A Study to Test Whether Different Doses of BI 690517 Alone or in Combination With Empagliflozin Improve Kidney Function in People With Chronic Kidney Disease

Recruiting at 250 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

714 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug empagliflozin?

Empagliflozin, a drug used for type 2 diabetes, helps lower blood sugar by preventing glucose reabsorption in the kidneys, leading to weight loss and reduced blood pressure. It has also been approved to reduce the risk of heart-related issues in people with heart failure, even if they don't have diabetes. ^{1 2 3 4 5}

How is the drug Empagliflozin unique compared to other treatments for type 2 diabetes?

Empagliflozin is unique because it lowers blood sugar by preventing the kidneys from reabsorbing glucose, leading to its excretion in urine, which is different from many other diabetes drugs that work by affecting insulin. This mechanism also helps with weight loss and reduces blood pressure, offering additional benefits beyond glucose control. ^{1 2 5 6 7}

What is the purpose of this trial?

This trial tests whether a new medicine, BI 690517, alone or with empagliflozin, can improve kidney function in adults with chronic kidney disease. The study includes people with and without type 2 diabetes. The goal is to see if these medicines can help the kidneys work better.

Eligibility Criteria

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

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

Treatment Details

Interventions

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

Participant Groups

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

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

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

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 (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 (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 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 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, 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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Diabetes Drug Now Approved for Heart Failure. [2023]

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

Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. [2022]

5. 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]

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

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

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

Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. [2022]