Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of AR882 in Healthy Adult Male Volunteers
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of AR882, a Potent Uricosuric Agent, in Healthy Adult Male Volunteers
Arthrosi Therapeutics Australia Pty, Ltd a subsidiary of Arthrosi Therapeutics, Inc.
50 participants
Jun 28, 2019
Interventional
Conditions
Summary
The purpose of this study is to evaluate the safety, Tolerability Pharmacokinetics and Pharmacodynamics of AR882. There will be up to 4 cohorts with 10 subjects per cohort randomized to receive treatment with AR882 (8 subjects) or placebo (2 subjects). Dosing: Subjects will ingest IP after an overnight fast 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. Planned cohorts; Cohort 1: Subjects will be dosed (50mg) AR882 or placebo once daily for 10 days Cohort 2: Subjects will be dosed (75mg) AR882 or placebo once daily for 10 days Cohort 3: Subjects will be dosed (100mg) AR882 or placebo once daily for 10 days Cohort 4(Optional): Subjects will be dosed with a lower or intermediate dose (less than or equal to 100mg) of AR882 or placebo once daily for 10 days
Eligibility
Inclusion Criteria18
- Healthy male adult subjects greater than or equal to 18 and lesser than or equal to 55 years of age.
- Males must be surgically sterile, abstinent* or, if engaged in sexual relations with a female of child-bearing potential, the subject must agree to use 2 forms of a highly effective contraceptive methods from the time of signing the informed consent form until at least 90 days after receiving IP (AR882 or placebo).
- Abstinence is only acceptable as true abstinence as part of a preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar ovulation, symptom-thermal, post-ovulation methods), declaration of abstinences for the duration of the trial and withdrawal are not acceptable methods of contraception.
- 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).
- Able to understand the study procedures, the risks involved and willing to provide written Informed Consent before the first trial related activity.
- 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.
- All laboratory parameters (chemistry, hematology, and urinalysis) should be within normal limits or considered not clinically significant by the Investigator, in consultation with the Sponsor.
- Screening serum uric acid level greater than or equal to 4.5 mg/dL (268 micromol/L) and less than 9 mg/dL (535 micromol/L) and estimated Glomerular Filtration Rate (eGFR) greater than or equal to 90 mL/min/1.73 m².
- Subjects must be free of any clinically significant disease that requires a physician’s care and/or would interfere with study evaluations or procedures.
- Normal or clinically acceptable physical examination.
- No clinically relevant abnormalities in twelve-lead electrocardiogram as per Investigator judgment.
- No clinically relevant abnormalities in blood pressure (BP), heart rate (HR), body temperature and respiratory rate as per the Investigator’s judgment, see normal values for information:
- a. 90 mm Hg lesser than or equal to systolic BP lesser than or equal to 140 mmHg in supine position.
- b. 40 mm Hg lesser than or equal to diastolic BP lesser than or equal to 90 mm Hg in supine position.
- c. 40 bpm lesser than or equal to heart rate lesser than or equal to 100 bpm in supine position.
- d. 35.5 °C lesser than or equal to body temperature lesser than or equal to 37.5 °C.
- e. 10 bpm lesser than or equal to respiratory rate lesser than or equal to 22 bpm.
Exclusion Criteria64
- 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).
- History of cardiac abnormalities including abnormal and clinically relevant ECG
- changes such as bradycardia (sinus rate < 40 bpm), complete LBBB, RBBB,
- incomplete LBBB, second or third degree heart block, intraventricular conduction
- delay with QRS duration > 120 msec, symptomatic or asymptomatic arrhythmias
- with the exception of sinus arrhythmia, evidence of ventricular pre-excitation,
- frequent palpitations or syncopal episodes, heart failure, hypokalemia, family
- history of Long QT Syndrome, family history of sudden death in otherwise
- healthy individual between the ages of 1 and 30 years.
- Conditions predisposing to QT prolongation including pathological Q-wave
- (defined as Q-wave >40 msec or depth > 0.4-0.5 mV).
- Any use of concomitant medications that prolong the QT/QTc interval within
- days prior to Day 1.
- Subjects with a QTcF interval (QT interval corrected for heart rate according to
- Fridericia) > 450 milliseconds (ms) at Screening or on Day –1 or at pre-dose on
- Day 1.
- Subjects who have undergone major surgery within 3 months of Day 1.
- Subjects who previously received AR882 or an investigational product, biological
- agent, or device within 3 months or 5 half-lives of the investigational agent,
- whichever is longer.
- Subjects who donated blood within 12 weeks prior to Day 1 or who have given a
- plasma donation within 4 weeks prior to the screening visit.
- Any drug treatment, including prescribed or OTC medicines or herbal
- preparations, taken in the 14 days (2 months for enzyme-inducing drugs or
- products e.g., glucocorticoids, phenobarbital, isoniazid, St. John’s Wort)
- preceding the dosing of IP.
- Use of tobacco products within 30 days prior to dosing.
- Heavy caffeine drinker (> 5 cups or glasses of caffeinated beverages e.g., coffee,
- tea, cola per day).
- Subjects who refuse to abstain from alcohol, or caffeine containing foods or
- beverages, or grapefruit containing foods or beverages, or Seville orange
- containing foods or beverages, or fruit juice, or sweetened soft drinks from 48
- hours prior to dosing and for the entire duration of the study.
- History and/or presence of drug addiction or excessive use of alcohol within 6
- months prior to Screening defined as > 14 drinks/week (1 drink = 5 ounces
- (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard
- liquor).
- Subjects who have a positive alcohol test (breath or urine test) at Screening or at
- Day -2 (Admission).
- Subjects who have a positive test for drugs of abuse (cocaine,
- tetrahydrocannabinol, methamphetamine, amphetamine, benzodiazepines,
- methadone, barbiturates, amphetamine, opiates, methylenedioxy
- methamphetamine, phencyclidine) or cotinine (metabolite of nicotine) at
- Screening or at Day -2 (Admission).
- Subjects who refuse to refrain from strenuous exercise within 48 hours of dose
- administration through study completion.
- Subjects who have a clinically relevant intolerance or allergy to foods or drugs or
- are known or suspected to have hypersensitivity to benzbromarone and/or any
- ingredient in the investigational products.
- Subjects in a situation or with a condition that, in the opinion of the Investigator,
- may interfere with optimal participation in the study.
- Subjects unable to comply with study restrictions.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
This study will be conducted at a single center. There will be up to 4 cohorts with 10 subjects per cohort. Subjects in each cohort will be randomized to receive treatment with AR882 (8 subjects) or placebo (2 subjects). Cohorts 1 to 4 will enroll sequentially following review of safety and PK data of prior cohorts by the Investigator and Sponsor Medical Monitor. Dosing: Subjects will 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. Starting dose of IP will be 50mg. Planned cohorts; Cohort 1: (50mg) AR882 or placebo once daily for 10 days Cohort 2: (75mg) AR882 or placebo once daily for 10 days Cohort 3: (100mg) AR882 or placebo once daily for 10 days Cohort 4 (less than or equal to 100mg): Subjects will be dosed with a lower or intermediate dose of AR882 or placebo once daily for 10 days. Decision to proceed with Cohort 4 will be based on preliminary review of previous cohorts’ PK/PD and Safety/tolerability data. Strategies used to monitor adherence to the intervention: Laboratory tests and pharmacokinetic analyses. Strategies used to ensure compliance with the fasts: Inpatient stay and observation
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12619000908134