Clinical trial • Phase III • Cardiology|Nephrology
BAXDROSTAT for Chronic kidney disease | Hypertension
Phase III trial of BAXDROSTAT for Chronic kidney disease | Hypertension.
Overview
- Trial Therapeutic Area
- Cardiology|Nephrology
- Trial Disease
- Chronic kidney disease | Hypertension
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 31-01-2024
- First CTIS Authorization Date
- 22-05-2024
Trial design
Randomised, baxdrostat in combination with dapagliflozin compared with dapagliflozin alone (placebo/dapagliflozin). dapagliflozin (forxiga) 10 mg oral daily is specified; baxdrostat oral tablet (dose not specified in part i product entry). baxdrostat placebo used for blinding.-controlled Phase III trial in France, Poland, Italy and others.
- Randomised
- Yes
- Comparator
- Baxdrostat in combination with dapagliflozin compared with dapagliflozin alone (placebo/dapagliflozin). Dapagliflozin (Forxiga) 10 mg oral daily is specified; Baxdrostat oral tablet (dose not specified in Part I product entry). Baxdrostat placebo used for blinding.
- Target Sample Size
- 1825
Eligibility
Recruits 1825 Vulnerable population is selected in the application. Only adults (≥18 years) are eligible. Country- and language-specific subject information sheets and informed consent forms are provided (including optional genomics consent and addenda for handling personal data); separate materials for pregnant subjects are available. Informed consent is provided by the participant (no assent for minors, as minors are excluded)..
- Vulnerable Population
- Vulnerable population is selected in the application. Only adults (≥18 years) are eligible. Country- and language-specific subject information sheets and informed consent forms are provided (including optional genomics consent and addenda for handling personal data); separate materials for pregnant subjects are available. Informed consent is provided by the participant (no assent for minors, as minors are excluded).
Inclusion criteria
- {"criterion_text":"- Participants of any sex and gender must be ≥ 18 years old, or older, at the time of signing the informed consent."}
- {"criterion_text":"- Participants with CKD and eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening"}
- {"criterion_text":"- Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening"}
- {"criterion_text":"- Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit"}
- {"criterion_text":"- Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit"}
- {"criterion_text":"- 6. Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR: o for participants with screening eGFR ≥ 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.8 mmol/L at the Screening Visit o for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.5 mmol/L at the Screening Visit"}
Exclusion criteria
- {"criterion_text":"- Medical Conditions 1. Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening."}
- {"criterion_text":"- History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI."}
- {"criterion_text":"- Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1."}
- {"criterion_text":"- Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), 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."}
- {"criterion_text":"- Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening."}
- {"criterion_text":"- Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory."}
- {"criterion_text":"- Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus with HbA1c > 10.5% (> 91 mmol/mol) at Screening."}
- {"criterion_text":"- New York Heart Association functional HF class IV at screening."}
- {"criterion_text":"- 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."}
- {"criterion_text":"- Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit."}
- {"criterion_text":"- Any acute kidney injury within 3 months prior to the Screening Visit"}
- {"criterion_text":"- History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant)."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Change from baseline in eGFR to post treatment.","definition_or_measurement_approach":"Assessed as change in eGFR (estimated glomerular filtration rate) over time (effect on change in eGFR over time)."}
Secondary endpoints
- {"endpoint_text":"- 1. Change from baseline in UACR.","definition_or_measurement_approach":"Change from baseline in urine albumin-creatinine ratio (UACR)."}
- {"endpoint_text":"- 2. Change from baseline in systolic BP (blood pressure).","definition_or_measurement_approach":"Change from baseline in systolic blood pressure (SBP)."}
- {"endpoint_text":"- 3. Kidney hierarchical composite endpoint.* *Defined as the most severe outcome of the following: 1. Death; 2. KFRT (chronic dialysis or kidney transplant); 3. Sustained GFR < 15 mL/min/1.73 m2; 4. Sustained GFR decline from baseline of ≥ 57%; 5 Sustained GFR decline from baseline of ≥ 50%; or 6. individual change from baseline to post-treatment eGFR if none of the outcomes occurred.","definition_or_measurement_approach":"Hierarchical composite renal endpoint defined as the most severe outcome in the ordered list (death; KFRT; sustained GFR <15; sustained GFR decline ≥57%; sustained GFR decline ≥50%; or individual change in eGFR if none occurred)."}
- {"endpoint_text":"- 4. Change in eGFR from following randomisation.","definition_or_measurement_approach":"Change in eGFR measured after randomisation vs baseline."}
- {"endpoint_text":"- 5. Time to the first occurrence of any of the components of the composite of: 1) CV death 2) HF with and without hospitalisation 3) MI 4) Stroke","definition_or_measurement_approach":"Time-to-event for first occurrence of composite cardiovascular outcomes (MACE components: CV death, heart failure with/without hospitalisation, myocardial infarction, stroke)."}
Recruitment
- Digital Remote Recruitment
- True, documented methods include online landing pages, web recruitment, prescreening questionnaires, use of databases and SMS for outreach (country-specific recruitment materials reference web/landing page, database, Pratia web, and SMS approaches).
