Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001371785
Ethics application status
Approved
Date submitted
8/08/2022
Date registered
26/10/2022
Date last updated
3/03/2023
Date data sharing statement initially provided
26/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Empagliflozin in stage 4 non-diabetic kidney disease
Scientific title
Sodium glucose co-transporter 2 inhibitors (SGLT2-I) effect on glucose and sodium clearance in those with stage 4 non-diabetic chronic kidney disease.
Secondary ID [1] 307731 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic kidney disease 327298 0
Condition category
Condition code
Renal and Urogenital 324435 324435 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
empagliflozin 10mg tablet orally daily for 7 days, then increased to 25mg orally daily for 7 days followed by a 7 day wash out phase.
The wash out phase is to observe how quickly kidney function returns to baseline following cessation of the drug.
Participants will bring in drug container at end of each 7 day period to check complicance.
Intervention code [1] 324204 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332243 0
Empagliflozin pharmacokinetics will be characterised using standard non-compartmental methods as well as a non-linear mixed effects methodology. Pharmacokinetic parameters including maximum and minimal plasma concentrations, volume of distribution, half-life, area-under the plasma concentration time curve (for the 24 hour profile), total apparent plasma clearance, free ad bound clearance, and renal clearance will be estimated as well as measured using urinary excretion and compared to those expected for individuals with CKD3 and 2.
Timepoint [1] 332243 0
Samples will be taken at 0, 20 minutes, 40-minute, 1 hour, 2 hour, 4 hours, 6 hours, 8 hours and 24 hours post dose on day 1 of treatment. Timed urine collection will be at 0-4 hours, 4-8 hours and 8 - 24 hours.
Then samples at 12 hours post dose will be taken on days 4,6,7,,8, 11,13,14 post treatment, and day 21 - 7 days after wash out.
These parameters will be used to determine pharmacokinetics and pharmacodynamics of empagliflozin in CKD stage 4.
Secondary outcome [1] 412681 0
changes in urinary sodium excretion.
Timepoint [1] 412681 0
at 24 hours, 7 days, day 8, and day 14 post treatment commencement.
Secondary outcome [2] 413325 0
changes in urinary glucose excretion.
Timepoint [2] 413325 0
at 24 hours, day 7 and day 14 post treatment commencement.
Secondary outcome [3] 413326 0
changes in urinary uric acid excretion
Timepoint [3] 413326 0
at 24 hours, day 7 and day 14 post treatment commencement.
Secondary outcome [4] 415077 0
changes in Blood pressure as a marker of cardiac function, measured using sphygmomanometer - average of 3 recording over 15 minutes in a seated position.
Timepoint [4] 415077 0
at 24 hours, day 7 and day 14 post treatment commencement.

Eligibility
Key inclusion criteria
Now expanded to Individuals with non-diabetic stage 4 kidney disease with a stable eGFR between 30 and 15 ml/min/1.73m2 for the past 3 months.
No change in medications over past 3 months.
Not previously on empagliflozin.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
.
Not able to give informed consent.

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 3 / Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Analysis plan: Pharmacokinetic data will be used to undertake modelling, using a population pharmacokinetic approach with the standard software NONMEM (ver 7.2.0).
Previous pharmacokinetic studies in CKD have used the same numbers to achieve a valid result.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/11/2022
Actual
12/01/2023
Date of last participant enrolment
Anticipated
30/11/2023
Actual
Date of last data collection
Anticipated
21/12/2023
Actual
Sample size
Target
6
Accrual to date
1
Final
Recruitment outside Australia
Country [1] 24937 0
New Zealand
State/province [1] 24937 0
Otago

Funding & Sponsors
Funding source category [1] 312002 0
Charities/Societies/Foundations
Name [1] 312002 0
Otago Medical Research Foundation
Country [1] 312002 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Department of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 313497 0
None
Name [1] 313497 0
Address [1] 313497 0
Country [1] 313497 0
Other collaborator category [1] 282399 0
Individual
Name [1] 282399 0
Dr Luke Wilson
Address [1] 282399 0
Department of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country [1] 282399 0
New Zealand
Other collaborator category [2] 282400 0
Individual
Name [2] 282400 0
Dr John Schollum
Address [2] 282400 0
Department of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country [2] 282400 0
New Zealand
Other collaborator category [3] 282401 0
Individual
Name [3] 282401 0
Dr Tracey Putt
Address [3] 282401 0
Department of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country [3] 282401 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311424 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 311424 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 311424 0
New Zealand
Date submitted for ethics approval [1] 311424 0
04/08/2022
Approval date [1] 311424 0
21/10/2022
Ethics approval number [1] 311424 0
2022 FULL 12970

Summary
Brief summary
This pilot study aims to have a better understanding of the pharmacokinetics and pharmacodynamics of two oral doses of empagliflozin and the drug's effect on glucose and sodium clearance as well as kidney function, blood pressure and cardiac function as assessed by echocardiography in those with among Stage 4 non diabetic chronic kidney disease (CKD).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121046 0
Prof Robert Walker
Address 121046 0
Department of Medicine
University of Otago
PO Box 56 Dunedin 9054
Country 121046 0
New Zealand
Phone 121046 0
+64 274359552
Fax 121046 0
Email 121046 0
rob.walker@otago.ac.nz
Contact person for public queries
Name 121047 0
Prof Robert Walker
Address 121047 0
Department of Medicine
University of Otago
PO Box 56 Dunedin 9054
Country 121047 0
New Zealand
Phone 121047 0
+64 274359552
Fax 121047 0
Email 121047 0
rob.walker@otago.ac.nz
Contact person for scientific queries
Name 121048 0
Prof Robert Walker
Address 121048 0
Department of Medicine
University of Otago
PO Box 56 Dunedin 9054
Country 121048 0
New Zealand
Phone 121048 0
+64 274359552
Fax 121048 0
Email 121048 0
rob.walker@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
de-identified pharmacokinetic data for each participant along with urinary sodium, glucose and uric acid clearances will be made available with appropriate ethics approval.
When will data be available (start and end dates)?
Once analysis is complete - expected 1st December 2023. Available for 5 years after completion of analyses.
Available to whom?
Suitably qualified researchers from recognised academic institutions.
Available for what types of analyses?
Pharmacokinetic analyses.
How or where can data be obtained?
Through contact with the primary investigator.
rob.walker@otago.ac.nz


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16860Study protocol  rob.walker@otago.ac.nz From PI
16861Informed consent form  rob.walker@otago.ac.nz 384497-(Uploaded-24-10-2022-18-59-09)-Study-related document.docx
16862Ethical approval  rob.walker@otago.ac.nz 384497-(Uploaded-24-10-2022-12-57-07)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.