A Phase Iii, Randomised, Double-Blind, Placebo-Controlled, Event-Driven Study to Assess the Efficacy, Safety and Tolerability of Baxdrostat in Combination With Dapagliflozin Compared With Dapagliflozin Alone on Renal Outcomes and Cardiovascular Mortality in Participants With Chronic Kidney Disease and High Blood Pressure
Investigational Medication for Chronic Kidney Disease and High Blood Pressure
Sharon Moe, MD
Primary Investigator
Brief description of study
The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN.
THIS STUDY IS ENROLLING BY INVITATION ONLY
Detailed description of study
This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin.
Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months.
The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor.
In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Chronic Kidney Disease, CKD, Hypertension, High blood pressure
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Age: 18 years - 100 years
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Gender: All
Inclusion Criteria:
- Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent.
- Participants with:
- eGFR ≥ 30 and < 60 mL/min/1.73 m2 (local or central laboratory values) AND UACR ≥ 30 mg/g (3.39 mg/mmol) and < 500 mg/g (56.5 mg/mmol) (central laboratory values only), or
- eGFR ≥ 30 and ≤ 75 mL/min/1.73 m2 (local or central laboratory values) AND UACR ≥ 500 mg/g (56.5 mg/mmol) and ≤ 5000 mg/g (565 mg/mmol) or UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local or central laboratory values).
- [obsolete]
- Participants with history of HTN and a SBP ≥ 130 mmHg (the most recent value within 4 weeks prior to screening or at the 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:
- Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values).
- 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 prior to screening.
- Serum sodium < 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit).
4. T1DM:
- 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.
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.
5 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).
6 New York Heart Association functional HF class IV at screening.
7 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.
8 Documented history of adrenal insufficiency.
9 Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
10 Any acute kidney injury within 3 months prior to the Screening Visit.
11 History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
12 Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to Visit 1).
This study investigates how well an investigational medication works when combined with another medicine in people with chronic kidney disease (CKD) and high blood pressure (hypertension). CKD is a condition where the kidneys are damaged and can't filter blood as well as they should. Hypertension is when the blood pressure in the arteries is higher than it should be. The purpose of this study is to see if the investigational medication can help reduce kidney problems and heart-related deaths compared to using the other medicine alone.
Participants in the study will be randomly assigned to receive either the investigational medication with another medicine or a placebo with the other medicine. A placebo is an inactive substance that looks like the investigational medicine but does not contain any medicine. The study includes a period where participants will take only the other medicine to prepare for the main study phase. During the study, participants will have regular visits to check their health and collect data.
- Who can participate: Adults aged 18 and older with chronic kidney disease and high blood pressure are eligible. Key criteria include specific kidney function levels and blood pressure measurements, as well as stability on certain medications.
- Study details: Participants will take either the investigational medication with another medicine or a placebo with the other medicine. They will continue their regular visits and data collection even if they stop the study medication early.
- Study visits: The study requires 6 visits.
