A study comparing how fast the trial drug RVX000222 is cleared from the body, in healthy adults and in adults with severely reduced kidney function.
- Conditions
- Severe renal impairment.Renal and Urogenital - Kidney disease
- Registration Number
- ACTRN12616000642482
- Lead Sponsor
- CPR Pharma Services Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 16
1. Male or female between 18 and 80 years old, inclusive;
2. If female, have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1, or meet at least one of the following criteria: post-surgical sterilization or two years postmenopausal.
3. If subject is female of childbearing potential, subject must be willing to practice an acceptable non-hormonal method of birth control from Day 1 through until at least 30 days post study drug administration (e.g., abstinence);
4. Provide written informed consent before participation in the study;
5. Stable renal function, in the opinion of the Investigator, for at least 3 months prior to Screen visit.
Cohort 1: Renal Impairment Subjects:
6. Previously diagnosed with ESRD and not on dialysis (eGFR <30 mL/min/1.73m2).
Cohort 2: Healthy Subjects:
7. Healthy volunteers matched for age (plus or minus 10 years), weight (plus or minus 20%), and gender with the subjects in Cohort 1 (renal impaired subjects);
8. eGFR greater than or equal to 60 mL/min/1.73m2).
1. Currently undergoing renal dialysis;
2. Have donated blood or plasma, in excess of 500 mL. during the 30-day period before Day -1;
3. History of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin;
4. Evidence of cirrhosis from liver imaging or biopsy, history of hepatic encephalopathy, esophageal or gastric varices, active hepatitis, or prior porta-caval shunt procedure, or a Child-Pugh score of at least 5 points;
5. Have active cholecystitis or gallbladder symptoms within 60 days before Day -1 (subjects who have had a cholecystectomy are not excluded from this study);
6. Type 2 diabetes mellitus with unstable disease or changes in therapy (30) days prior to Day -1 (clinical trial unit admission) may be excluded, as determined by the investigator and/or medical monitor;
7. Have a screening 12-lead ECG considered clinically significant by the investigator;
8. Body Mass Index (BMI) >40 kg/m2;
9. Have positive test results for, or evidence of active infection with human immunodeficiency virus type 1 or 2, hepatitis A, B, or C;
10. Hormonal contraceptives are not allowed during study participation by study subjects from Visit 1/Screen until 48 hours post study drug administration. Subjects who take hormone replacement therapy must be willing to discontinue their hormonal therapy if it is medically appropriate;
11. Current or recent (within 12 months prior to Screen) use of systemic immunosuppressants, including but not limited to, corticosteroids (prednisone equivalent of >20 mg/day for >2 weeks), azathioprine, or cyclosporine;
12. Use of strong inhibitors or inducers of CYP3A4/5, OATP1B1, and OAT1/3 within 30 days of five half-lives, whichever is longer, prior to Day -1 (clinical research unit admission) and during the study (e.g. Boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazone, opinvir/rionavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinarir, telaprevir, telithromycin, voriconazole, rifampin, carbamazepine, phenytoin, or probenecid);
13. Use of diclofenac or clavulanic acid from 7 days prior to Day 1 (treatment day) and during the study;
14. Use of >1.0g acetaminophen from Day -1 (clinical research unit admission) to Day 1 (treatment day);
15. Have consumed grapefruit juice within 7 days before Day -1 to 48 hours post study drug administration;
16. Have any known allergy or intolerance to any compound in RVX000222 or any other closely related compound;
17. Are unwilling to abstain from alcoholic beverages, caffeine or xanthine-containing products, and use of nicotine products during the clinical research unit confinement period;
18. Have a positive result on drugs of abuse screen testing (Screen and Day -1). If a subject tests positive for a drug of abuse, and has a current prescription for the drug to treat a defined indication, the subject may be eligible for the participation;
19. Alanine transaminase (ALT) or Aspartate transaminase (AST) >2.0 x upper limit of normal (ULN) at Screen;
20. Total bilirubin >1.5 x upper limit of normal at Screen;
21. Have participated in a clinical study and received any investigational medication within the last 30 days or five half-lives, whichever is long, preceding Day -1;
22. In the opinion of the investigator, are not able or willing to comply with the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the safety and tolerability of single oral administration of RVX000222 in subjects with severe renal impairment.<br>Method of assessment: vital signs, physical examination, 12-lead electrocardiograms (ECG), clinical laboratory tests and adverse events.[- Vital signs would be at Screening, Day -1, Day 1 , Day 2, Day 3 and Day 7.<br>- Physical examination would be at Screening, Day -1, Day 3 and Day 7.<br>- 12-lead Electrocardiograms (ECG) would be at Screening and Day 7.<br>- Clinical laboratory tests would be collected at Screening, Day -1, Day 2, Day 3 and Day 7.<br>- All Adverse Events will be collected from Screening to Day 7.];To assess the pharmacokinetics (PK) of single oral administration of RVX000222 in subjects with severe renal impairment.<br>Method of assessment: PK blood and urine sampling.[- PK blood samples would be collected at Day 1, Day 2, Day 3 and Day 7.<br>- PK urine samples would be collected at Day 1, Day 2 and Day 3.]
- Secondary Outcome Measures
Name Time Method The exploratory objective of the study is to evaluate acute changes in biomarker relevant to Bromodomain Extra Terminal (BET) inhibition. A proteomic analysis involving 1300 protein markers will be conducted. The analysis will be conducted using the SOMAscan assay and reagents offered by SomaLogic (http://www.somalogic.com/About-Us.aspx).[Blood samples for measurement of biomarkers in plasma would be collected on Day 1, Day 2 and Day 3.]