Lorundrostat + Dapagliflozin for Kidney Disease

No longer recruiting at 45 trial locations

Overseen By Ebony Clayton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mineralys Therapeutics Inc.

Must be taking: ACEi, ARB, SGLT2i

Must not be taking: ENaC inhibitors, MRAs

Disqualifiers: Hypersensitivity, Advanced liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with chronic kidney disease (CKD) who also have high blood pressure and protein in their urine. The study examines how lorundrostat, a drug that blocks a hormone known to raise blood pressure, works with dapagliflozin, a medication used to lower blood sugar and blood pressure, to safely reduce blood pressure. It targets those who have maintained a stable regimen, including an ACE inhibitor or ARB, for at least two months. Participants should have CKD with protein in their urine and manage high blood pressure between 135-180 mmHg. This trial may suit those who haven't found relief from current treatments and experience these specific symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

Do I have to stop taking my current medications?

The trial requires you to stay on a stable treatment with an ACE inhibitor or an Angiotensin receptor blocker for at least 2 months before screening. You cannot use epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists from 4 weeks before screening and during the study.

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

Research has shown that lorundrostat, a medication that blocks a hormone involved in blood pressure regulation, is generally well-tolerated. In studies, individuals with high blood pressure experienced significant reductions without major safety issues. Most side effects were mild, such as dizziness and tiredness.

Studies have also shown that dapagliflozin, a medication that helps the kidneys remove sugar from the body, is safe for people with chronic kidney disease (CKD). It has a good safety record, with no serious side effects like diabetic ketoacidosis (a dangerous condition where acids build up in the blood) reported in patients, whether or not they have type 2 diabetes.

Both lorundrostat and dapagliflozin have shown promising safety results in previous research, suggesting they could be safe options for people with CKD and high blood pressure. ^{1 2 3 4 5}

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

Unlike the standard treatments for kidney disease, which often include blood pressure medications and diuretics, Lorundrostat offers a new approach by targeting the aldosterone pathway. This pathway is crucial because aldosterone can contribute to kidney damage by causing inflammation and fibrosis. Researchers are excited about Lorundrostat because it may protect the kidneys more effectively by directly reducing aldosterone production, potentially slowing down the progression of kidney disease. This mechanism of action is different from current options and could offer a new hope for patients with kidney disease.

What evidence suggests that this trial's treatments could be effective for hypertension in CKD patients?

This trial will evaluate the effects of Lorundrostat and Dapagliflozin on kidney disease. Research has shown that Lorundrostat, which participants in this trial may receive, can lower blood pressure and reduce protein in the urine for people with chronic kidney disease (CKD) and high blood pressure. In one study, patients taking Lorundrostat experienced a 9.3 mmHg drop in systolic blood pressure. Another study found that it lowered both blood pressure and the urine albumin-to-creatinine ratio, a key marker of kidney health.

Dapagliflozin, another treatment option in this trial, is already known to slow the progression of kidney disease. Research has shown it can delay the onset of kidney failure by more than six years. These findings suggest that both Lorundrostat and Dapagliflozin may benefit those managing kidney disease and high blood pressure. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with chronic kidney disease and high levels of protein in their urine (albuminuria), who also have high blood pressure. They should be on stable heart medication (ACEi or ARB) for at least 2 months, with specific ranges of kidney function and body mass index.

Inclusion Criteria

I have been on a stable dose of ACE inhibitor or ARB medication for at least 2 months.

Your body mass index (BMI) is between 18 and 45.

Your blood pressure is between 135 and 160 mmHg when measured at the start of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Subjects will either begin study provided dapagliflozin 10 mg or continue on their regularly prescribed SGLT2i

2 weeks

Treatment Period 1

Subjects receive either lorundrostat or placebo in a double-blind manner

4 weeks

Washout

A period where no study drug is administered to clear the effects of the previous treatment

4 weeks

Treatment Period 2

Subjects receive the alternate treatment (lorundrostat or placebo) in a double-blind manner

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Lorundrostat

Trial Overview The study tests Lorundrostat, a drug that may help control blood pressure by inhibiting aldosterone production, alone or combined with Dapagliflozin. It's divided into two parts to assess effectiveness and safety in different stages of kidney disease.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

Group II: Cohort 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Mineralys Therapeutics Inc.

Lead Sponsor

Trials

6

Recruited

3,100+

Founded

2019

Headquarters

Radnor, USA

Known For

Hypertension treatments

Top Products

Lorundrostat

Published Research Related to This Trial

Dapagliflozin has been shown to significantly improve kidney outcomes in patients with chronic kidney disease, demonstrating its efficacy in reducing the risk of kidney disease progression.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of dapagliflozin in managing chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality. Molony, DA., LeMaistre, FI.[2021]

In a study involving 624 participants with stage 4 chronic kidney disease (CKD), dapagliflozin significantly reduced the risk of kidney failure and prolonged survival, showing a 27% reduction in the primary composite endpoint compared to placebo.

Dapagliflozin was found to be safe, with similar rates of serious adverse events between the treatment and placebo groups, indicating that it can be an effective option for patients with advanced CKD without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. Chertow, GM., Vart, P., Jongs, N., et al.[2023]

Dapagliflozin, used to treat type 2 diabetes, showed only small and temporary reductions in kidney function (eGFR) at week 1, which returned to baseline by week 24 and remained stable up to 102 weeks, indicating its renal safety.

