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.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12616000642482
• Date of registration: 18/05/2016
• Prospective Registration: Yes
• Primary sponsor: CPR Pharma Services Pty Ltd
• Public title: 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.
• Scientific title: A Phase I, Open-Label, Parallel Group Study to Evaluate the Safety and Pharmacokinetics of a Single Oral Dose of RVX000222 in Subjects with Severe Renal Impairment.
• Date of first enrolment: 19/07/2016
• Target sample size: 16
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12616000642482.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Pharmacokinetics;
• Phase: Phase 1

Countries of recruitment

New Zealand

Contacts

• Name: Dr Devonie Waaka

• Name: Dr Michael Sweeney

Key inclusion & exclusion criteria

Inclusion criteria: 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).
Exclusion criteria: 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.

Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Renal and Urogenital - Kidney disease

Severe renal impairment.;
Severe renal impairment.

Intervention(s)

This will be an open-label, parallel group clinical study to evaluate the safety and Pharmacokinetics of a single 100 mg oral dose of RVX000222 in subjects with renal impairment and age-, weight-, and gender- matched healthy subjects.

Two Cohorts of eight (8) subjects will be enrolled in the study:
- Cohort 1: approximately eight (8) subjects with severe renal impairment, and
- Cohort 2: approximately eight (8) healthy control subjects.
Each participant in Cohort 2 will be selected as a 'match' for a Cohort 1 participant, based on age, weight, and gender.

Each participant in the study will receive a single oral administration of the study drug, RVX000222 100mg capsule.

Primary Outcome(s)

To assess the pharmacokinetics (PK) of single oral administration of RVX000222 in subjects with severe renal impairment.
Method of assessment: PK blood and urine sampling.[- PK blood samples would be collected at Day 1, Day 2, Day 3 and Day 7.
- PK urine samples would be collected at Day 1, Day 2 and Day 3.]

To assess the safety and tolerability of single oral administration of RVX000222 in subjects with severe renal impairment.
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.
- Physical examination would be at Screening, Day -1, Day 3 and Day 7.
- 12-lead Electrocardiograms (ECG) would be at Screening and Day 7.
- Clinical laboratory tests would be collected at Screening, Day -1, Day 2, Day 3 and Day 7.
- All Adverse Events will be collected from Screening to Day 7.]

Secondary Outcome(s)

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.]

Secondary ID(s)

Protocol Number: RVX222-CS-016

Source(s) of Monetary Support

Resverlogix Corp

Secondary Sponsor(s)

Resverlogix Corp

Ethics review

Status: Approved
Approval date:
Contact:

Southern Health and Disability Ethics Committee