A Multicenter, International, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Aldosterone Synthase Inhibitor BI 690517 in Combination With Empagliflozin in Patients With Chronic Kidney Disease
Overview
- Phase
- Phase 3
- Intervention
- Placebo matching BI 690517
- Conditions
- Kidney Disease, Chronic
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 11000
- Locations
- 758
- Primary Endpoint
- Time to first occurrence of the primary composite outcome of: (i) Kidney disease progression*; or (ii) Hospitalization for heart failure; or (iii) Cardiovascular death.
- Status
- Recruiting
- Last Updated
- 17 days ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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:
- •Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR ≥20 \<45 mL/min/1.73m²; or
- •CKD-EPI eGFR ≥45 \<90 mL/min/1.73m² with urine albumin-to-creatinine ratio (uACR) ≥200 mg/g (or protein-to-creatinine ratio ≥300 mg/g).
- •Neither requires an Aldosterone Synthase inhibitor (ASi) or Mineralocorticoid Receptor Antagonist (MRA), nor that such treatment is definitely inappropriate.
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
- •Known liver cirrhosis
- •On dialysis, functioning kidney transplant, or scheduled living donor transplant
- •Treated with new immunosuppression therapy for new (or relapse/flare of pre-existing) kidney disease within the last 60 days
- •Receiving more than one Renin-Angiotensin System (RAS) inhibitor (i.e. on dual therapy with two of an Angiotensin-Converting Enzyme inhibitor (ACEi), Angiotensin Receptor Blocker (ARB) or direct renin inhibitor)
- •Currently treated with an Mineralocorticoid Receptor Antagonist (MRA) (e.g. spironolactone, eplerenone, finerenone)
- •Currently treated with systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) Further exclusion criteria apply.
Arms & Interventions
Part 1: Run-in period (all participants)
Eligible participants will enter a Run-in period during which they will receive placebo matching BI 690517 + empagliflozin.
Intervention: Placebo matching BI 690517
Part 1: Run-in period (all participants)
Eligible participants will enter a Run-in period during which they will receive placebo matching BI 690517 + empagliflozin.
Intervention: Empagliflozin
Part 2: Randomized treatment, follow-up period, treatment group
Intervention: BI 690517
Part 2: Randomized treatment, follow-up period, treatment group
Intervention: Empagliflozin
Part 2: Follow-up period, placebo group
Intervention: Placebo matching BI 690517
Part 2: Follow-up period, placebo group
Intervention: Empagliflozin
Outcomes
Primary Outcomes
Time to first occurrence of the primary composite outcome of: (i) Kidney disease progression*; or (ii) Hospitalization for heart failure; or (iii) Cardiovascular death.
Time Frame: up to 4 years
Kidney disease progression is defined as kidney failure or a sustained decline of ≥40% in estimated Glomerular Filtration Rate (eGFR) from randomization
Secondary Outcomes
- Time to first event of kidney failure, hospitalization for heart failure or cardiovascular death(up to 4 years)
- Occurrences of hospitalizations for heart failure (first and any subsequent, combined) or cardiovascular death(up to 4 years)
- Occurrences of hospitalizations from any cause (first and any subsequent, combined)(up to 4 years)
- Time to first event of kidney disease progression or cardiovascular death(up to 4 years)
- Time to death from any cause(up to 4 years)
- Key secondary outcome: Annual rate of change in eGFR from 3 month visit until last scheduled visit (i.e. chronic eGFR slope)(up to 4 years)
- Time to kidney disease progression(up to 4 years)