Empagliflozin for Polycystic Kidney Disease

Overseen By Michel B Chonchol, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Loop diuretics, Tolvaptan

Disqualifiers: Diabetes, Hypertension, Heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests empagliflozin, a drug that helps remove excess sugar through urine, in patients with ADPKD who suffer from kidney cysts and eventual kidney failure. The drug may help reduce kidney damage and improve heart health by blocking a protein that reabsorbs sugar. Empagliflozin has been shown to slow the progression of diabetic kidney disease.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as loop diuretics and tolvaptan or other V2 receptor antagonists, before participating.

Is empagliflozin generally safe for humans?

Empagliflozin, also known as Jardiance, is generally well-tolerated in humans, but it can have side effects and contraindications. It has been studied for safety in people with type 2 diabetes and heart failure, showing it is safe for these conditions, though monitoring for side effects like fluid deficits is recommended. ^{1 2 3 4 5}

How does the drug empagliflozin differ from other treatments for polycystic kidney disease?

Empagliflozin is unique because it is primarily used to treat type 2 diabetes by preventing glucose reabsorption in the kidneys, which also helps reduce blood pressure and body weight. Its potential use in polycystic kidney disease is novel, as it may help slow kidney disease progression, a benefit observed in chronic kidney disease patients. ^{1 6 7 8 9}

What data supports the effectiveness of the drug empagliflozin for treating polycystic kidney disease?

Research shows that empagliflozin, a drug used for chronic kidney disease, can slow down the progression of kidney disease and reduce the risk of heart-related deaths. This suggests it might also help with polycystic kidney disease, although specific studies for this condition are needed. ^{1 6 10 11 12}

Who Is on the Research Team?

Michel B Chonchol, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and moderately reduced kidney function, but not diabetes or heart failure. Participants should have stable kidney health without recent infections and must not be pregnant, using certain diuretics, or have contraindications to MRI scans.

Inclusion Criteria

I have been diagnosed with ADPKD according to specific criteria.

My kidney function has been stable for the last 3 months.

You have been categorized as having a specific risk level based on imaging tests done at the Mayo Clinic.

Exclusion Criteria

Your blood pressure while sitting is less than 100 mm Hg.

I am currently taking tolvaptan or a similar medication.

Pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin or placebo in a 12-month parallel-group, randomized, double-blind, placebo-controlled trial

12 months

Check-in visits every 2 weeks for the 1st month, monthly on month 2 and 3, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Placebo

Trial Overview The study tests the safety of Empagliflozin in ADPKD patients over a year. It's a double-blind trial where half the participants will receive Empagliflozin and the other half a placebo, neither group knowing which they're getting to ensure unbiased results.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Empagliflozin

Group II: Placebo comparator Placebo Group 1 Intervention

Placebo

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Published Research Related to This Trial

The EMPA-KIDNEY study evaluated the effects of empagliflozin in patients with chronic kidney disease, demonstrating significant benefits in slowing the progression of kidney disease.

This study involved a large cohort of patients, providing robust evidence for the efficacy of empagliflozin as a treatment option for chronic kidney disease, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. Kwong, YD., Hsu, CY.[2023]

In the EMPA-KIDNEY trial involving 6609 patients with chronic kidney disease, empagliflozin significantly reduced the risk of kidney disease progression or death from cardiovascular causes compared to placebo, with a hazard ratio of 0.72, indicating a 28% lower risk.

Patients taking empagliflozin also experienced fewer hospitalizations for any cause compared to those on placebo, suggesting a potential safety benefit, although there were no significant differences in heart failure hospitalizations or overall mortality between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin in Patients with Chronic Kidney Disease. Herrington, WG., Staplin, N., Wanner, C., et al.[2023]

In the EMPA-KIDNEY trial involving 6609 participants, empagliflozin significantly slowed the progression of chronic kidney disease, reducing the chronic decline in kidney function by 50% after an initial dip in eGFR.

The benefits of empagliflozin were observed across various patient groups, indicating that albuminuria levels should not be the sole factor in deciding treatment with SGLT2 inhibitors, as even patients with low albuminuria experienced significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

In the DAPA-CKD study involving 4,304 participants with chronic kidney disease, dapagliflozin significantly reduced the risk of kidney and cardiovascular events across different glycemic statuses, including normoglycemia, prediabetes, and type 2 diabetes.

The treatment was found to be safe, with no major incidents of hypoglycemia or ketoacidosis reported, indicating that dapagliflozin can be effectively used in patients regardless of their baseline blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial. Persson, F., Rossing, P., Vart, P., et al.[2021]

The study found that a generic empagliflozin tablet is bioequivalent to the brand-named Jardiance® in terms of key pharmacokinetic parameters, indicating that both formulations can be expected to have similar efficacy and safety profiles in healthy individuals.

Consumption of high-fat food did not affect the pharmacokinetics of empagliflozin, suggesting that it can be taken with or without food without impacting its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of a generic empagliflozin tablet versus a brand-named product and the food effects in healthy Chinese subjects. Li, X., Liu, L., Deng, Y., et al.[2021]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

Empagliflozin (10 mg and 25 mg) is well tolerated in patients with type 2 diabetes mellitus (T2DM), showing similar rates of adverse events compared to placebo across a pooled analysis of 20 clinical trials involving over 14,000 participants.

While empagliflozin did not significantly increase the risk of hypoglycemia or urinary tract infections compared to placebo, it was associated with a higher incidence of genital infections, highlighting the need for monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Safety and Tolerability Analysis of Empagliflozin in Patients with Type 2 Diabetes Mellitus. Kinduryte Schorling, O., Clark, D., Zwiener, I., et al.[2022]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

Empagliflozin, an SGLT2 inhibitor, is effective in managing blood glucose levels and reducing cardiovascular risks in patients with type 2 diabetes, but it can also lead to euglycemic diabetic ketoacidosis under certain conditions, such as acute illness or reduced carbohydrate intake.

A case study of a 23-year-old female with poorly controlled diabetes on empagliflozin revealed severe euglycemic metabolic acidosis and elevated urine ketones during a COVID-19 infection, highlighting the need for careful monitoring in patients using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Severe Metabolic Acidosis due to Jardiance-Induced Euglycemic Diabetic Ketoacidosis. Dyatlova, N., Omotosho, YB., Sherchan, R., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of a generic empagliflozin tablet versus a brand-named product and the food effects in healthy Chinese subjects. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Pooled Safety and Tolerability Analysis of Empagliflozin in Patients with Type 2 Diabetes Mellitus. [2022]

10. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]

11. Czech Republic pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

A Case of Severe Metabolic Acidosis due to Jardiance-Induced Euglycemic Diabetic Ketoacidosis. [2021]