CTRI/2025/05/086224 [Registered on: 02/05/2025] Trial Registered Prospectively
Last Modified On:
08/08/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A trial to learn how safe baxdrostat with dapagliflozin is and how well it works in adults with chronic kidney disease (CKD) and high blood pressure
Scientific Title of Study
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).
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
D6972C00002 Protocol Version 2.0 dated 12 Nov 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dinesh Khullar
Designation
Chairman Nephrology & Renal Transplant Medicine
Affiliation
Max Super Speciality Hospital Saket
Address
A Unit of Max Healthcare Institute Limited,
1, Press Enclave Road, Saket, India
New Delhi DELHI 110017 India
Phone
981012066
Fax
Email
dinesh.khullar@maxhealthcare.com
Details of Contact Person Scientific Query
Name
Tapankumar M Shah
Designation
Senior Director, Cluster Head, SMM BioPharmaceuticals, R and D BioPharmaceuticals,
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road,
India
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Public Query
Name
Tapankumar M Shah
Designation
Senior Director, Cluster Head, SMM BioPharmaceuticals, R and D BioPharmaceuticals,
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road,
India
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB, 151 85 Södertälje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore - 560045,
Karnataka, India
Countries of Recruitment
Argentina Belgium Brazil Bulgaria Canada Chile China Colombia Czech Republic Denmark Egypt France Germany Greece Hungary India Israel Italy Japan Malaysia Mexico Netherlands Peru Philippines Poland Republic of Korea Romania Saudi Arabia Serbia Singapore Slovakia South Africa Spain Sweden Taiwan Thailand Turkey Ukraine United Kingdom United States of America Viet Nam Australia
Professor and HOD
Department of Nephrology
Nil Ratan Sircar Medical College and Hospital, 138, AJC Bose Road, PIN - 700014
Kolkata WEST BENGAL
9231078078
drpinaki71@yahoo.com
Dr Arunkumar Subbiah
All India Institute of Medical Sciences, Delhi
Associate Professor, Department of Nephrology, Room Number 03, porta cabin, 4th floor, teaching block, AIIMS, Ansari Nagar, PIN - 110029 New Delhi DELHI
9811196857
gmedaks@gmail.com
Dr Himansu Sekhar Mahapatra
Atal Bihari Vajpayee Institute of Medical Sciences, Dr. Ram Manohar Lohia Hospital,
Director, Professor and Head
Department of Nephrology Atal Bihari Vajpayee Institute of Medical Sciences, Dr. Ram Manohar Lohia Hospital, Baba Kahrak Singh Marg, Near Gurudwara Bangla Sahib, Connaught Place, PIN - 110001
New Delhi DELHI
9968474805
hsmnephro@gmail.com
Dr Ratan Jha
Care Hospitals
Senior Consultant
Department of Nephrology Care Hospitals, 6-3-248/2, Road no.1, Banjara Hills, PIN - 500034
Hyderabad TELANGANA
9848027683
jharatan08@gmail.com
Dr Anil Kumar B T
Gleneagles BGS Hospital, Bangalore
HOD and Senior Consultant
Department of Nephrology Gleneagles BGS Hospital, No 67, Uttarahali Main Road, Kengeri, PIN- 560060
Bangalore KARNATAKA
9916950554
anilbuskal@yahoo.co.in
Dr Nageswara Rao Cherukappalli
Government Siddhartha Medical College, Vijayawada
Assistant Professor, Department of Nephrology, Ring Road, Gunadala, Vijayawada, PIN -520008 Krishna ANDHRA PRADESH
9494475996
drcnr9@gmail.com
Dr Atanu Pal
Institute of Post-Graduate Medical Education & Research (IPGME&R and SSKM Hospital)
Assistant Professor, Department of Nephrology, 244, AJC Bose Road, PIN 700020 Kolkata WEST BENGAL
9848148967
drsaikrishnamaddi@gmail.com
Dr Madan M Bahadur
Jaslok Hospital and Research Centre
Director
Department of Nephrology
Jaslok Hospital and Research Centre, 15, Dr. G Deshmukh Marg, PIN- 400026
Mumbai MAHARASHTRA
9820183965
madan.bahadur@gmail.com
