Clinical trial NCT05343078: Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients
Official title: Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients: on Behalf of the DARE-ESKD Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Disease
Keywords: hemodialysis
dapagliflozin
peritoneal dialysis
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2022-04-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: In the single-dose protocol, hemodialysis participants will take the experimental drug immediately prior to the dialysis session. In the multiple-dose protocol, volunteers will take the drug daily in the morning for one week.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the curve of the plasma concentration-time curve of dapagliflozin
timeFrame: From dialysis initiation to 48 hours post- drug administration
Secondary outcomes:
measure: Area under the curve of the plasma concentration-time curve of D3OG
timeFrame: From dialysis initiation to 48 hours post- drug administration
measure: Steady-state plasma concentration of Dapagliflozin
timeFrame: 7 days
measure: Steady-state accumulation ratio of Dapagliflozin
timeFrame: 7 days
measure: Total mass of dapagliflozin extracted by the dialysis
timeFrame: 7 days
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: University of Campinas
state: SP
Study officials:
References: