Efficacy and Safety of Baxdrostat and Dapagliflozin on Renal and Cardiovascular Outcomes in Chronic Kidney Disease with Hypertension
- Trial ID
- 2023-506460-14-00
- Protocol
- D6972C00002
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate whether the combination of **baxdrostat** and dapagliflozin is superior to placebo and dapagliflozin in reducing the risk of a composite endpoint. This endpoint includes a ≥50% sustained decline in estimated glomerular filtration rate (eGFR), kidney failure, or cardiovascular (CV) death. This is clinically relevant as it addresses critical outcomes in patients with chronic kidney disease (CKD) and hypertension, potentially improving renal and cardiovascular health.
Secondary objectives include: - Determining whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing urinary albumin-to-creatinine ratio (UACR). - Assessing the superiority of baxdrostat/dapagliflozin over placebo/dapagliflozin in reducing systolic blood pressure (SBP). - Evaluating the reduction in the risk of major adverse cardiovascular events (MACE), including CV death, heart failure (HF) events, myocardial infarction (MI), and stroke. - Investigating the reduction in the risk of CV death. - Assessing the reduction in the risk of all-cause death.
Participants
The clinical trial involves a total of **3,590 participants** diagnosed with **chronic kidney disease (CKD)** and **hypertension**. The study population includes adults of any sex and gender, aged 18 years and older. Participants were selected based on specific health criteria, including an estimated glomerular filtration rate (eGFR) between 30 and 75 mL/min/1.73 m² and a urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR) within defined ranges. All participants have a history of hypertension with a systolic blood pressure (SBP) of at least 130 mmHg. They are required to be on a stable and maximum tolerated dose of either an ACE inhibitor or an angiotensin receptor blocker (ARB) for at least four weeks prior to the screening visit. The trial includes both male and female subjects and considers vulnerable populations. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, event-driven study designed to evaluate the efficacy, safety, and tolerability of **Baxdrostat** in combination with **Dapagliflozin** compared to Dapagliflozin alone. The trial targets participants with **chronic kidney disease (CKD)** and **hypertension**. The primary objective is to determine whether the combination therapy is superior in reducing the risk of a composite endpoint, including a ≥50% sustained decline in estimated glomerular filtration rate (eGFR), kidney failure, or cardiovascular (CV) death. The trial is expected to commence recruitment on April 15, 2025, and conclude by May 20, 2030.
Participants will be involved in the study for a maximum treatment period of 60 to 61 days, depending on the specific treatment arm. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, eGFR, urinary albumin-to-creatinine ratio (UACR), and blood pressure. Following randomization, participants will attend regular follow-up visits to monitor safety, efficacy, and adherence to the treatment regimen. The end-of-study visit will assess the final outcomes and any adverse events. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety.
The trial will utilize oral administration of the investigational products, with **Baxdrostat** and **Dapagliflozin** provided in tablet form. A placebo group will be included to ensure the robustness of the study's findings. The primary endpoint is the time to the first occurrence of any component of the composite endpoint, while secondary endpoints include changes in UACR, mean systolic blood pressure (SBP), and time to CV events such as heart failure, myocardial infarction, or stroke. The study's design and methodology aim to provide comprehensive data on the potential benefits of the combination therapy in the target population.
Treatment
The clinical trial involves the administration of **Baxdrostat**, a synthetic small molecule, as an experimental medication. Baxdrostat is provided in the form of a tablet and is administered orally. The maximum treatment period for Baxdrostat is 60 days. The specific dosage and frequency of administration are not detailed in the provided data. The active substance, Baxdrostat, is of chemical origin and is manufactured by AstraZeneca AB. Participant compliance with the dosing regimen will be monitored throughout the study.
In addition to Baxdrostat, the trial includes the administration of **Dapagliflozin**, marketed as Forxiga 10 mg film-coated tablets. Dapagliflozin is also a synthetic small molecule and is administered orally. The maximum daily dose for Dapagliflozin is 10 mg, with a treatment period extending up to 61 days. The clinical product differs from the commercial product only in color and engraving, with the clinical version being green, plain, and diamond-shaped. Dapagliflozin is also of chemical origin and is produced by AstraZeneca AB.
