Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000408684
Ethics application status
Approved
Date submitted
13/04/2023
Date registered
24/04/2023
Date last updated
17/04/2024
Date data sharing statement initially provided
24/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to Evaluate the Effects of Food on Pharmacokinetics of AC-201.
Scientific title
A Single Center, Randomized,open label,two-period,cross over study to evaluate the effects of Food on Pharmacokinetics of AC-201 (Part 2)
Secondary ID [1] 309454 0
AC-201-AU-PhIa
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12623000375651
This record is a sub-study of this study.

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 329706 0
Condition category
Condition code
Skin 326606 326606 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Accro Bioscience is developing AC-201, a potent and selective oral small molecule inhibitor of tyrosinekinase 2 (TYK2) and JAK1, indicated for treatment of the moderate-to-severe plaque psoriasis.
Investigational Product(IP):AC-201
Dose:50 mg
Dosage Form:Tablet
Mode of Administration:Oral
An open panel of 12 subjects will receive single dose (50 mg) of AC-201 under both fed and fasted conditions in a two-period crossover study.
In the study,6 subjects will receive a single administration of AC-201 under fasted condition in period 1,and receive another administration of AC-201 after a high-fat meal in period 2, after a washing out period.For the other 6 subjects, the administration of AC-201 in period 1 will be carried out under a fed condition,the administration of AC-201 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).
Regarding the high-fat meal, the FDA high-fat breakfast will be provided to the subjects 30min prior to dosing.
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 30min prior to dosing.This test meal should derive approximatly 150,250 and 500-600 calories from protein,carbihydrate,and fat,respectively.
The participants are dosed at the site, they will receive study treatment directly from the Investigator or designee, under medical supervision. lmmediately after dose administration,visual,inspection of the mouth and hands will be performed for each subject. The date and time of eachdose 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 otherthan the person administering the study treatment.
Intervention code [1] 325876 0
Treatment: Drugs
Comparator / control treatment
Fasted Condition

minimum of 10 hour fast.It is a full fasting. Participants will not be allowed to have water; or nil by mouth, etc
Control group
Active

Outcomes
Primary outcome [1] 334459 0
To evaluate the safety and tolerability of AC-201 following oral dose administration assessed by:
- lncidence and severity of adverse events (AE) will be coded using the Common Terminology Criteria for Adverse Events (CTCAE5.0)
- Clinically significant changes from baseline in laboratory evaluations(hematology, blood biochemistry, urine routine and coagulation function). The blood sample and urine sample need collected from participants for laboratory evaluations;
-12-lead Electrocardiograms (12-lead ECGs)
- Vital signs(include blood pressure, pulse rate, respiratory rate, tympanic temperature.)
Blood pressure assessed using a sphygmomanometer
Pulse rate and Resp rate is measured manually by the medical staff using clock. Temperature is measured using tympanic thermometer.
- Physical examinations(General Appearance, HEENT(Head, Eyes, Ears, Nose, and Throat), Mouth/Dental, Neck (include Thyroid & Nodes), Cardiovascular, Respiratory, Gastrointestinal, Renal, Neurological, Musculoskeletal, Skin,)
Timepoint [1] 334459 0
Adverse Events:
Part 2 FE - Daily from Screening,on Day1,Day2, Day3,Day4,Day5,Day6,Day 7

Clinical Laboratory tests (hematology, chemistry, coagulation, and urinalysis)
Part 2 FE - screening, on Day-1, Day 2, Day 7 post-dose

12-lead ECGs:
Part 2 FE-Screening, on Day -1, Day 1, Day 5 pre-dose (within 1h prior to dosing) and at 30min, 1h, 2h, 24h, 48h post-dose.

Vital Signs:
Part 2 FE-screening, on Day -1, Day 1 , Day 5 pre-dose (within 1h prior to dosing) and at 30min, 1h, 2h, 24h, 48h post-dose.

Physical Examination:
Part 2 FE-screening ,on Day 7.
Secondary outcome [1] 420783 0
• To characterize the pharmacokinetics (PK) and determine the effects of food on PK of AC-201 following oral single dose of AC-201.
The drug concentrations of AC-201 in plasma; the main pharmacokinetic parameters:
- 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 (AUCo-last)
- Area under the plasma concentration curve from time o to infinity (AUCinf)
- Area under the plasma concentration curve from time to o to t (AUCo-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] 420783 0
PK:pre-dose (within 1h prior to dosing) and on Day 1 and Day 5 at 15min, 30min, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h post-dose.

