A Phase IIb Study to Evaluate the Effect of Dapagliflozin in Combination With Baxdrostat Compared With Baxdrostat on Albuminuria in Participants With Chronic Kidney Disease and High Blood Pressure.
Purpose
International, Multicenter and Double-Blind study. The purpose is to measure the effect of baxdrostat in combination with dapagliflozin compared with baxdrostat/placebo on albuminuria, as well as safety, in participants with chronic kidney disease and high blood pressure.
Condition
- Chronic Kidney Disease and Hypertension
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent. 2. Participants with eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening 3. Participants with UACR > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening 4. Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit. 5. Stable and maximum daily tolerated dose of either an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to the screening visit, if not medically contraindicated. 6. Participants with: 1. Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2. 2. Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR < 45 mL/min/1.73 m2. 7. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Applicable to female participants.
Exclusion Criteria
- Systolic blood pressure > 180 mmHg, or diastolic blood pressure > 110 mmHg at screening. 2. Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months before screening 3. Serum sodium < 135 mmol/L at the Screening Visit (values obtained within 4 weeks prior to screening or at the Screening Visit). 4. Diabetes mellitus: 1. T1DM at the screening visit 2. Uncontrolled T2DM at screening: HbA1C > 10.5% (> 91 mmol/mol) 5. New York Heart Association functional HF class IV at screening 6. Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), aldosterone synthase inhibitors, potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening 7. Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening HF within previous 3 months prior to randomisation. 8. Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history. 9. Documented history of adrenal insufficiency. 10. Any dialysis (including for acute kidney injury) within 3 months prior to the screening 11. Any acute kidney injury within 3 months prior to the screening visit. 12. Prohibited concomitant medications
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Interventional, multicentre, randomised, double-blind, parallel group
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- The IRT/RTSM will provide to the Investigator(s) or pharmacist(s) the kit identification number to be allocated to the participant at the dispensing visit. The following personnel will be unblinded: - Personnel carrying out the packaging and labelling of study intervention treatment - Personnel generating the randomisation list Participants, site personnel, and AstraZeneca will be blinded to study intervention. AstraZeneca retains the right to break the code for SAEs that are unexpected and are suspected to be causally related to study intervention and that potentially require expedited reporting to regulatory authorities. Randomisation codes will not be broken for the planned analyses of data until all decisions on the evaluability of the data from each individual participant have been made and documented.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Baxdrostat/dapagliflozin |
Participants randomised to the baxdrostat/dapagliflozin arm will receive one dose of baxdrostat and one standard dose of dapagliflozin daily. |
|
|
Placebo Comparator Baxdrostat /placebo |
Patients will receive one dose of baxdrostat comparator in combination with placebo matching dapagliflozin daily |
|
Recruiting Locations
Surprise, Arizona 85374
Hollywood, Florida 33021
Port Charlotte, Florida 33952
Port Orange, Florida 32127
Atlanta, Georgia 30344
Champaign, Illinois 61822
Wichita, Kansas 67214
Eatontown, New Jersey 07724
Greenville, North Carolina 27834
Jacksonville, North Carolina 28546
New Bern, North Carolina 28562
Columbus, Ohio 43215
Media, Pennsylvania 19063
East Providence, Rhode Island 02914
Arlington, Texas 76015
Pasadena, Texas 77504
San Antonio, Texas 78212
Woodbridge, Virginia 22192
More Details
- NCT ID
- NCT07222917
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
Detailed Description
This is a Phase IIb, randomised, multicentre, double-blind, parallel-group study aiming to determine the effect on albuminuria, as well as safety, of baxdrostat/dapagliflozin compared with baxdrostat/placebo, when given to participants with CKD and high blood pressure. Study population will include participants ≥ 18 years old with CKD. Participants with or without a diagnosis of T2DM and with or without an SGLT2i treatment at screening are eligible for the study. The study will include an optional pre-screening period, where participants will be assessed for at least one of the following parameters: eGFR, UACR, potassium, sodium, and BP. Participants who are being treated with SGLT2i at the time of the screening visit will complete a washout period After screening and initial confirmation of eligibility, participants will be randomised to receive either baxdrostat/dapagliflozin or baxdrostat/placebo. For randomisation there will be stratification and capping linked to T2DM status. The primary objective is to assess the effect of baxdrostat/dapagliflozin compared with baxdrostat/matching placebo on albuminuria, which will be evaluated by change from baseline in UACR. The end of the study is defined as the date of the last visit of the last participant in the study or last scheduled procedure shown in the SoA for the last participant in the study globally, whichever occurs last. A participant is considered to have completed the study if they have completed all periods of the study including the last scheduled procedure shown in the SoA.