Dapagliflozin in Non-diabetic Stage IV CKD

NCT04794517 | Completed Phase 2

• 2 other identifiers: ADAPT2021-000726-10
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2b, prospective, randomized, cross-over, double-blind, placebo-controlled trial primarily aimed at assessing whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (\>0.5 g/24 hours). The study will also evaluate renal and systemic mechanisms mediating treatment effects on GFR and will explore biochemical factors possibly mediating these effects.

Conditions

Chronic Kidney Diseases

Keywords

Chronic kidney disease; Proteinuria; Dapagliflozin

Outcome Measures

Primary Outcomes (2)

• Glomerular Filtration rate (GFR)

  GFR measured by the Iohexol plasma clearance technique

  Changes from baseline and day 1, 8, 42,84, 92,126 and 140.

• 24-hour urinary protein excretion

  24-hour urinary protein excretion will be measured as median of three measurements in three consecutive 24-hour urine collections

  Changes from start (day 0, day 84) and end (day 42, day 126) of each Treatment Period with dapagliflozin or placebo

Secondary Outcomes (1)

• Renal plasma flow (RPF)

  Changes from baseline and day 1, 8, 42,84, 92,126 and 140.

Study Arms (2)

IMP

EXPERIMENTAL

Dapagliflozin 10 mg/die will be administered orally for six-weeks.

Drug: Dapagliflozin 10Mg Tab

Placebo

PLACEBO COMPARATOR

Placebo, one tablet/die will be administered orally for six-weeks.

Other: Placebo

Interventions

Dapagliflozin 10Mg Tab DRUG

Dapagliflozin 10 mg/die will be administered orally for six-weeks.

IMP

Placebo OTHER

Placebo one tablet/die will be administered orally for six-weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Male or female more than 18 year old
• Non-diabetic Stage-IV CKD
• Fasting blood glucose ≤ 125 mg (≤ 6.9 mmol/l) and HbA1C ≤6.4% (≤ 47 mmol/mol)58 without treatment with oral blood glucose lowering medications and/or insulin
• Two-hour plasma glucose \<200 mg/dl during 75-g oral glucose tolerance test (OGTT)58
• Persistent proteinuria (24-hour urinary protein excretion ≥ 0.5 grams in at least two consecutive evaluations \>1 week apart) despite RAS inhibitor therapy with ACE inhibitors and/or ARBs (or without RAS inhibitors in patients with specific contraindications to these medications)
• eGFR 15 to 30 ml/min/1.73 m2 by CKD-Epi equation
• Blood pressure \<150/90 mmHg without changes in blood pressure lowering medications over the last four weeks before the randomization
• Negative pregnancy test (urine or serum) for female subjects of childbearing potential.10
• Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of dapagliflozin\\placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
• Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of IMP to prevent pregnancy in a partner.
• Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of dapagliflozin\\placebo.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Participation in another clinical study with an investigational product during the last month
• Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2-inhibitor associated reduction in sodium pool and kidney perfusion pressure)
• Rapidly progressive kidney disease (e GFR reduction ≥ 30% over the last three months) and expected risk of progression to end stage kidney failure and need of renal replacement therapy by dialysis or transplantation during the study period.
• Active systemic autoimmune diseases;
• Concomitant treatment with steroids or any other immunosuppressive agent
• Hypersensitivity to the active principle (dapagliflozin) or any of the excipients (e.g. lactose);
• Severe/unstable heart failure with or without decreased systolic function requiring hospitalization or changes in pharmacological therapy over the last three months
• Uncontrolled hypertension (BP \>150/90 mmHg despite optimized pharmacological treatment and diet or symptomatic hypotension
• Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening
• Known to have tested positive for human immunodeficiency virus
• Drug or alcohol abuse
• Inability to fully understand the possible risks and benefits related to study participation
• If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
• If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• AstraZeneca: collaborator

Study Sites (1)

Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Proteinuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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; Urination Disorders; Urological Manifestations; Signs and Symptoms

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 12, 2021
• Study Start: November 8, 2021
• Primary Completion: May 7, 2024
• Study Completion: May 7, 2024
• Last Updated: May 10, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)