Eligibility
Key inclusion criteria
1. Are capable of giving informed consent and complying with study procedures;
2. Are between the ages of 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, and no more than 120 kg;
4. Female subjects have a negative serum pregnancy test result at screening and a negative urine pregnancy test result Day -1, and meet one of the following criteria:
• Using highly effective method of contraception such as implants, injectables, oral contraceptives, intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS) at least 3 months prior to screening and willing to continue the control for the duration of the study and until 1 month 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 is
greater than or equal to 30 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;
6. Subjects who are exclusively in same-sex relationships and abstain completely for the duration of study and 3 months after the last study treatment are exempt from the contraceptive requirements;
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, Gilbert’s Syndrome and allergic disease (including multiple clinically significant drug allergies or food intolerances; mild and inactive hayfever is permitted), or any other condition, 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; resolved childhood asthma, non-hospitalised depression and migraines are not exclusionary unless deemed clinically significant by the investigator;
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. Subjects must be excluded who meet the following laboratory values at the screening visit: Hb<115g/L (Female) and HB<125g/L (Male); Serum creatinine>1.5xULN; Aspartate aminotransferase >1.5xULN; Alanine aminotransferase >1.5xULN; Total bilirubin>1.5xULN; Triglycerides >2mmol/L. 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 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 2 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 (appendicectomy allowed if uncomplicated, hernia surgery allowed if small and no bowel resection, cholecystectomy excluded, bariatric surgery including gastric banding excluded);
6. Prolongation of QTcF (>450 msec for males and >470 msec for females) at screening;
7. eGFR <80mL/min calculated using Cockroft & Gault formula;
8. Cancer or history of lymphoproliferative disease within last 5 years; exception is resected cutaneous basal cell or squamous cell carcinoma that has been treated without recurrence;
9. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or human immunodeficiency virus (HIV) antibody;
10. A hospital admission or major surgery within 90 days prior to screening;
11. A history of prescription drug abuse, or illicit drug use within 3 months prior to screening;
12. A history of alcohol abuse according to medical history (drinking 4 or more standard drinks (a standard drink equals 10 g of pure alcohol) on any day for women and drinking 5 or more standard drinks on any day for men) within 3 months prior to screening;
13. Has more than 10 cigarettes/week within 30 days prior to screening or intends to use any product containing nicotine during the course of the study;
14. A positive screen for alcohol, and/or drugs of abuse at screening or Day -1; A positive screen for cotinine on Day -1; A repeat is allowed at investigator discretion for suspected false positive;
15. Unwilling to 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 or red wine from 7 days prior to study drug administration to the end of the study;
16. Has had any immunizations in the 2 weeks prior to screening;
17. Has used medications that affect GI motility or gastric emptying within 30 days prior to Day 1; or the participants with clinically significant abnormal bowel habits by the Investigator’s opinion, including symptoms of cramping, abdominal pain, bloating, gas, diarrhea and/or constipation;
18. Has used any prescription or over-the-counter medication (with exception of acetaminophen at < 2 g/day is permitted until 48 hours prior to dosing), vitamins/herbal supplements (with the exception of hormonal contraceptives) within 7 days or 5 half-lives of the drug (whichever is longer) prior to Day 1;
19. Poor venous access;
20. Has lost or donated >450 mL of whole blood or blood products within 30 days prior to screening;
21. Taken any investigational drug within 30 days or 5 half-lives whichever is longer;
22. Female who are pregnant or breastfeeding; Positive pregnancy test result;
23. Intending to donate sperm or ova during the study and three months after the end of treatment;
24. 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
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Participant recruitment difficulties, the sponsor has decided to terminate the study in Australia due to a significant recruitment delay that impacted on overall project timeline.
Date of first participant enrolment
Anticipated
5/06/2023
Actual
26/06/2023
Date of last participant enrolment
Anticipated
23/10/2023
Actual
13/10/2023
Date of last data collection
Anticipated
30/11/2023
Actual
16/10/2023
Sample size
Target
12
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 24514 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 40103 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 313650 0
Commercial sector/Industry
Name [1] 313650 0
Accro Bioscience (Australia) Pty Ltd
Country [1] 313650 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] 315442 0
None
Name [1] 315442 0
Address [1] 315442 0
Country [1] 315442 0
Other collaborator category [1] 282628 0
Commercial sector/Industry
Name [1] 282628 0
Novotech (Australia) Pty Limited
Address [1] 282628 0
Level 3, 235 Pyrmont Street,Pyrmont NSW 2009
Country [1] 282628 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312818 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 312818 0
Ethics committee country [1] 312818 0
Australia
Date submitted for ethics approval [1] 312818 0
29/03/2023
Approval date [1] 312818 0
12/05/2023
Ethics approval number [1] 312818 0
2023-03-332

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126026 0
Dr Alex Choo
Address 126026 0
CMAX Clinical Research Pty Ltd,
Level 5,21North Terrace, Adelaide, South Australia,5000
Country 126026 0
Australia
Phone 126026 0
+61870887900
Fax 126026 0
Email 126026 0
[email protected]
Contact person for public queries
Name 126027 0
Alex Choo
Address 126027 0
CMAX Clinical Research Pty Ltd,
Level 5,21North Terrace, Adelaide, South Australia,5000
Country 126027 0
Australia
Phone 126027 0
+61870887900
Fax 126027 0
Email 126027 0
[email protected]
Contact person for scientific queries
Name 126028 0
Xiaohu Zhang
Address 126028 0
Accro Bioscience (Australia) Pty Ltd
Level 7, 330 Collins Street, Melbourne Victoria 3000
Country 126028 0
Australia
Phone 126028 0
+61451332620
Fax 126028 0
Email 126028 0
[email protected]

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.