Subjects who are exclusively in same-sex relationships (contraception is not required for female participants who are in same-sex) and subjects who abstain completely for the duration of the study and for 3 months after the last study treatment are acceptable;
7. Considered healthy by the Investigator, based on subject’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
8. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Evidence of clinically significant hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal (GI), hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies or food intolerances; mild and inactive hay fever is permitted), or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug; or place the subject at an unacceptable risk as a participant in this study;
2. Has had an acute illness considered clinically significant by the Investigator within 30 days prior to screening, minor colds are permitted;
3. Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range at screening and Check-in and considered clinically significant in the opinion of the Investigator. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator.
4. Taken any drug that inhibits or induces liver drug-metabolizing enzymes 30 days prior to screening; Excessive consumption of special diets (including dragon fruit, mango, grapefruit, grapefruit juice, pomelo, star fruit, Seville oranges, Seville orange marmalade or other products containing grapefruit, pomelo, star fruit or Seville oranges etc.) and/or xanthine-rich diets (including chocolate, tea, coffee, cola, etc.) or other effects that affect the absorption, distribution, metabolism, excretion and other factors of the drug 7 days prior to study drug administration;
5. Clinically significant history with sequelae of gastrointestinal tract, liver, kidney, or other diseases known to interfere drug absorption, distribution, metabolism or excretion.
6. Prolongation of QTcF (greater than 450 msec for males and greater than 470 msec for females) at screening.
7. Known current or history of malignancy.
8. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or human immunodeficiency virus (HIV) antibody.
9. A hospital admission or major surgery within 90 days prior to screening.
10. A history of prescription drug abuse, or illicit drug use within 3 months prior to screening.
11. A history of alcohol abuse according to medical history within 3 months prior to screening.
12. Has more than 5 cigarettes/week within 30 days prior to screening or intends to use any product containing nicotine during the course of the study;
13. A positive screen for alcohol, cotinine, and/or drugs of abuse at screening or Day -1.
14. An unwillingness or inability to comply with food and beverage restrictions during study participation (ie lactose intolerance; vegans and vegetarians are permitted in Part 1 and 3), and refrain from ingestion of dragon fruit, mango, grapefruit, grapefruit juice, pomelo, star fruit, Seville oranges, Seville orange marmalade or other products containing grapefruit, pomelo, star fruit or Seville oranges from 7 days prior to study drug administration to the end of the study;
15. Has had any immunizations (live vaccines) in the 4 weeks prior to screening.
16. Has used medications that affect GI motility or gastric emptying within 30 days prior to Day 1.
17. Has used any prescription or over-the-counter medication (with exception of acetaminophen at less than 2 g/day until 48 hours prior to dosing), vitamins/herbal supplements (with the exception of hormonal contraceptives) within 14 days or 5 half-lives of the drug (whichever is longer) prior to Day 1.
18. Poor venous access.
19. Has lost or donated greater than 450 mL of whole blood or blood products within 30 days prior to screening.
20. Taken any investigational drug within 30 days, or 5 half-lives whichever is longer.
21. Female who are pregnant, or breastfeeding, Positive pregnancy test result.
22. Any condition or finding that in the Investigators’ opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
24/05/2023
Date of last participant enrolment
Anticipated
15/05/2023
Actual
20/06/2023
Date of last data collection
Anticipated
2/11/2024
Actual
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24077 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 39586 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 313238 0
Commercial sector/Industry
Name [1] 313238 0
Accro Bioscience (Australia) Pty Ltd
Country [1] 313238 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Accro Bioscience (Australia) Pty Ltd
Address
Level 7, 330 Collins Street, Melbourne Victoria 3000
Country
Australia
Secondary sponsor category [1] 314964 0
None
Name [1] 314964 0
Address [1] 314964 0
Country [1] 314964 0
Other collaborator category [1] 282567 0
Commercial sector/Industry
Name [1] 282567 0
Novotech (Australia) Pty Limited
Address [1] 282567 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282567 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312467 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 312467 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 312467 0
Australia
Date submitted for ethics approval [1] 312467 0
23/01/2023
Approval date [1] 312467 0
02/03/2023
Ethics approval number [1] 312467 0

Summary
Brief summary
This is open label, cross over study to evaluate the safety, tolerability, pharmacokinetics (PK) food effects of AC-101 following oral single/multiple ascending dose administration in healthy male and female participants. The impact of food (high-fat breakfast) on the rate and extent of absorption will be evaluated. Food Effect (FE) study enrolling 1 cohort of subjects (Part 2) to receive AC-101 under both fasted and fed conditions for investigating the effect of food.
In this part of the study the dose given in Fed Period will be administered 30 minutes after starting a high-fat breakfast.
A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal will provide to the subject 30 min prior to dosing. This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124774 0
Dr Ofer Gonen
Address 124774 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria,
Australia
Country 124774 0
Australia
Phone 124774 0
+61 0385939800
Fax 124774 0
Email 124774 0
o.gonen@nucleusnetwork.com.au
Contact person for public queries
Name 124775 0
Dr Ofer Gonen
Address 124775 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria,
Australia
Country 124775 0
Australia
Phone 124775 0
+61 0385939800
Fax 124775 0
Email 124775 0
o.gonen@nucleusnetwork.com.au
Contact person for scientific queries
Name 124776 0
Mr Xiaohu Zhang
Address 124776 0
Accro Bioscience (Australia) Pty Ltd
Level 7, 330 Collins Street, Melbourne, Victoria, Australia 3000
Country 124776 0
Australia
Phone 124776 0
+61451332620
Fax 124776 0
Email 124776 0
xiaohu.zhang@accro.com.cn

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.