BI 690517 + Empagliflozin for Chronic Kidney Disease

Recruiting at 82 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Boehringer Ingelheim

Must not be taking: MRAs, Dual RAS inhibitors

Disqualifiers: High potassium, Liver cirrhosis, Dialysis, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is open to adults with chronic kidney disease at risk of progression. People with and without type 2 diabetes can take part in this study. The study is open to people who take other medicines called angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). People who already take empagliflozin or any other sodium-glucose cotransporter-2 inhibitor (SGLT2i) can also join. The study is also open to people who currently do not take any of these treatments. The purpose of this study is to find out whether a medicine called BI 690517 helps people with chronic kidney disease when taken in combination with a study medicine called empagliflozin. Worsening of kidney function increases the risk for kidney failure, cardiovascular disease, and heart disease. This study has 2 parts. In the first part, participants get empagliflozin or placebo matching BI 690517 for at least 6 weeks. Participants continue taking ACEi or ARB throughout the study if such treatments are indicated. In the second part, participants are divided into 2 groups by chance. One group takes BI 690517 tablets and the other group takes placebo tablets. Placebo tablets look like BI 690517 tablets but do not contain any medicine. Participants take 1 tablet once a day in addition to empagliflozin for the duration of the study. The doctors document when participants experience worsening of their kidney disease, go to hospital due to heart failure, or die of cardiovascular problems during the study. The time to these events is compared between the 2 treatment groups to see whether the treatment works. The study continues until the required number of events have occurred which is about 3 to 4 years. During this time, participants visit the study site about 4 times within the first 6 months. Then they visit the study site every 6 months. At the visits, doctors regularly check participants' health, take blood and urine samples, measure blood pressure and weight, check kidney function, and take note of any unwanted effects.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if you are on ACE inhibitors or ARBs, as you can continue these throughout the study. However, if you are on more than one Renin-Angiotensin System inhibitor or certain other medications like MRAs, you may not be eligible to participate.

What data supports the effectiveness of the drug BI 690517 + Empagliflozin for chronic kidney disease?

Empagliflozin has been shown to reduce the progression of kidney disease and the risk of cardiovascular death in patients with chronic kidney disease. It is also effective in reducing the risk of hospitalization and cardiovascular death in heart failure patients, even those without diabetes. ^{1 2 3 4 5}

Is the treatment with BI 690517 and Empagliflozin safe for humans?

Empagliflozin (Jardiance) has been shown to be generally safe in humans, with some studies indicating it reduces the risk of heart-related issues and hospitalization in people with heart failure and chronic kidney disease. However, patients should be monitored for side effects like fluid deficits, and there is a possibility of increased fracture risk, similar to other drugs in its class. ^{1 2 3 4 6}

What makes the drug BI 690517 + Empagliflozin unique for treating chronic kidney disease?

This drug combination is unique because it includes empagliflozin, which is part of a new class of medications that lower blood sugar by preventing glucose reabsorption in the kidneys, and has shown benefits in reducing kidney disease progression and cardiovascular death in patients with chronic kidney disease. ^{1 6 7 8 9}

Eligibility Criteria

This trial is for adults with chronic kidney disease, including those with or without type 2 diabetes. It's open to patients taking ACEi or ARB medications and those not on any SGLT2 inhibitors like empagliflozin. Participants must have a certain level of kidney function (eGFR) and may have protein in their urine.

Inclusion Criteria

Evidence of chronic kidney disease (CKD) at risk of kidney disease progression is defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and requires:

My kidney function is low but not extremely severe.

I don't need, nor is it inappropriate for me to take, medications for hormone control.

Exclusion Criteria

Blood potassium of >5.2 mmol/L at screening visit

Blood Alanine Transaminase (ALT) or Aspartate Transaminase (AST) >3x Upper Limit of Normal (ULN) at Screening visit

I have been diagnosed with liver cirrhosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Eligible participants receive placebo matching BI 690517 + empagliflozin

6 weeks

4 visits (in-person) within the first 6 months

Randomized Treatment

Participants are divided into two groups: one receives BI 690517 and the other receives placebo, both in addition to empagliflozin

3-4 years

Every 6 months after the initial 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BI 690517 (Other)
• Empagliflozin (Other)
• Placebo matching BI 690517 (Other)

Trial Overview The study tests if BI 690517 combined with empagliflozin can protect against kidney disease progression compared to placebo. Initially, all participants receive empagliflozin or placebo for at least six weeks; then they're randomly assigned to add either BI 690517 or a placebo tablet daily.

Participant Groups

Group I: Part 2: Randomized treatment, follow-up period, treatment group Experimental Treatment 2 Interventions

Group II: Part 1: Run-in period (all participants) Experimental Treatment 2 Interventions

Eligible participants will enter a Run-in period during which they will receive placebo matching BI 690517 + empagliflozin.

Group III: Part 2: Follow-up period, placebo group Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

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 (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]

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[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, when administered to 15,081 patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD), showed no new safety concerns, with similar rates of serious adverse events compared to placebo.

The treatment was associated with significantly lower risks of hyperkalemia and edema, suggesting potential benefits for patients with advanced CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Tuttle, KR., Levin, A., Nangaku, M., et al.[2022]

The EMPA-KIDNEY trial is a large-scale study involving 6609 participants with chronic kidney disease (CKD) to assess the efficacy and safety of empagliflozin in reducing the risk of kidney disease progression and cardiovascular death.

Participants included individuals with varying degrees of kidney function and both diabetic and non-diabetic patients, making the results applicable to a broad population at risk for CKD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

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]

The EMPEROR-Reduced trial demonstrated that empagliflozin significantly improves heart failure outcomes in patients with reduced ejection fraction, showing benefits across various levels of kidney function.

Empagliflozin not only helps in managing heart failure symptoms but also provides protective effects on kidney function, making it a dual-action treatment for patients with both heart and kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In HFrEF, adding empagliflozin to medical therapy reduced a composite outcome, regardless of CKD status. Santos-Gallego, CG., Van Spall, HGC.[2021]

References

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

Diabetes Drug Now Approved for Heart Failure. [2023]

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

SGLT2 inhibitors: new reports. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. [2023]

5. Belgium pubmed.ncbi.nlm.nih.gov

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

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

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

8. 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]

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

In HFrEF, adding empagliflozin to medical therapy reduced a composite outcome, regardless of CKD status. [2021]