Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Rising Dose Study of AR882 in Healthy Adult Male Volunteers
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Rising Dose Study of AR882, a Potent Uricosuric Agent, in Healthy Adult Male Volunteers
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc.
72 participants
Jan 15, 2019
Interventional
Conditions
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.
Eligibility
Inclusion Criteria5
- Healthy male adult subjects greater than or equal to 18 and lesser than or equal to 55 years of age.
- 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.
- 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).
- 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.
- Screening serum uric acid level greater than or equal to 4.5 mg/dL (268 µmol/L).
Exclusion Criteria7
- Inadequate venous access or unsuitable veins for repeated venipuncture.
- Any concomitant chronic or acute illness or an acute febrile illness within 1 week of dose administration.
- Positive serology to HIV (HIV1 and HIV2) and/or Hepatitis C antibodies (HCV), 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.
- 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).
- Subjects who have undergone major surgery within 3 months of Day 1.
- Use of tobacco products within 30 days prior to dosing.
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Interventions
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
Locations(1)
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ACTRN12619000021178