Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001038684
Ethics application status
Approved
Date submitted
26/08/2023
Date registered
26/09/2023
Date last updated
1/09/2024
Date data sharing statement initially provided
26/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A drug-drug interaction trial between AR882, fluconazole, carbamazepine, celecoxib, and sulfasalazine in healthy particpants
Scientific title
A Phase 1, Open-Label Trial to Evaluate the Potential Drug-Drug Interactions of AR882 with CYP2C9 Inhibitor, Inducer, and Substrate, and BCRP Substrate in Healthy Adult Participants
Secondary ID [1] 310452 0
AR882-105
Universal Trial Number (UTN)
U1111-1297-0592
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 331238 0
Condition category
Condition code
Inflammatory and Immune System 327997 327997 0 0
Other inflammatory or immune system disorders
Musculoskeletal 328185 328185 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted at two study centers. There will be 5 treatment groups with up to 14 participants per treatment group. Treatment Groups 1 to 5 may be conducted in parallel.
Dosing: Participants will orally ingest Investigational Product (IP) after an overnight fast of at least 10 hours and will remain fasted until at least 4 hours post-dose. Subjects may ingest water ad libitum during the period of fasting before and after IP administration except 1 hour before dosing and up to 1 hour post-dosing. All participants will be observed at the time of dosing by site staff to confirm ingestion of the study drug. Participants will be allocated to each group in the following manner, 1st 10 eligible participants will dose in Group 3, next 10 eligible participants will dose in Group 1, the next 10 eligible participants will dose in Group 4, the next 10 eligible participants will dose in Group 2, and the next 14 eligible participants will dose in Group 5.
Segment A (CYP2C9 Evaluation):
Group 1: AR882 (50 mg) oral capsule once daily on Days 1 and 8; AND Fluconazole (400 mg) (oral capsule) on Day 7, then 200 mg on Days 8 and 9
Group 2: AR882 (75 mg) oral capsule once daily on Days 1 and 20; AND Carbamazepine 200 mg (solid oral tablet) per day on Days 7 to 9, then 400 mg per day on Days 10 to 12, then 600 mg per day on Days 13 to 21
Group 3: AR882 (75 mg) oral capsule once daily on Days 4 to 6; AND Celecoxib 200 mg (oral capsule) on Days 1 and 5
Segment B (BCRP Evaluation):
Group 4: AR882 (75 mg) once daily on Days 4 to 6; AND Sulfasalazine 500 mg (solid oral tablet) on Days 1 and 5
Group 5: AR882 (75 mg) oral capsule once daily on Days 1 and 22; AND Carbamazepine 200 mg (solid oral tablet) per day on Days 6 to 8, then 400 mg per day on Days 9 to 15, then 600 mg per day on Days 16 to 23
Intervention code [1] 326850 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335856 0
To evaluate the potential effect of fluconazole, a CYP2C9 inhibitor, on the plasma PK of AR882 in healthy adult participants. Plasma PK parameters Cmax, Tmax, AUClast, AUC0-inf, t1/2 will be summarized for AR882 by descriptive statistics (Group 1)
Timepoint [1] 335856 0
Plasma PK parameters will be assessed at the below timepoints
Day 1: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose.
Days 2 to 6: 24, 36, 48, 72, 96, and 120 hours post Day 1 dose.
Day 8: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose.
Days 9 to 13: 24, 36, 48, 72, 96, and 120 hours post Day 8 dose.
Primary outcome [2] 335857 0
To evaluate the potential effect of carbamazepine, a CYP2C9 inducer, on the plasma PK of AR882 in healthy adult participants. Plasma PK parameters Cmax, Tmax, AUClast, AUC0-inf, t1/2 will be summarized for AR882 by descriptive statistics (Group 2 and Group 5)
Timepoint [2] 335857 0
Plasma PK parameters will be assessed at the below timepoints Day 1 (Group 2 and Group 5): Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose. Days 2 to 6: 24, 36, 48, 72, 96, and 120 hours post Day 1 dose. Day 20 (Group 2) or Day 22 (Group 5): Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose. Days 21 to 25: 24, 36, 48, 72, 96, and 120 hours post Day 20 dose.
Primary outcome [3] 335858 0
To evaluate the potential effect of AR882 as a CYP2C9 inhibitor on the plasma PK of celecoxib in healthy adult participants. Plasma PK parameters Cmax, Tmax, AUClast, AUC0-inf, t1/2 will be summarized for celecoxib by descriptive statistics (Group 3)
Timepoint [3] 335858 0
Plasma PK parameters will be assessed at the below timepoints for Group 3
Day 1: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose.
Days 2 to 3: 24, 36 and 48 hours post Day 1 dose.
Day 5: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose.
Day 6 to Day 7: 24, 36, and 48 hours post Day 5 dose.
Secondary outcome [1] 425907 0
To evaluate the safety of AR882 with and without concurrent administration of fluconazole (Group 1), carbamazepine (Group 2 and Group 5), celecoxib (Groupd 3), or sulfasalazine (Group 4) in healthy adult participants. Outcomes assessed: ECG performed by qualified site staff using a calibrated electrocardiogram machine, physical exam performed by qualified site staff, vital signs (pulse rate, blood pressure, respiratory rate, temperature) collected using a sphygmomanometer, a thermometer, and a clock by qualified site staff, safety laboratory measures collected by way of venipuncture and urine sample collection and performed by qualified site staff.
Timepoint [1] 425907 0
Group 1: Monitored from pre-dose through Day 20 (Follow-up); frequency of assessments: Day -1, Day 1, Day 7, Day 10, Day 20. Group 2: Monitored from pre-dose through Day 32 (Follow-up); frequency of assessments: Day -1, Day 1, Day 3, Day 6, Day 19, Day 22, Day 32 Group 3: Monitored from pre-dose through Day 13 (Follow-Up); frequency of assessments: Day -1, Day 1, Day 4, Day 7, Day 13 Group 4: Monitored from pre-dose through Day 13 (Follow-Up); frequency of assessments: Day -1, Day 1, Day 4, Day 7, Day 13 Group 5: Monitored from pre-dose through Day 33 (Follow-Up); frequency of assessments: D-1, Day 1, Day 3, Day 6, Day 8, Day 13, Day 18 through Day 24, Day 27, and Day 33
Secondary outcome [2] 425908 0
To evaluate the tolerability of AR882 with and without concurrent administration of fluconazole (Group 1), carbamazepine (Group 2 and Group 5), celecoxib (Groupd 3), or sulfasalazine (Group 4) in healthy adult participants. Outcomes assessed: ECG performed by qualified site staff using a calibrated electrocardiogram machine, physical exam performed by qualified site staff, vital signs (pulse rate, blood pressure, respiratory rate, temperature) collected using a sphygmomanometer, a thermometer, and a clock by qualified site staff, safety laboratory measures collected by way of venipuncture and urine sample collection and performed by qualified site staff.
Timepoint [2] 425908 0
Group 1: Monitored from pre-dose through Day 20 (Follow-up); frequency of assessments: Day -1, Day 1, Day 7, Day 10, Day 20. Group 2: Monitored from pre-dose through Day 32 (Follow-up); frequency of assessments: Day -1, Day 1, Day 3, Day 6, Day 19, Day 22, Day 32 Group 3: Monitored from pre-dose through Day 13 (Follow-Up); frequency of assessments: Day -1, Day 1, Day 4, Day 7, Day 13 Group 4: Monitored from pre-dose through Day 13 (Follow-Up); frequency of assessments: Day -1, Day 1, Day 4, Day 7, Day 13 Group 5: Monitored from pre-dose through Day 33 (Follow-Up); frequency of assessments: D-1, Day 1, Day 3, Day 6, Day 8, Day 13, Day 18 through Day 24, Day 27, and Day 33
Secondary outcome [3] 426709 0
[Primary Outcome] To evaluate the potential effect of AR882 as a BCRP inhibitor on the plasma PK of sulfasalazine, a BCRP substrate, in healthy adult participants. Plasma PK parameters Cmax, Tmax, AUClast, AUC0-inf, t1/2 will be summarized for sulfasalazine by descriptive statistics (Group 4)
Timepoint [3] 426709 0
[Primary Timepoint] Plasma PK parameters will be assessed at the below timepoints for Group 4 Day 1: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose.
Days 2 to 3: 24, 36 and 48 hours post Day 1 dose.
Day 5: Pre-dose (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose.