- Planned Sample Size
- 1825
- Recruitment Window Months
- 47
- Consent Approach
- Informed consent is obtained from adult participants (≥18) using country- and language-specific subject information sheets and informed consent forms. Multiple ICF versions and addenda exist (including optional genomics consent, addenda for handling personal data, and separate materials for pregnant subjects). Documents available in multiple languages according to country (examples in repository: French, English, Spanish, Italian, Czech, Hungarian, Polish, Swedish, Romanian, Greek, Bulgarian, Dutch, etc.).
Methods
- Posters and pamphlets (site-level K2 recruitment materials documented for multiple countries).
- Patient letters and printed pamphlets (country-specific K2 materials).
- Scripts for recruitment videos and site videos (documented).
- Digital recruitment: online landing pages, study web pages, web prescreening questionnaires, databases and web-based recruitment (documents reference vendor materials such as Pratia web/landing page/database and SMS approaches).
Geography
- Total Number Of Participants
- 1825
France
- Earliest CTIS Part Ii Submission Date
- 22-03-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 62
- Number Of Participants
- 50
Poland
- Earliest CTIS Part Ii Submission Date
- 25-04-2024
- Latest Decision Or Authorization Date
- 27-05-2024
- Processing Time Days
- 32
- Number Of Participants
- 50
Italy
- Earliest CTIS Part Ii Submission Date
- 20-02-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 93
- Number Of Participants
- 30
Sweden
- Earliest CTIS Part Ii Submission Date
- 26-04-2024
- Latest Decision Or Authorization Date
- 27-05-2024
- Processing Time Days
- 31
- Number Of Participants
- 35
Hungary
- Earliest CTIS Part Ii Submission Date
- 20-03-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 64
- Number Of Participants
- 35
Romania
- Earliest CTIS Part Ii Submission Date
- 26-04-2024
- Latest Decision Or Authorization Date
- 27-05-2024
- Processing Time Days
- 31
- Number Of Participants
- 60
Denmark
- Earliest CTIS Part Ii Submission Date
- 29-04-2024
- Latest Decision Or Authorization Date
- 22-05-2024
- Processing Time Days
- 23
- Number Of Participants
- 30
Spain
- Earliest CTIS Part Ii Submission Date
- 19-04-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 34
- Number Of Participants
- 45
Czechia
- Earliest CTIS Part Ii Submission Date
- 26-04-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 27
- Number Of Participants
- 55
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 20-05-2024
- Latest Decision Or Authorization Date
- 28-05-2024
- Processing Time Days
- 8
- Number Of Participants
- 70
Netherlands
- Earliest CTIS Part Ii Submission Date
- 15-05-2024
- Latest Decision Or Authorization Date
- 27-05-2024
- Processing Time Days
- 12
- Number Of Participants
- 30
Germany
- Earliest CTIS Part Ii Submission Date
- 26-04-2024
- Latest Decision Or Authorization Date
- 22-05-2024
- Processing Time Days
- 26
- Number Of Participants
- 60
Greece
- Earliest CTIS Part Ii Submission Date
- 26-04-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 27
- Number Of Participants
- 35
Slovakia
- Earliest CTIS Part Ii Submission Date
- 19-04-2024
- Latest Decision Or Authorization Date
- 24-05-2024
- Processing Time Days
- 35
- Number Of Participants
- 50
Belgium
- Earliest CTIS Part Ii Submission Date
- 23-04-2024
- Latest Decision Or Authorization Date
- 23-05-2024
- Processing Time Days
- 30
- Number Of Participants
- 40
Sponsor
Primary sponsor
- Full Name
- Astrazeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- Baxdrostat
- Active Substance
- BAXDROSTAT
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL
- Authorisation Status
- Investigational (no marketing authorisation listed in Part I product entry)
- Investigational Product Name
- Forxiga 10 mg film-coated tablets
- Active Substance
- DAPAGLIFLOZIN
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL
- Authorisation Status
- Marketing authorisation (EU) – marketing authorisation number EU/1/12/795/011
- Starting Dose
- 10 mg
- Dose Levels
- 10 mg (documented clinical product max daily dose amount 10 mg)
- Frequency
- Daily
- Maximum Dose
- 10 mg daily
- Investigational Product Name
- Baxdrostat placebo
- Modality
- Other
- Authorisation Status
- Placebo (not applicable)
- Combination Treatment
- Yes
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