BI 690517 + Empagliflozin for Chronic Kidney Disease

No longer recruiting at 278 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boehringer Ingelheim

Must be taking: ACE inhibitors, ARBs

Must not be taking: Aldosterone inhibitors, SGLT inhibitors

Disqualifiers: Type 1 diabetes, Ketoacidosis risk, others

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

Compensation: Varies

Number of Visits: 12

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new medicine, BI 690517, can improve kidney function in individuals with chronic kidney disease, either alone or in combination with empagliflozin (Jardiance). Participants will take varying doses of these medicines over several months to assess their impact on kidney health. This trial suits individuals diagnosed with chronic kidney disease, with or without type 2 diabetes, who experience related symptoms in daily life. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop certain medications, like mineralocorticoid receptor antagonists or other potassium-sparing diuretics, before joining the trial. However, if you're on medications like anti-hypertensives or ACE inhibitors, you should stay on a stable dose throughout the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that BI 690517 is generally well tolerated by people with chronic kidney disease. Earlier research demonstrated that this treatment helped reduce certain hormone levels and may lower protein in urine, a positive sign for kidney health. However, these studies primarily focused on safety in small groups.

Empagliflozin, in contrast, has been widely used and is known to be safe for people with type 2 diabetes. It is also considered safe for people without diabetes and older adults, even those with reduced kidney function, as multiple studies have confirmed.

In summary, while empagliflozin has a strong safety record, BI 690517 has shown promise and is generally well tolerated in earlier studies. Participants in the study will receive regular monitoring to check for any unwanted effects and ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for chronic kidney disease (CKD) focus on controlling symptoms and slowing progression, often using blood pressure medications like ACE inhibitors or ARBs. But BI 690517, sometimes paired with empagliflozin, offers a new approach by targeting different pathways. BI 690517 is intriguing because it acts as a soluble guanylate cyclase (sGC) stimulator, potentially improving kidney function by enhancing blood flow and reducing inflammation. Meanwhile, empagliflozin, a well-known SGLT-2 inhibitor, helps manage glucose levels and may offer kidney protection. Researchers are excited about the combination because it could provide a dual benefit: improving kidney outcomes while also controlling blood sugar, offering a fresh hope for people with CKD.

What evidence suggests that this trial's treatments could be effective for chronic kidney disease?

Research has shown that BI 690517, one of the investigational treatments in this trial, may help reduce kidney damage by lowering albuminuria, a sign of kidney damage. Studies found that BI 690517 can reduce albuminuria by up to 39.5%. Empagliflozin, another treatment option in this trial, is already known to improve kidney and heart health in people with type 2 diabetes. When used with empagliflozin, as tested in some arms of this trial, BI 690517 may have an even stronger combined effect, offering additional benefits. This combination targets both kidney and heart health, showing promise for people with chronic kidney disease. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Urine Albumin Creatinine Ratio (UACR) ≥ 200 and < 5,000 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.1

Treatment with a clinically appropriate, stable dose of either Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both together), for ≥ 4 weeks prior to visit 1 and until first randomisation with no planned change of the therapy during the trial.

In the Investigator's opinion, any kind of diagnosed chronic kidney disease (Diagnosis can be reached by standard clinical method, no biopsy required). Patients with diabetic kidney disease must have type 2 diabetes mellitus and their treatment (including GLP1 receptor agonist) should be unchanged or changes deemed minor (according to investigator's judgement) within 4 weeks prior to Visit 1 and until first randomisation.

Exclusion Criteria

The doctor believes that you may be at risk of ketoacidosis.

You have type 1 diabetes or other forms of autoimmune-related diabetes.

Treatment with inhibitors of aldosterone mediated effects (e.g., mineralocorticoid receptor antagonists such as spironolactone), or intake of other potassium sparing diuretics (e.g., amiloride) within 7 days prior to first randomisation or planned during trial treatment phase.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants take empagliflozin or placebo as tablets every day

8 weeks

4 visits (in-person), 2 visits (virtual)

Treatment

Participants take different doses of BI 690517 or placebo in addition to empagliflozin or placebo

14 weeks

8 visits (in-person), 2 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 690517
• Empagliflozin
• Not Applicable
• Placebo to BI 690517
• Placebo to Empagliflozin

How Is the Trial Designed?

