Finerenone for Patients With Primary Aldosteronism (FAIRY): A Multicenter, Randomized Clinical Trial
Phase: PHASE4
Conditions: Primary Aldosteronism
Sponsor: Qifu Li

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CLINICAL STUDY PROTOCOL 
 
Finerenone for Patients with Primary Aldosteronism 
(FAIRY): A Multicenter, Randomized, Clinical Trial 
 
 
 
 
 
 
 
 
Version Number: 1.0 
Date: May 08, 2024 
 
 
 
 
 
 

2 
 
Synopsis 
Title:  
Finerenone for Patients with Primary Aldosteronism (FAIRY): A Multicenter, 
Randomized, Clinical Trial. 
1.Objectives： 
1.1 The primary objective is to evaluate the antihypertensive efficacy of finerenone 
compared to spironolactone in patients with PA after 12 weeks of treatment. 
1.2 The secondary objective will include the followings:  
1) To evaluate efficacy on hypokalemia of finerenone compared to spironolactone in 
patients with PA after 12 weeks of treatment. 
2) To evaluate efficacy on plasma renin of finerenone compared to spironolactone in 
patients with PA after 12 weeks of treatment. 
3) To evaluate safety of finerenone compared to spironolactone in patients with PA 
after 12 weeks of treatment. 
 
2. Efficacy Endpoints: 
2.1 The primary efficacy endpoint  
The change from baseline in 24-hour systolic blood pressure (SBP) assessed by 24-hour 
ABPM compared to spironolactone after 12 weeks of finerenone therapy in patients 
with PA. 
 
2.2 The secondary efficacy endpoints 
The secondary efficacy endpoints include the followings: 
 
Change from baseline in 24-hour diastolic blood pressure (DBP) assessed by 24-
hour ABPM; 
 
Blood pressure control rate at the end of the study; 
Note: Blood pressure control rate is defined as the percentage of patients with mean 
seated office BP<140/90 mmHg. 
 
Change from baseline in daytime SBP assessed by 24-hour ABPM; 
 
Change from baseline in daytime DBP assessed by 24-hour ABPM; 
 
Change from baseline in nighttime SBP assessed by 24-hour ABPM; 
 
Change from baseline in nighttime DBP assessed by 24-hour ABPM; 
 
Change from baseline in office SBP;  
 
Change from baseline in office DBP; 
 
Change from baseline in serum potassium; 
 
Hypokalemia control rate at the end of the study 

3 
 
Note: Hypokalemia control rate is defined as the percentage of hypokalemic patients 
with serum potassium>3.5mmol/l at the end of the study. 
 
Change from baseline in plasma renin 
 
2.3 The exploratory endpoints  
The exploratory endpoints will include the followings: 
 
Change from baseline in urinary albumin-to-creatinine ratio (UACR);  
 
Change in the UACR in patients with baseline UACR more than 30 (mg/g Cr). 
 
2.4 The safety endpoints 
The safety endpoints will include the followings: 
 
Proportion of subjects with AEs; 
 
SAEs and AEs leading to discontinuation of treatment with study drug; 
 
Change in eGFR from baseline 
 
3.Population: 
3.1 Inclusion Criteria 
Patients who meet all of the following criteria will be eligible to participate: 
 
Aged between 18-75, male or female; 
 
With confirmed PA diagnosis (screening positive and at least one confirmatory test 
is positive); 
NOTE: Screening positive is defined as plasma aldosterone-to-renin ratio (ARR)≥ 
20(pg/ml)/(μIU/ml) or ARRing positive is defined as plasma aldosteroconcentration 
(PAC) post captopril challenge test (CCT) ≥ 110 pg/ml or PAC post seated saline 
infusion test (SSIT) ≥ 80 pg/ml is considered positive. [ARR≥10(pg/ml)/(μIU/ml) or 
ARR≥150(pg/ml)/(ng/ml/hr) can be considered positive if the patients with hypokalemia 
(serum potassium < 3.5mmol/L) or adrenal nodules (diameter > 1cm)]. 
 
Not taking any antihypertensive drugs or on a stable regimen of antihypertensive 
agents (only α receptor blockers, dihydropyridines or non dihydropyridines 
calcium channel blockers are allowed) for more than four weeks before screening; 
 
With a mean seated office SBP ≥ 140 or DBP ≥ 90 mmHg; 
 
Able and willing to give informed consent for participation in the clinical study. 
 
