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Purpose

International, Multicenter, Double-Blind, Placebo-Controlled and Event-driven study to assess efficacy, safety and Tolerability of Baxdrostat in combination with Dapagliflozin on renal outcomes and cardiovascular mortality in participants with chronic kidney disease and high blood pressure

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent. 2. 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 only), 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) 3. [obsolete] 4. 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. 5. Stable and maximum tolerated dose of an ACEi or an ARB (not both) for at least 4 weeks prior to Screening Visit. 6. Participants with: 1. Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values) 2. 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

  1. Systolic blood pressure > 180 mmHg, or diastolic BP > 110 mmHg at screening. 2. Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening. 3. Serum sodium < 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit). 4. Participants with T1DM will be excluded, except: 1. 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. 2. 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).

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
International, multi-centre, randomised, double-blind, parallel-group, placebo-controlled, event-driven, outcome
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Placebo controlled

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Baxdrostat/dapagliflozin 		Participants randomised to the baxdrostat/dapagliflozin arm will initially receive a lower dose of baxdrostat and standard dose dapagliflozin. For participants that meet the up-titration criteria, baxdrostat may be up-titrated to higher dose.
  • Drug: Baxdrostat/dapagliflozin
    baxdrostat tablet dapagliflozin tablet
    Other names:
    • Baxdrostat CIN-107
Placebo Comparator
Placebo/dapagliflozin 		Patients will receive one dose of dapagliflozin comparator in combination with matching placebo daily.
  • Drug: Placebo/dapagliflozin
    dapagliflozin tablet placebo tablet

Recruiting Locations

Research Site
Fairhope, Alabama 36532

Research Site
Surprise, Arizona 85374

Research Site
Tucson, Arizona 85710

Research Site
Beverly Hills, California 90211

Research Site
Concord, California 94520

Research Site
Fremont, California 94538

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Fullerton, California 92835

Research Site
Los Alamitos, California 90720

Research Site
Los Angeles, California 90073

Research Site
Stanford, California 94305

Research Site
Tarzana, California 91356

Research Site
Arvada, Colorado 80002

Research Site
New Britain, Connecticut 06051

Research Site
Washington D.C., District of Columbia 20037

Research Site
Boca Raton, Florida 33487

Research Site
Boynton Beach, Florida 33435

Research Site
Edgewater, Florida 32132

Research Site
Fort Lauderdale, Florida 33316

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Hollywood, Florida 33021

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Jacksonville Beach, Florida 32250

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Lake City, Florida 32055

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Lakeland, Florida 33805

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Melbourne, Florida 32901

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Ocoee, Florida 34761

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Port Charlotte, Florida 33952

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Port Orange, Florida 32127

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Riverview, Florida 33578

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Atlanta, Georgia 30328

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Atlanta, Georgia 30344

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Austell, Georgia 30106

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Brunswick, Georgia 31520

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Conyers, Georgia 30094

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Decatur, Georgia 30030

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Lawrenceville, Georgia 30046

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Riverdale, Georgia 30274

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Champaign, Illinois 61822

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Maywood, Illinois 60153

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Rockford, Illinois 61107

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Indianapolis, Indiana 46202

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Iowa City, Iowa 52242

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West Des Moines, Iowa 50266

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Hutchinson, Kansas 67502

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Kansas City, Kansas 66112

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Wichita, Kansas 67214

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Metairie, Louisiana 70006

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West Monroe, Louisiana 71291

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Bethesda, Maryland 20889

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Boston, Massachusetts 02115

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New Bedford, Massachusetts 02740

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Worcester, Massachusetts 01608

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Ann Arbor, Michigan 48109

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Detroit, Michigan 48202

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Garden City, Michigan 48135

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Saint Joseph, Michigan 49085

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Kansas City, Missouri 64111

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Kansas City, Missouri 64151

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St Louis, Missouri 63136

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Norfolk, Nebraska 68701

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Eatontown, New Jersey 07724

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Albany, New York 12205

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Buffalo, New York 14203

Research Site
New York, New York 10016

Research Site
Greenville, North Carolina 27834

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Hickory, North Carolina 28601

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Jacksonville, North Carolina 28546

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Kinston, North Carolina 28504

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Morehead City, North Carolina 28557

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New Bern, North Carolina 28562

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Raleigh, North Carolina 27609

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Rocky Mount, North Carolina 27804

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Sanford, North Carolina 27330

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Statesville, North Carolina 28625

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Wilmington, North Carolina 28401

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Wilmington, North Carolina 28412

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Winston-Salem, North Carolina 27103

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Canton, Ohio 44718

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Cincinnati, Ohio 45212

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Cincinnati, Ohio 45219

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Columbus, Ohio 43210

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Columbus, Ohio 43213

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Columbus, Ohio 43215

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Bridgeville, Pennsylvania 15017

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Butler, Pennsylvania 16001

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Exton, Pennsylvania 19341

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Media, Pennsylvania 19063

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East Providence, Rhode Island 02914

Research Site
East Providence, Rhode Island 02915

Research Site
Charleston, South Carolina 29414

Research Site
Columbia, South Carolina 29203

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Chattanooga, Tennessee 37421

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Knoxville, Tennessee 37912

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Knoxville, Tennessee 37938

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Nashville, Tennessee 37232

Research Site
Arlington, Texas 76015

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Austin, Texas 78726

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Austin, Texas 78735

Research Site
Austin, Texas 78751

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Dallas, Texas 75234

Research Site
Dallas, Texas 75246

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Houston, Texas 77004

Research Site
Houston, Texas 77099

Research Site
Humble, Texas 77346

Research Site
Pasadena, Texas 77504

Research Site
San Antonio, Texas 78212

Research Site
South Salt Lake, Utah 84115

Research Site
Burlington, Vermont 05401

Research Site
Arlington, Virginia 22205

Research Site
Manassas, Virginia 20110

Research Site
Newport News, Virginia 23606

Research Site
Woodbridge, Virginia 22192

Research Site
Seattle, Washington 98195

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

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 endpoint of ≥ 50% sustained decline in eGFR, kidney failure, HF events, or CV death in participants with CKD and HTN. 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 (N = 845) ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within 6 weeks of the PACD. This period can be extended by AstraZeneca. 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. Baxdrostat/placebo should not be administered without dapagliflozin: baxdrostat/placebo should be interrupted if dapagliflozin is interrupted (baxdrostat/placebo may be resumed with dapagliflozin, if dapagliflozin is resumed), and should be permanently discontinued if dapagliflozin is permanently discontinued. 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.