The study employs a placebo control, referred to as **Baxdrostat placebo**. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know who is receiving the active treatment versus the placebo. The pharmaceutical form, dosage, and administration route for the placebo are not specified in the provided data. The placebo is intended to mimic the administration of Baxdrostat without containing the active substance.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the time to the first occurrence of any components of the composite endpoint, which includes a ≥ 50% sustained decline in estimated glomerular filtration rate (**eGFR**), onset of kidney failure, or cardiovascular (CV) death. Kidney failure is defined as sustained eGFR < 15 mL/min/1.73 m², chronic dialysis treatment, receiving a kidney transplant, or death with a renal primary cause.
Secondary endpoints include changes from baseline in urine albumin-to-creatinine ratio (UACR) and mean systolic blood pressure (SBP). Additionally, the time to the first occurrence of any components of another composite endpoint, which includes CV death, heart failure (HF) with and without hospitalization, myocardial infarction (MI), and stroke, will be evaluated. The occurrence of CV death and overall death will also be assessed as secondary endpoints.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent.
- Participants with (a) or (b): a) eGFR 30-59 mL/min/1.73 m² (local or central laboratory value) AND: - UACR ≥ 30 mg/g (3.39 mg/mmol) and < 500 mg/g (56.5 mg/mmol) (central laboratory value), or - UACR ≥ 500 mg/g (56.5 mg/mmol) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or - UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only). (b) eGFR 60-75 mL/min/1.73 m² (local or central laboratory value) AND: - UACR ≥ 500 mg/g (56.5 mg/mmol) ) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or - UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only)
- Participants with history of HTN and a SBP ≥ 130 mmHg (the most recent value within 4 weeks prior to screening or at Screening visit) and ≥ 120 mmHg at the randomisation visit
- Stable and maximum tolerated dose of an ACEi or an ARB (not both) for at least 4 weeks prior to Screening Visit.
- Participants with: a) Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values). b) Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR < 45 mL/min/1.73 m2 (local or central laboratory values).
Exclusion Criteria
- Systolic blood pressure > 180 mmHg, or diastolic BP > 110 mmHg at screening.
- Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.
- Serum sodium < 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit).
- Participants with T1DM will be excluded, except: a) For US only: patients with T1DM treated with SGLT2i for at least 4 months, without DKA during that period, and who have experience with ketone monitoring are eligible for inclusion. b)For Japan only: patients with T1DM treated with dapagliflozin 10 mg for at least 4 months, without DKA during the period of dapagliflozin treatment are eligible for inclusion.
- Uncontrolled T2DM with HbA1c > 10.5% (> 91 mmol/mol) (central or local laboratory values obtained within 3 months prior to screening or at the Screening Visit).
- New York Heart Association functional HF class IV at screening.
- Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation.
- Documented history of adrenal insufficiency.
- Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
- Any acute kidney injury within 3 months prior to the Screening Visit.
- History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
- Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to Visit 1).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 15 Apr 2025 | 82 |
 Bulgaria | Recruiting | 15 Apr 2025 | 122 |
 Czechia | Recruiting | 15 Apr 2025 | 51 |
 Denmark | Recruiting | 15 Apr 2025 | 32 |
 France | Recruiting | 15 Apr 2025 | 110 |
 Germany | Recruiting | 15 Apr 2025 | 125 |
 Greece | Recruiting | 15 Apr 2025 | 44 |
 Hungary | Recruiting | 15 Apr 2025 | 51 |
 Italy | Recruiting | 15 Apr 2025 | 85 |
 The Netherlands | Recruiting | 15 Apr 2025 | — |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Baxdrostat | Test | TABLET | ORAL | 00 | 60 | PRD10361088 |
Baxdrostat | Test | TABLET | ORAL | 00 | 60 | PRD10361078 |
Forxiga 10 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 10 | 61 | PRD8495988 |
Baxdrostat placebo | Placebo | N/A | — | — | — | N/A |
Baxdrostat | Test | TABLET | ORAL | 00 | 60 | PRD12913417 |