Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000021178
Ethics application status
Approved
Date submitted
20/12/2018
Date registered
9/01/2019
Date last updated
13/08/2019
Date data sharing statement initially provided
9/01/2019
Date results information initially provided
13/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Rising Dose Study of AR882 in Healthy Adult Male Volunteers
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Rising Dose Study of AR882, a Potent Uricosuric Agent, in Healthy Adult Male Volunteers
Secondary ID [1] 296838 0
AR882-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic gout 310747 0
Hyperuricemia 310902 0
Condition category
Condition code
Musculoskeletal 309439 309439 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 309635 309635 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted in two parts. There will be up to 9 cohorts with 8 subjects per cohort. Part 1 will evaluate single ascending doses of AR882 and Part 2 consists of cohorts to evaluate the pharmacokinetics of AR882 under various conditions.
Part 1 (Cohorts 1 to 5): Subjects in each cohort will be randomized to receive treatment with AR882 or placebo. Subjects randomised to Cohort 1-5 will ingest an oral suspension of AR882 of Dose A, Dose B, Dose C, Dose D and Dose E respectively after an overnight fast of at least 10 hours and will remain fasted until at least 4 hours post-dose.
Part 2 will include Cohorts 6 to 9. Cohort 6 is a stand-alone, fed-state cohort. Subjects randomised to Cohort 6 will ingest the oral suspension of AR882 (Dose B) approximately 30 minutes after subjects begin to consume a high-fat, high-calorie breakfast. Food is provided to participants at site. Subjects randomised to Cohort 7 will ingest the oral capsule of AR882 (Dose B) after an overnight fast (Food only, water is allowed during the period of fasting ad libitum) of at least 10 hours and subjects will remain fasted until at least 4 hours post-dose.
Cohorts 8 and 9 are combination arms including Allopurinol 300mg/AR882 (Dose B) and Febuxostat 40mg/AR882 (Dose B) respectively. In combination arm, sequence of ingestion will be AR882 immediately followed by Allopurinol or Febuxostat.
Sequence A: Allopurinol or Febuxostat on Day 1; AR882 and allopurinol 300 mg or Febuxostat on Day 8
Sequence B: AR882 and allopurinol or Febuxostat on Day 1;allopurinol or Febuxostat alone on Day 8.

The specification of dosages are listed below:
Dose A= 15mg
Dose B= 50mg
Dose C= 100mg
Dose D= 150mg
Dose E= 200mg
Intervention code [1] 313122 0
Treatment: Drugs
Comparator / control treatment
Matching Placebo (Suspending vehicle- Cohort 1-6 and Solid oral placebo capsule- Cohort 7).
• Ora-Sweet Sugar free composition:
Ingredients
Purified water, glycerin, sorbitol, sodium saccharin, xanthan gum, and flavoring. Buffered with citric acid and sodium citrate. Preserved with methylparaben (0.03%), potassium sorbate (0.1%), and propylparaben (0.008%).
Specifications
Appearance: Clear liquid with a slight tint
pH range: 4.0 - 4.4
Taste: Sweet citrus-berry flavor
Osmolality: Approximately 1979 mOsm/kg

• Ora-Plus composition:
Ingredients
Purified water, microcrystalline cellulose, carboxymethylcellulose sodium, xanthan gum, carrageenan, calcium sulfate, trisodium phosphate, citric acid and sodium phosphate as buffers, dimethicone antifoam emulsion. Preserved with methylparaben and potassium sorbate.
Specifications
Appearance: Translucent, milky white, thixotropic liquid
pH range: 4.0 - 4.5
Taste: Very bland taste (no sweeteners or flavors)
Viscosity: Thixotropic. Range 1300 - 6700 cps at 25ºC via Brookfield viscometer
Osmolality: Approximately 157 mOsm/kg

• Placebo AR882 capsule composition : HPMC (Hydroxy Propyl Methyl Cellulose) capsule shell matched to IP, which contains the same excipients as the AR882.
Control group
Placebo

Outcomes
Primary outcome [1] 308412 0
To evaluate the safety profile of the AR882 when administered as rising single oral doses of an oral formulation.
Outcome is assessed: Serum assay, Urine assay, Physical examination
Timepoint [1] 308412 0
Cohort 1 to 7: Monitored during screening and daily through Day -2, Day -1, day 1, day 2, Day 3, Day 4, Day 5, Day 6, Day 8 (Follow Up) after the last dose of the study treatment.
Cohort 8 and 9: Monitored during screening, Day -2, Day 2, Day 4, Day 6, Day 9, Day 11, Day 15
Primary outcome [2] 308413 0
To evaluate the single-dose pharmacokinetics (PK) of AR882 after oral administration of an oral formulation. Plasma parameters Cmax, Tmax, AUClast, AUCinf, lambda z, and t1/2, and urinary parameters Ae and CLr will be evaluated.
Timepoint [2] 308413 0
Plasma samples will be collected at the following time-points in relation to dosing on: pre-dose (within 30 minutes before dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, 48, 54, 60, 72, 96, and 120 hours post-dose. Urine (total catch) will be collected over the following intervals in relation to dosing on Day 1: -24 to -18, -18 to -12, -12 to 0, 0 to 6, 6 to 12, 12 to 24, 24 to 30, 30 to 36, 36 to 48, 48 to 54, 54 to 60, and 60 to 72 hours post-dose.
Secondary outcome [1] 354893 0
To evaluate the single-dose pharmacodynamic (PD) effects (sUA lowering) of AR882 after oral administration of an oral formulation.
Timepoint [1] 354893 0
PD parameters will be assessed from pre-dose till 120 hours in relation to dosing.
Frequency will include 6-hour, 12-hour and 24-hour intervals from Day -1 to Day 6 (Cohorts 1-7) and Day-1 to Day 13 (Cohorts 8-9).

