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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called empagliflozin (Jardiance) to determine its safety and tolerability for individuals with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Researchers aim to compare the effects of empagliflozin with a placebo (a pill with no active drug) over 12 months. The trial seeks participants with ADPKD who have maintained a certain level of kidney function and stable kidney health over the past three months. Eligible participants should not have diabetes or certain heart conditions and should not be using specific medications like loop diuretics. For those with ADPKD who meet these criteria, this trial might be a suitable option. As a Phase 2 trial, this research measures how well empagliflozin works in an initial, smaller group, offering a chance to contribute to important findings.

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 there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research shows that empagliflozin is generally safe for people with certain kidney and heart conditions. Studies have found that it can reduce the risk of worsening kidney disease and may help prevent heart issues. In patients with type 2 diabetes and advanced chronic kidney disease (CKD), empagliflozin did not cause any unexpected safety problems, meaning people did not experience surprising adverse reactions to the treatment.

In trials for autosomal dominant polycystic kidney disease (ADPKD), researchers are carefully monitoring empagliflozin for safety. They observe how people respond to the drug and check for any side effects. Overall, evidence so far suggests that empagliflozin is well-tolerated by patients, meaning most people can take this medication without serious issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for polycystic kidney disease?

Empagliflozin is unique because it targets polycystic kidney disease (PKD) by inhibiting a protein called SGLT2, which plays a role in glucose reabsorption in the kidneys. Unlike the standard treatments for PKD, which often focus on managing symptoms like hypertension and pain, empagliflozin directly affects kidney function by promoting glucose excretion in urine. This mechanism not only helps in potentially slowing cyst growth and preserving kidney function but also offers the added benefit of improving blood sugar control, which is not addressed by current PKD treatments. Researchers are excited about empagliflozin because it represents a novel approach that could offer more comprehensive benefits to PKD patients.

What evidence suggests that empagliflozin might be an effective treatment for ADPKD?

Research has shown that empagliflozin, which participants in this trial may receive, may help with kidney problems. Studies have found that it can slow kidney disease and reduce the risk of death related to it. For individuals with long-term kidney disease, empagliflozin performed better than a placebo, improving their quality of life and lowering healthcare costs. Although more research is needed for polycystic kidney disease, these findings suggest potential benefits. Participants in this trial will receive either empagliflozin or a placebo to evaluate its effectiveness specifically for polycystic kidney disease. ^{1 2 4 6 7}

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

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]

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 (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 (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]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11647394/

Empagliflozin in patients with autosomal dominant ... The EMPA-PKD trial is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06391450

NCT06391450 | Study of Empagliflozin in Patients with ... The primary endpoint is progression of cystic kidney growth by monitoring MRI-based changes in total kidney volume and the secondary endpoint is exploring ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204233

Empagliflozin in Patients with Chronic Kidney Disease Empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025002706

Effects of empagliflozin on quality of life and healthcare use ... We report that allocation to empagliflozin in EMPA-KIDNEY increased quality-of-life-adjusted survival and reduced the use and cost of other healthcare over 2 ...

5. academic.oup.com academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaf061/8108808

SGLT2 inhibition for patients with ADPKD - Oxford Academic This review summarizes the current knowledge on SGLT2i in this specific patient population and outlines running and upcoming clinical trial programs.

6. diabetesjournals.org diabetesjournals.org/care/article/45/6/1445/145036/Safety-of-Empagliflozin-in-Patients-With-Type-2

Safety of Empagliflozin in Patients With Type 2 Diabetes and ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...

7. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(23)00322-4/fulltext

secondary analyses of the EMPA-KIDNEY trial The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in ...