The frequency of renal adverse events with dapagliflozin was similar to that of placebo, with very few serious events reported, suggesting that dapagliflozin does not increase the risk of acute renal toxicity in patients with normal or mildly impaired kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of dapagliflozin on renal function in patients with type 2 diabetes. Kohan, DE., Fioretto, P., Johnsson, K., et al.[2021]

Dapagliflozin, an SGLT2 inhibitor, is effective in treating type 2 diabetes and has been shown to significantly reduce cardiovascular and major renal events in clinical trials.

In the DAPA-CKD trial, dapagliflozin notably decreased the risk of kidney disease progression in patients with chronic kidney disease, making it a valuable treatment option for both diabetic and non-diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. Kelly, MS.[2022]

Dapagliflozin significantly reduced the risk of serious kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) across all levels of frailty, demonstrating its efficacy regardless of frailty status.

The safety profile of dapagliflozin was consistent across frailty categories, with a lower occurrence of serious adverse events compared to placebo, indicating it is a safe treatment option for frail patients with CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty. Vart, P., Butt, JH., Jongs, N., et al.[2023]

In a study of 213 patients with type 2 diabetes and chronic kidney disease, urinary tract infections and genital mycotic infections were the most common adverse events associated with SGLT2 inhibitors, occurring at rates of 62.1 and 58.0 events per 1000 person-years, respectively.

Despite these adverse events, SGLT2 inhibitors led to favorable changes in kidney function markers, with significant decreases in urine albumin-to-creatinine ratios and hemoglobin A1c percentages, indicating their efficacy in managing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease: A Retrospective Chart Review. Choi, H., Nguyen, LA., Wan, J., et al.[2022]

Dapagliflozin has been shown to be effective in improving outcomes for patients with chronic kidney disease, as highlighted in the commentary on a study involving diverse patient populations.

The commentary emphasizes the importance of dapagliflozin's mechanism of action, which includes reducing the risk of kidney disease progression and cardiovascular events, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin in people with chronic kidney disease. Sylvester, RD., Khong, TK.[2023]

In a study involving over 34,000 person-years of real-world exposure, dapagliflozin was associated with a significantly lower incidence of hospitalization for acute kidney injury (hAKI) compared to other glucose-lowering drugs, indicating a safer profile for kidney function.

The adjusted incidence rate ratios showed that dapagliflozin users had a 30% reduced risk of hAKI, supporting its safety and efficacy in treating type 2 diabetes mellitus without compromising kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting. Johannes, CB., Beachler, DC., Layton, JB., et al.[2023]

Dapagliflozin, an SGLT2 inhibitor, significantly reduces the risk of worsening kidney function and related complications by 39%, as demonstrated in the DAPA-CKD trial involving adults with chronic kidney disease, regardless of diabetes status.

The drug's protective effects on the kidneys are thought to arise from various mechanisms, including improved blood pressure control, better salt sensitivity, and reductions in glucose, uric acid, and triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Dapagliflozin in the Management of CKD: Focus on Patient Selection and Clinical Perspectives. Nashar, K., Khalil, P.[2022]

Sotagliflozin, a new medication for diabetes, was found to be safe for renal function, showing no significant adverse effects on kidney health in a review of 14 studies involving 17,574 participants, including those with existing renal impairment.

The drug did not significantly change urinary albumin excretion or the risk of composite renal events, indicating that while it is safe, more research is needed to fully understand its effectiveness in preventing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Bantounou, MA., Sardellis, P., Thuemmler, R., et al.[2023]

In a study of 1,450 type 2 diabetic patients with advanced chronic kidney disease (CKD), SGLT2 inhibitors significantly reduced the rates of kidney-related adverse events (7.7% vs. 24.1%) and major adverse cardiovascular events (MACE) (9.6% vs. 15.1%) compared to a control group.

Patients using SGLT2 inhibitors also showed improved kidney function (eGFR increased by 0.4 ml/min/1.73 m²) and better glycemic control (HbA1c decreased by -0.40%), with only a slight increase in urinary tract infections, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease: A population-based propensity score-matched cohort study. Chan, GC., Ng, JK., Chow, KM., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38730538/

The long-term effects of dapagliflozin in chronic kidney ... Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) ...

2. farxiga-hcp.com farxiga-hcp.com/chronic-kidney-disease

Chronic Kidney Disease | FARXIGA® (dapagliflozin) 5 mg ... The primary efficacy endpoint was a composite of sustained ≥50% eGFR decline, ESKD, or CV or renal death. 97% of patients received a stable dose of ACEi/ARB ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024816

Dapagliflozin in Patients with Chronic Kidney Disease The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2021/farxiga-approved-in-the-us-for-ckd.html

Farxiga approved in the US for the treatment of chronic ... In August 2020, results from the DAPA-CKD Phase III trial demonstrated that Farxiga achieved unprecedented reduction in the composite risk of ...

5. academic.oup.com academic.oup.com/ndt/article/39/12/2040/7668437

The long-term effects of dapagliflozin in chronic kidney disease Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39834621/

Efficacy and safety of dapagliflozin in patients with CKD Albuminuria reduction was ≥30% in 48.3% of patients, 0-29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, ...

7. hfsa.org hfsa.org/farxiga-demonstrated-unprecedented-reduction-risk-kidney-failure-and-cardiovascular-or-renal-death

Farxiga demonstrated unprecedented reduction in the risk ... Farxiga demonstrated unprecedented reduction in the risk of kidney failure and cardiovascular or renal death in patients with chronic kidney disease in the ...