Eligibility
Key inclusion criteria
* Male and/or childbearing or non-childbearing potential female participants
* Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG at the time of Screening, as deemed by the Investigator
* Body weight no less than 50 kg and body mass index (BMI) between 18 and 33 kg/m2
* Screening serum uric acid level greater than or equal to 4.5 mg/dL (268 µmol/L) and estimated glomerular filtration fate (eGFR, by Cockcroft Gault formula) greater than or equal to 90 mL/min.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Inadequate venous access or unsuitable veins for repeated venipuncture.
* Positive serology to HIV and/or hepatitis C virus , and/or hepatitis B surface antigen (HBsAg).
* History or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders that are not well controlled as per the Investigator’s judgment.
* History and/or presence of drug addiction or excessive use of alcohol within 12 months.
* Heavy caffeine drinker, > 5 servings (8-ounce/240 mL per serving) of caffeinated beverages (e.g., coffee, tea, cola, etc.) per day.

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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/10/2023
Actual
3/10/2023
Date of last participant enrolment
Anticipated
16/07/2024
Actual
16/07/2024
Date of last data collection
Anticipated
15/08/2024
Actual
16/08/2024
Sample size
Target
54
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25444 0
Nucleus Network Brisbane Clinic - Herston
Recruitment hospital [2] 26719 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 41188 0
4006 - Herston
Recruitment postcode(s) [2] 42758 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 314659 0
Commercial sector/Industry
Name [1] 314659 0
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc.
Country [1] 314659 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc
Address
58 Gipps StreetCollingwood, VIC 3066, Australia
Country
Australia
Secondary sponsor category [1] 316624 0
None
Name [1] 316624 0
Address [1] 316624 0
Country [1] 316624 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313679 0
Bellberry Limited HREC
Ethics committee address [1] 313679 0
Ethics committee country [1] 313679 0
Australia
Date submitted for ethics approval [1] 313679 0
26/07/2023
Approval date [1] 313679 0
28/08/2023
Ethics approval number [1] 313679 0

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

Contacts
Principal investigator
Name 128982 0
Dr Christopher Argent
Address 128982 0
Scientia Clinical Research Level 5 and 6, Bright Building, Corner of High and Avoca Street, Randwick NSW 2031
Country 128982 0
Australia
Phone 128982 0
+61 02 9382 5884
Fax 128982 0
Email 128982 0
[email protected]
Contact person for public queries
Name 128983 0
Elizabeth Polvent
Address 128983 0
Arthrosi Therapeutics, Inc. 9855 Towne Centre Drive,Suite 200San Diego, California 92121
Country 128983 0
United States of America
Phone 128983 0
+1 9493932676
Fax 128983 0
Email 128983 0
[email protected]
Contact person for scientific queries
Name 128984 0
Elizabeth Polvent
Address 128984 0
Arthrosi Therapeutics, Inc. 9855 Towne Centre Drive,Suite 200San Diego, California 92121
Country 128984 0
United States of America
Phone 128984 0
+1 9493932676
Fax 128984 0
Email 128984 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
Privacy and intellectual property 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.