Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients

End-stage Renal Disease Clinical Trial

— DARE-ESKD 1  

Official title:

Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients: on Behalf of the DARE-ESKD Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05343078
• Other study ID #: 50393421.4.0000.5404
• Status: Completed
• Phase: Phase 4
• Start date: April 25, 2022
• Est. completion date: October 1, 2022

Study information

• Verified date: March 2023
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sodium-glucose co-transporter 2 inhibitors (Sglt2i) attenuate the incidence of cardiovascular events in individuals with preserved or mildly reduced kidney function. Whether this benefit is also observed among individuals with end-stage renal disease (ESRD), in whom cardiovascular disease is a leading cause of mortality, remains unexplored. To appraise the influence of dialysis on the pharmacokinetics of Sglt2i is a prerequisite to determining the treatment regimen that best fits this population.

In this study ESRD individuals, aged 18 years and older, on a regular dialysis regimen for a minimum of 3 months at the Nephrology Division of the Clinics Hospital of the University of Campinas (Unicamp) will be enrolled in a pharmacokinetics study.

In the single-dose protocol, hemodialysis participants will take Dapagliflozin 10mg P.O. immediately before the dialysis session, and blood samples will be collected every 30min during dialysis and again 24h and 48h after termination. The dialysate will be continuously sampled in a tank and aliquots collected for further analysis.

In the multiple-dose protocol, both hemodialysis and peritoneal dialysis participants will take Dapagliflozin 10mg P.O. daily in the morning for 7 days. Blood samples will be collected at baseline, and again after 48h and 7 days.

The plasma levels of dapagliflozin and its inactive metabolite, D3OG, will be calculated from blood and dialysate samples using liquid chromatography mass spectrometry.

The primary outcome is the plasma concentration-time curve of dapagliflozin and its inactive metabolite D3OG during a regular hemodialysis session. Secondary outcomes are: (i) the steady-state plasma concentration of Dapa; (ii) the accumulation ratio of Dapa; (iii) the total mass of Dapa and D3OG extracted by the dialysate; (iv) the dialytic clearance of dapagliflozin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: October 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Dialysis for 3 months or more prior to enrollment

• 18 years of age or older

• Signed the informed consent form

Exclusion Criteria:

• Liver dysfunction

• Allergy to dapagliflozin

• Currently receiving a Sglt2i

Related Conditions & MeSH terms

• End-stage Renal Disease
• Kidney Failure, Chronic

Intervention

Drug:
• Dapagliflozin 10Mg Tab
Participants will take a single-dose Dapagliflozin 10mg P.O. prior to the hemodialysis session for the single-dose pharmacokinetics protocol. In the multiple-dose protocol, Dapagliflozin 10mg P.O. will be taken daily in the morning for one week.

Locations

Country	Name	City	State
Brazil	University of Campinas	Campinas	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Campinas, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve of the plasma concentration-time curve of dapagliflozin	AUC of dapagliflozin (ng.mL / mL)	From dialysis initiation to 48 hours post- drug administration
Secondary	Area under the curve of the plasma concentration-time curve of D3OG	AUC of D3OG (ng.mL / mL)	From dialysis initiation to 48 hours post- drug administration
Secondary	Steady-state plasma concentration of Dapagliflozin	Steady-state plasma concentration (ng/mL)	7 days
Secondary	Steady-state accumulation ratio of Dapagliflozin	Accumulation index	7 days
Secondary	Total mass of dapagliflozin extracted by the dialysis	Dapagliflozin mass (mg)	7 days