Eligibility
Key inclusion criteria
1. Healthy male adult subjects greater than or equal to 18 and lesser than or equal to 55 years of age.
2. Male subjects must be surgically sterile or, if engaged in sexual relations with a female of child-bearing potential, must agree to use contraception as described in the protocol.
3. Males must agree to refrain from sperm donation from the time of signing the informed consent form until at least 90 days after receiving IP (AR882 or placebo).
4. Body weight no less than 50 kg and body mass index (BMI) within the range of greater than or equal to 18 and lesser than or equal to 33 kg/m2.
5. Screening serum uric acid level greater than or equal to 4.5 mg/dL (268 µmol/L).
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Inadequate venous access or unsuitable veins for repeated venipuncture.
2. Any concomitant chronic or acute illness or an acute febrile illness within 1 week of dose administration.
3. Positive serology to HIV (HIV1 and HIV2) and/or Hepatitis C antibodies (HCV), and/or Hepatitis B surface antigen (HBsAg).
4. History or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders.
5. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been successfully treated. Healthy volunteers with a history of other malignancies that have been treated with curative intent and which have no recurrence within 5 years may also be eligible if approved by the Sponsor Medical Monitor (or designee).
6. Subjects who have undergone major surgery within 3 months of Day 1.
7. Use of tobacco products within 30 days prior to dosing.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/01/2019
Actual
15/01/2019
Date of last participant enrolment
Anticipated
30/06/2019
Actual
17/07/2019
Date of last data collection
Anticipated
30/07/2019
Actual
31/07/2019
Sample size
Target
72
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12762 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 25191 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 301413 0
Commercial sector/Industry
Name [1] 301413 0
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc.
Country [1] 301413 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc.
Address
58 Gipps Street
Collingwood, VIC 3066, Australia
Country
Australia
Secondary sponsor category [1] 301089 0
None
Name [1] 301089 0
Address [1] 301089 0
Country [1] 301089 0
Other collaborator category [1] 280469 0
Commercial sector/Industry
Name [1] 280469 0
Novotech (Australia) Pty Limited
Address [1] 280469 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280469 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302147 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 302147 0
55 Commercial road, Melbourne , Vic - 3004
Ethics committee country [1] 302147 0
Australia
Date submitted for ethics approval [1] 302147 0
21/11/2018
Approval date [1] 302147 0
19/12/2018
Ethics approval number [1] 302147 0

Summary
Brief summary
The purpose of this study is to evaluate the safety, Pharmacokinetics and Pharmacodynamics of AR882. This study will be conducted in two parts. There will be up to 9 cohorts with 8 subjects per cohort. Part 1 will evaluate single ascending doses of AR882 and Part 2 consists of cohorts to evaluate the pharmacokinetics of AR882 under various conditions.
Part 1 (Cohorts 1 to 5): Subjects in each cohort will be randomized to receive treatment with AR882 or placebo. Subjects randomised to Cohort 1-5 will ingest an oral suspension of AR882 of Dose A, Dose B, Dose C, Dose D and Dose E respectively after an overnight fast of at least 10 hours and will remain fasted until at least 4 hours post-dose.
Part 2 will include Cohorts 6 to 9. Cohort 6 is a stand-alone, fed-state cohort. Subjects randomised to Cohort 6 will ingest the oral suspension of AR882 (Dose B) approximately 30 minutes after subjects begin to consume a high-fat, high-calorie breakfast. Subjects randomised to Cohort 7 will ingest the oral capsule of AR882 (Dose B) after an overnight fast of at least 10 hours and subjects will remain fasted until at least 4 hours post-dose.
In Cohort 8 and 9 , Subjects will ingest allopurinol/Febuxostat after an overnight fast of at least 10 hours and will remain fasted until at least 4 hours post dose. In the AR882 combination treatment, subjects will ingest AR882 first immediately followed by ingestion of Allopurinol/Febuxostat.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89282 0
Dr Jason Lickliter
Address 89282 0
Nucleus Network Pty Ltd. Address: Level 5, Burnet Tower, AMREP Precinct, 89 Commercial Road Melbourne, VIC 3004
Country 89282 0
Australia
Phone 89282 0
+61 3 9076 8960
Fax 89282 0
Email 89282 0
[email protected]
Contact person for public queries
Name 89283 0
Miss Arti Patel
Address 89283 0
Novotech Australia Pty Ltd
PO Box 244 PYRMONT NSW 2009, Australia
Country 89283 0
Australia
Phone 89283 0
+61 3 9341 1910
Fax 89283 0
Email 89283 0
[email protected]
Contact person for scientific queries
Name 89284 0
Miss Arti Patel
Address 89284 0
Novotech Australia Pty Ltd
PO Box 244 PYRMONT NSW 2009, Australia
Country 89284 0
Australia
Phone 89284 0
+61 3 9341 1910
Fax 89284 0
Email 89284 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

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