CTRI/2025/05/086224招募中3 期
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 (BaxDuo-Pacific).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 5,000
- 试验地点
- 15
- 主要终点
- To determine whether baxdrostat dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of greater than or equal 50 percent sustained decline in eGFR, kidney failure, or CV death.
研究概览
简要总结
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 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. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Demographic Characteristics Age.
- •Participants of any sex and gender must be 18 years of age at the time of signing the informed consent. Disease Characteristics.
- •Participants with a) eGFR greater than or equal to 30 and less than60 mL/min/1.73 m2 (local or central laboratory values), AND UACR greater than or equal to 30 mg/g (3.39 mg/mmol) and less than500 mg/g (56.5 mg/mmol) (central laboratory values only), or b) eGFR greater than or equal to 30 and lesser than or equal to 75 mL/min/1.73 m2 (local or central laboratory values), AND UACR greater than or equal to 500 mg/g (56.5 mg/mmol) and lesser than or equal to 5000 mg/g (565 mg/mmol) or UPCR greater than or equal to 700 mg/g (79 mg/mmol) and lesser than or equal to 7000 mg/g (790 mg/mmol) (local or central laboratory values).
- •Participants with history of HTN and a SBP greater than or equal to 130 mmHg (the most recent value within 4 weeks of screening or at the Screening Visit) and greater than or equal to 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 greater than or equal to 3.0 and lesser than or equal to 4.8 mmol/L if eGFR greater than or equal to 45 mL/min/1.73 m2 (local or central laboratory values) b) Serum or plasma potassium greater than or equal to 3.0 and lesser than or equal to 4.5 mmol/L if eGFR less than45 mL/min/1.73 m2 (local or central laboratory values) Results for eGFR, potassium, and sodium used for assessing inclusion/exclusion criteria should be obtained on the same day, should be the most recent values within 4 weeks of screening or at the Screening Visit, and should be either all local or all central laboratory values Sex and Contraceptive/Barrier Requirements.
- •Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Participants not of childbearing potential are defined as participants who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Participants will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
- •Participants who may become pregnant less than50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range. FSH can be based on local (within 3 months prior to screening or at the Screening Visit) or central laboratory values.
- •Participants who may become pregnant greater than or equal to 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
- •Participants of childbearing potential must use 1 highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1 percentage per year when used consistently and correctly. WOCBP who are sexually active with a nonsterilised male partner must agree to use 1 highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 4 weeks after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician.
- •The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, lactational amenorrhoea, female condom, and male condom.
- •Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) [(periodic abstinence eg, calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception], a vasectomised partner, Implanon, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, DepoProvera injections, oral contraceptive, and Evra Patch, Xulane or NuvaRing.
- •All WOCBP must have a negative pregnancy test result at Visit 1, and not be at the stage of breastfeeding. Informed Consent -Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Provision of signed and dated, written ICF prior to any study-specific procedures (pre-screening ICF and ICF collected at screening). Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of optional genetic samples for Genomics Initiative research that supports the Genomic Initiative.
排除标准
- •Participants are excluded from the study if any of the following criteria apply: Medical Conditions.
- •Systolic blood pressure greater than 180 mmHg, or diastolic BP greater than 110 mmHg at screening.
- •Known hyperkalaemia, defined as potassium of greater than or equal to 5.5 mmol/L within 3 months prior to screening.
- •Serum sodium less than 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit).
- •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.
- •Uncontrolled T2DM with HbA1c greater than 10.5 percentage (greater than 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 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 Screening Visit.
- •Any acute kidney injury within 3 months prior to the Screening Visit.
- •Known hypersensitivity to the study treatment (active substance or excipients).
- •History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
- •History or ongoing allergy/hypersensitivity, as judged by the Investigator, to SGLT2i (eg, empagliflozin) or ASI.
- •Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to Visit 1).
- •Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), ASI, or potassium-sparing diuretics (such as triamterene or amiloride) within 4 weeks prior to screening.
- •Concomitant therapy with strong inducers of CYP450 3 A (eg, apalutamide, avasimibe, carbamazepine, enzalutamide, lumacaftor, mitotane, phenytoin, rifampin, rifapentine, St John s wort). Other Exclusions.
- •Any use of potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening. However, their use is allowed after randomisation based on the Investigator and treating physician s judgement.
- •Any other condition or therapy, in the judgement of the Investigator or AstraZeneca, which would make the participant unsuitable for this study, including a condition or therapy which the Investigator anticipates will not allow participation for the full planned study period (eg, active malignancy or other condition limiting life expectancy to less than 12 months).
- •Participation in another clinical study with a study intervention administered in the last 3 months prior to randomisation.
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or site personnel).
- •For WOCBP, positive pregnancy test and/or being breastfeeding.
结局指标
主要结局
To determine whether baxdrostat dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of greater than or equal 50 percent sustained decline in eGFR, kidney failure, or CV death.
时间窗: The number of events is estimated to occur in an average follow-up of approximately 41 months
次要结局
- To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing UACR.(Change from baseline in UACR at 16 weeks)
- To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing SBP.(Change from baseline in mean SBP at 16 weeks)
- To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of MACE (CV death, HF events, MI, stroke).(Time to the first occurrence of any of the components of the composite of:)
- To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of CV death.(Time to CV death)
- To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of all-cause death.(Time to death)
研究者
Dr Dinesh Khullar
Max Super Speciality Hospital Saket
研究点 (15)
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