Dr Ritesh Ramesh Vernekar
KLES Dr Prabhakar Kore Hospital & Medical Research Centre
Department of Nephrology,
Nehrunagar, PIN- 590010, India Belgaum KARNATAKA
9449061633
riteshvernekar@gmail.com
Dr Dinesh Khullar
Max Super Speciality Hospital, Saket, Delhi
Chairman, Nephrology and Renal Transplant Medicine, Department of Nephrology, Saket (West block), A Unit of Max Healthcare Institute Limited), 1-Press Enclave Road, Saket, PIN - 110017 New Delhi DELHI
9810124066
drdineshkhullar@gmail.com
Dr Sampath Kumar Krishnaswamy
Meenakshi Mission Hospital and Research Centre
Senior Consultant and Head
Department of Nephrology
Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, PIN - 625107
Madurai TAMIL NADU
9994872250
drksampath@gmail.com
Dr D Sree Bhushan Raju
Nizams Institute of Medical Sciences
Senior Professor and Unit Head
Department of Nephrology
Nizams Institute of Medical Sciences, Panjagutta, PIN - 500082
Hyderabad TELANGANA
9030292929
sreebhushan@hotmail.com
Dr Avinash Ignatius
Noble Hospital Pvt. Ltd.
HOD and Senior Consultant
Department of Nephrology
Noble Hospital Pvt. Ltd., 1st Floor, Nephrology OPD, Noble Annex, 153 Magarpatta City Road, Hadapsar, PIN- 411013
Pune MAHARASHTRA
9823101982
dr_ignatius@yahoo.co.in
Dr M V S Krishna
Sunrise Hospitals
Chief Nephrologist Sunrise Hospitals Department of Nephrology Sunrise Hospitals ( A Unit of NH Healthcare Services Pvt Ltd), Opposite Corporation Bank, Bellapu Sobhanadri Road, Near Pushpa Hotel Centre, Suryaraopet, Ijayawada PIN - 520002 Krishna ANDHRA PRADESH
9848148967
drsaikrishnamaddi@gmail.com
Dr Anupam Agarwal
Vardhaman Mahavir Medical College and Safderjung Hospital,
Assistant Professor
Department of Nephrology Vardhaman Mahavir Medical College and Safderjung Hospital, 2nd Floor, Department of Nephrology, Ansari Nagar West, PIN - 110029
New Delhi DELHI
Dose: Baxdrostat 1 mg / 2 mg + Dapagliflozin 10 mg
Frequency : One tablet Bax/matching placebo and one tablet of Dapagliflozin once daily
Route of administration : oral tablet
Total duration of intervention: approx 41 months to 60 months depending on the occurrence of endpoint event (Renal composite: 50% sustained decline in eGFR, onset of kidney failure, CV death)
Comparator Agent
Placebo and dapagliflozin
Dose: Placebo 1 mg / 2 mg + Dapagliflozin 10 mg
Frequency : One tablet Bax/matching placebo and one tablet of Dapagliflozin once daily
Route of administration : oral tablet
Total duration of intervention: approx 41 months to 60 months depending on the occurrence of endpoint event (Renal composite: 50% sustained decline in eGFR, onset of kidney failure, CV death)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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:
1. 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.
2. 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
ExclusionCriteria
Details
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).
- T1DM:
- 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).
- Drug or alcohol abuse that in the Investigator s judgement makes the participant a poor candidate for the study.
Prior/Concomitant Therapy
- 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.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
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.
The number of events is estimated to occur in an average follow-up of approximately 41 months
Secondary Outcome
Outcome
TimePoints
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:
- CV death
- HF with and without hospitalisation
- MI
- Stroke
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.
Total Sample Size="5000" Sample Size from India="122" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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.