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.

Официальное название

A Phase IIb, Randomised, Multicentre, Double-Blind Study to Evaluate the Effect of Baxdrostat in Combination With Dapagliflozin Compared With Baxdrostat on Albuminuria in Participants With Chronic Kidney Disease and High Blood Pressure.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Baxdrostat/dapagliflozin
  baxdrostat tablet dapagliflozin tablet
• Препарат Baxdrostat/Placebo
  baxdrostat tablet placebo tablet

Первичные конечные точки

• To determine whether baxdrostat/dapagliflozin is superior to baxdrostat/matching placebo at reducing albuminuria. [Срок оценки: Up to 12 weeks]

Критерии участия

Критерии включения

• 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 < 90 mL/min/1.73 m2 at screening
• Participants with UACR > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening
• Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit.
• 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.
• Participants with:

• Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2.
• Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR < 45 mL/min/1.73 m2.
• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Applicable to female participants.

Критерии исключения

• Systolic blood pressure > 180 mmHg, or diastolic blood pressure > 110 mmHg at screening.
• Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months before screening
• Serum sodium < 135 mmol/L at the Screening Visit (values obtained within 4 weeks prior to screening or at the Screening Visit).
• Diabetes mellitus:

• T1DM at the screening visit
• Uncontrolled T2DM at screening: HbA1C > 10.5% (> 91 mmol/mol)
• New York Heart Association functional HF class IV at screening
• 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
• 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.
• Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history.
• Documented history of adrenal insufficiency.
• Any dialysis (including for acute kidney injury) within 3 months prior to the screening
• Any acute kidney injury within 3 months prior to the screening visit.
• Prohibited concomitant medications

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 18 центров

• Research Site — Surprise
• Research Site — Hollywood
• Research Site — Port Charlotte
• Research Site — Port Orange
• Research Site — Atlanta
• Research Site — Champaign
• Research Site — Wichita
• Research Site — Eatontown
• … и ещё 10 центров

Тайвань · 8 центров

• Research Site — Kaohsiung City
• Research Site — Kaohsiung City
• Research Site — New Taipei City
• Research Site — Taichung
• Research Site — Taichung
• Research Site — Taipei
• Research Site — Taipei
• Research Site — Taoyuan

Украина · 8 центров

• Research Site — Kyiv
• Research Site — Kyiv
• Research Site — Kyiv
• Research Site — Kyiv
• Research Site — Kyiv
• Research Site — Kyiv
• Research Site — Uzhhorod
• Research Site — Vinnytsia

Болгария · 7 центров

• Research Site — Pernik
• Research Site — Plovdiv
• Research Site — Sofia
• Research Site — Sofia
• Research Site — Sofia
• Research Site — Sofia
• Research Site — Yambol

Аргентина · 5 центров

• Research Site — Buenos Aires
• Research Site — Ciudad de Buenos Aires
• Research Site — Mar del Plata
• Research Site — Rosario
• Research Site — San Nicolás

Канада · 5 центров

• Research Site — Courtice
• Research Site — Etobicoke
• Research Site — Stouffville
• Research Site — Waterloo
• Research Site — Montreal

Таиланд · 5 центров

• Research Site — Bangkoknoi
• Research Site — Changwat Sara Buri
• Research Site — Hat Yai
• Research Site — Muang
• Research Site — Ratchathewi

Turkey (Türkiye) · 5 центров

• Research Site — Adana
• Research Site — Adapazarı
• Research Site — Kahramanmaraş
• Research Site — Kayseri
• Research Site — Kocaeli

South Korea · 4 центра

• Research Site — Anyang-si
• Research Site — Cheonan-si
• Research Site — Goyang-si
• Research Site — Seoul

Испания · 3 центра

• Research Site — Badalona
• Research Site — Pamplona
• Research Site — Valencia

Великобритания · 3 центра

• Research Site — Dundee
• Research Site — Liverpool
• Research Site — London

Идентификаторы

NCT: NCT07222917 · D6972C00006

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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