Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000642482
Ethics application status
Approved
Date submitted
10/05/2016
Date registered
18/05/2016
Date last updated
20/09/2016
Type of registration
Prospectively registered

Titles & IDs
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.
Secondary ID [1] 289105 0
Protocol Number: RVX222-CS-016
Universal Trial Number (UTN)
U1111-1182-3664
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe renal impairment. 298564 0
Condition category
Condition code
Renal and Urogenital 298646 298646 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 294608 0
Treatment: Drugs
Comparator / control treatment
Eight (8) healthy control subjects, age-, gender- and weight- matched to eight (8) End Stage Renal Disease (ESRD) subjects.
Control group
Active

Outcomes
Primary outcome [1] 298141 0
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.
Timepoint [1] 298141 0
- 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.
Primary outcome [2] 298274 0
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.
Timepoint [2] 298274 0
- 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.
Secondary outcome [1] 323261 0
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).
Timepoint [1] 323261 0
Blood samples for measurement of biomarkers in plasma would be collected on Day 1, Day 2 and Day 3.

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2016
Actual
19/07/2016
Date of last participant enrolment
Anticipated
2/09/2016
Actual
10/09/2016
Date of last data collection
Anticipated
16/09/2016
Actual
16/09/2016
Sample size
Target
16
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 7846 0
New Zealand
State/province [1] 7846 0
Christchurch

Funding & Sponsors
Funding source category [1] 293491 0
Commercial sector/Industry
Name [1] 293491 0
Resverlogix Corp
Country [1] 293491 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
CPR Pharma Services Pty Ltd
Address
c/o Infinity Consulting Ltd
PO Box 105 239
Auckland City 1143
Country
New Zealand
Secondary sponsor category [1] 292315 0
Commercial sector/Industry
Name [1] 292315 0
Resverlogix Corp
Address [1] 292315 0
300, 4820 Richard Road SW
Calgary, AB, T3E 6L1
Country [1] 292315 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294934 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 294934 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Thorndon
Wellington 6011
Ethics committee country [1] 294934 0
New Zealand
Date submitted for ethics approval [1] 294934 0
04/05/2016
Approval date [1] 294934 0
24/05/2016
Ethics approval number [1] 294934 0

Summary
Brief summary
RVX000222 is being developed to prevent major heart events in individuals at high risk of heart disease.
RVX000222 is mainly cleared from the body by the liver, with only a small amount of each dose cleared by the kidneys. The study team wants to confirm this by comparing how RVX000222 is processed and cleared by the body,in adults with severely reduced kidney function and in adults whose kidneys are working normally. The study will also collect information about how safe and well toleratedRVX000222 is.
Two groups will be enrolled for the study:
Group 1: approximately 8 adults with severely reduced kidney function, and
Group 2: approximately 8 adults with normal kidney function.
Each participant in Group 2 will be selected as a 'match' for a Group 1 participant, based on age, weight, and gender.
Every person in the study will take a single 100 mg dose of RVX000222, by mouth, on Day 1 of the study only.
Levels of the study drug and its breakdown products will be measured in blood and urine samples collected at specific times after dosing, and any changes in health will be recorded.
The results will provide important information about whether the dose of RVX000222 needs to be adjusted when used by patients with reduced kidney function.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65478 0
Dr Richard Robson
Address 65478 0
Christchurch Clinical Studies Trust Ltd (CCST)
PO Box 2856
Christchurch 8140
Country 65478 0
New Zealand
Phone 65478 0
+64 3 372 9477
Fax 65478 0
Email 65478 0
richard@ccst.co.nz
Contact person for public queries
Name 65479 0
Dr Devonie Waaka
Address 65479 0
Christchurch Clinical Studies Trust Ltd (CCST)
PO Box 2856
Christchurch 8140
Country 65479 0
New Zealand
Phone 65479 0
+64 3 372 9477
Fax 65479 0
Email 65479 0
devonie@ccst.co.nz
Contact person for scientific queries
Name 65480 0
Dr Michael Sweeney
Address 65480 0
Resverlogix Corp.
300, 4820 Richard Road SW
Calgary, AB, T3E 6L1
Country 65480 0
Canada
Phone 65480 0
+1 415 470 5613
Fax 65480 0
Email 65480 0
clinicaltrials@resverlogix.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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