Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients

NCT05343078 | Completed Phase 4

• 1 other identifier: 50393421.4.0000.5404
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

End-stage Renal Disease

Keywords

hemodialysis; dapagliflozin; peritoneal dialysis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Area under the curve of the plasma concentration-time curve of D3OG

  From dialysis initiation to 48 hours post- drug administration

• Steady-state plasma concentration of Dapagliflozin

  7 days

• Steady-state accumulation ratio of Dapagliflozin

  7 days

• Total mass of dapagliflozin extracted by the dialysis

  7 days

Study Arms (1)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10mg P.O.

Drug: Dapagliflozin 10Mg Tab

Interventions

Dapagliflozin 10Mg Tab DRUG

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.

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dialysis for 3 months or more prior to enrollment
• years of age or older
• Signed the informed consent form

You may not qualify if:

• Liver dysfunction
• Allergy to dapagliflozin
• Currently receiving a Sglt2i

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

University of Campinas

Campinas, São Paulo, 13083-887, Brazil

Location

Related Publications (1)

• Barreto J, Borges C, Rodrigues TB, Jesus DC, Campos-Staffico AM, Nadruz W, Luiz da Costa J, Bueno de Oliveira R, Sposito AC. Pharmacokinetic Properties of Dapagliflozin in Hemodialysis and Peritoneal Dialysis Patients. Clin J Am Soc Nephrol. 2023 Aug 1;18(8):1051-1058. doi: 10.2215/CJN.0000000000000196. Epub 2023 May 25.

  PMID: 37227937 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman of the Clinical Research Center

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 25, 2022
• Study Start: April 25, 2022
• Primary Completion: September 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)