Group I: Treatment period: Placebo to empagliflozin 10 mg + 3 mg BI 690517 Experimental Treatment 2 Interventions

Group II: Treatment period: Placebo to empagliflozin 10 mg + 20 mg BI 690517 Experimental Treatment 2 Interventions

Group III: Treatment period: Placebo to empagliflozin 10 mg + 10 mg BI 690517 Experimental Treatment 2 Interventions

Group IV: Treatment period: 10 mg empagliflozin + 3 mg BI 690517 Experimental Treatment 2 Interventions

Group V: Treatment period: 10 mg empagliflozin + 20 mg BI 690517 Experimental Treatment 2 Interventions

Group VI: Treatment period: 10 mg empagliflozin + 10 mg BI 690517 Experimental Treatment 2 Interventions

Group VII: Run-in period: 10 mg empagliflozin Experimental Treatment 1 Intervention

Group VIII: Treatment period: 10 mg empagliflozin + Placebo to BI 690517 Placebo Group 2 Interventions

Group IX: Treatment period: Placebo to empagliflozin 10 mg + Placebo to BI 690517 Placebo Group 2 Interventions

Group X: Run-in period: Placebo to empagliflozin 10 mg Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Empagliflozin, a medication for type 2 diabetes, showed similar maximum plasma concentrations in individuals with normal kidney function and those with varying degrees of renal impairment, indicating consistent absorption regardless of kidney health.

The study found that empagliflozin was well tolerated across all levels of renal impairment, with no need for dose adjustments, suggesting it is a safe option for patients with kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Macha, S., Mattheus, M., Halabi, A., et al.[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 (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 is an effective oral medication for type 2 diabetes that works independently of insulin, showing improvements in blood glucose levels, body weight, and blood pressure across various patient populations.

It has been found to be well tolerated with no increased risk of hypoglycemia compared to placebo, making it a safe option for managing diabetes either alone or in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. White, JR.[2018]

Empagliflozin (Jardiance) is an effective once-daily treatment for type 2 diabetes that works by inhibiting glucose reabsorption in the kidneys, leading to improved blood sugar control, weight loss, and reduced blood pressure, as shown in phase III trials lasting up to 104 weeks.

In a large trial, empagliflozin was found to be noninferior to glimepiride and even superior at 104 weeks in lowering glycated hemoglobin levels, with a good safety profile and minimal risk of hypoglycemia, especially when not used with insulin or sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: a review of its use in patients with type 2 diabetes mellitus. Scott, LJ.[2021]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39533115/

a rationale for the EASi-KIDNEY trial Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to ...

2. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/chronic-kidney-disease/promising-phase-ii-results-chronic-kidney-disease

Promising phase II results in chronic kidney disease Phase II results demonstrated significant albuminuria reductions by up to 39.5% vs. placebo when BI 690517, a novel selective aldosterone ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362302408X

Efficacy and safety of aldosterone synthase inhibition with ... This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05182840

NCT05182840 | A Study to Test Whether Different Doses of ... The purpose of this study is to find out whether a medicine called BI 690517 improves kidney function in people with chronic kidney disease when taken alone or ...

5. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15518

Aldosterone synthase inhibitor (BI 690517) therapy for ... BI 690517 was generally well tolerated, reduced plasma aldosterone and may decrease albuminuria in participants with diabetes and albuminuric chronic kidney ...

6. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/clinical-pipeline/vicadrostat-bi-690517-empagliflozin

Vicadrostat (BI 690517) / empagliflozin Indication: Chronic kidney disease. Boehringer Ingelheim is investigating the potential benefits of vicadrostat (BI 690517)/empagliflozin, a novel selective ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12263707/

Phase 1 studies of the safety, tolerability, pharmacokinetics ... We report safety results for BI 690517 (vicadrostat), a potent, selective aldosterone synthase inhibitor under investigation for CKD.