Lorundrostat + Dapagliflozin for Kidney Disease

Recruiting at 44 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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind (DB), placebo controlled, crossover study with a two-period, two-sequence (2x2) design evaluating the efficacy and safety of 25 mg QD lorundrostat (an aldosterone synthase inhibitor \[ASI\]) in addition to a SGLT2i for the treatment of hypertension in subjects with CKD and albuminuria while receiving stable treatment with an Angiotensin-converting enzyme inhibitor (ACEi) or an Angiotensin receptor blocker (ARB). Subjects will be at least 18 years old with hypertension, and mild to severe CKD with albuminuria at the Screening Visit.

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.

What data supports the idea that Lorundrostat + Dapagliflozin for Kidney Disease is an effective drug?

The available research shows that dapagliflozin, a part of the Lorundrostat + Dapagliflozin combination, is effective in treating chronic kidney disease. In the DAPA-CKD trial, dapagliflozin significantly reduced the risk of kidney failure and prolonged survival in patients with chronic kidney disease, whether or not they had diabetes. The trial showed a 39% decline in the risk of worsening kidney function or kidney failure-related death. This suggests that the drug is effective in slowing down the progression of kidney disease and improving patient outcomes. ^{1 2 3 4 5}

What safety data exists for Lorundrostat + Dapagliflozin in kidney disease treatment?

The safety data for Dapagliflozin, a component of the treatment, includes studies on its effects on kidney function. A post-authorization safety study assessed hospitalization for acute kidney injury in patients with type 2 diabetes using Dapagliflozin. Another study reviewed adverse events of SGLT2 inhibitors, including Dapagliflozin, in chronic kidney disease. Additionally, research has shown that SGLT2 inhibitors can reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease. However, specific safety data for the combination of Lorundrostat and Dapagliflozin is not detailed in the provided research. ^{6 7 8 9 10}

Is the drug Lorundrostat a promising treatment for kidney disease?

The information provided focuses on dapagliflozin, which is shown to be effective in reducing kidney disease progression and related health issues. However, there is no specific information about Lorundrostat in the provided articles, so we cannot determine if it is a promising treatment for kidney disease based on this data. ^{1 2 4 5 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 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]

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]

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, 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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

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

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

Clinical Evaluation of Dapagliflozin in the Management of CKD: Focus on Patient Selection and Clinical Perspectives. [2022]

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

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin in people with chronic kidney disease. [2023]

6. New Zealand 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. [2023]

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

Adverse Events of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease: A Retrospective Chart Review. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

The effect of dapagliflozin on renal function in patients with type 2 diabetes. [2021]

9. England 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. [2023]

10. Ireland 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. [2023]

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

Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty. [2023]