3.2 Exclusion Criteria 
1) Planning to have subtyping examinations of PA (eg. adrenal vein sampling, PET-
CT) within 3 months; 
2) 
Planning to have adrenal surgery or other surgery within 3 months 

4 
 
3) 
With a mean seated office SBP ≥ 180mmHg or DBP ≥ 110mmHg before 
randomization; 
Note: Mean seated BP is defined as the average of three seated BP measurements at 
any single clinical site visit. If the patient did not take their regularly scheduled 
antihypertensive medications prior to the visit, one BP re-test is allowed within two 
days after taking the medications. 
4) Night shift worker; 
5) Has a body mass index (BMI) ≥ 30 kg/m2 at screening; 
6) Has uncontrolled diabetes with fasting blood glucose (FBG) ≥13.3mmol/L at 
screening; 
7) Has uncontrolled chronic diseases; 
8) Has other known secondary hypertension (eg, renal artery stenosis, Cushing's 
syndrome, pheochromocytoma, or aortic coarctation); 
9) Has known and documented heart failure (New York Heart Association [NYHA] 
class III or IV), liver transaminase levels are more than twice the upper limit of 
normal; 
10) Has had CABG other major cardiac surgery (eg, valve replacement), peripheral 
arterial bypass surgery, or PCI within 6 months before screening; 
11) Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute 
coronary syndrome, or hospitalization for heart failure within 6 months before 
screening; 
12) Has poor compliance that can not fully participate in the study; 
13) Has hyperkalemia with serum potassium > 5.0mmol/L without potassium 
supplementation; 
14) Has a history of uncontrolled malignant tumor;  
15) The office blood pressure measurements difference of more than 20mmHg in both 
arms 
16) Unwilling or unable to stop taking medications might influence blood pressure, 
including sex hormones, glucocorticoids, non-steroidal anti-inflammatory drugs, 
cyclosporine, tacrolimus, or antidepressants; 
17) Is pregnant, breastfeeding, or planning to become pregnant during the study; 
18) Complicated with severe mental illness; 
19) Has had prior organ transplant; 
20) Has a history of allergy to finerenone or spironolactone; 
21) Has typical consumption of ≥ 15 alcoholic drinks weekly; 
Note: 1 drink of alcohol is equivalent to 360ml beer, 45ml spirits, or 150ml wine 
22) Has participated in another clinical study involving any investigational drug within 

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30 days prior to screening； 
23) Female of childbearing potential refusing to use non-hormonal methods of 
contraception during the study period; 
24) Refuse to get rid of grapefruit or grapefruit juice while receiving finerenone 
treatment; 
25) Other situations that the investigator assesses the subject as unable to complete the 
trial. 
 
3.Study Design and Duration 
3.1 Study Summery 
The study is a multicenter, randomized controlled trial. The First Affiliated Hospital of 
Chongqing Medical University will be the responsible unit, and the Affiliated Hospital 
of Southwest Medical University, the Third Xiangya Hospital of Central South 
University, Fuling People’s Hospital of Chongqing, Chongqing Wansheng Economic 
and Technological Development Zone People's Hospital, the First Affiliated Hospital 
of Kunming Medical University and Heping Hospital Affiliated to Changzhi Medical 
College will be the cooperating unit. This study is designed to evaluate the efficacy and 
safety of finerenone in patients with PA. Patients diagnosed with PA are randomly 
assigned to receive oral finerenone or spironolactone for 12 weeks, respectively. Blood 
pressure, renin, blood potassium and other indicators of the patients are observed, and 
the efficacy and safety of the two groups were compared. 
Patients will be instructed to bring their study drug to all clinical site visits. Patients 
should not exercise, smoke, or consume caffeinated beverages or food for at least 2 
hours prior to each clinical site visit. All clinical site visits will take place between 7:00 
a.m. and 12:00 a.m. 
 
3.2 Study Visit 
This study will consist of 2 periods: 
1. A Screening Period (Screening Visit [Visit 1]) of up to 2 weeks; 
2. A Treatment Period (Visits 2 to 7) of 12 weeks; 
Patients will complete at least 7 total visits over a period of approximately 3 months, 
including 5 Clinic Visits and 2 Telephone Visits. Additional Unscheduled Visits may 
occur at any time during the study. 
 
Screening Period (Visit 1, Week -2~0) 
Patients will provide informed consent at the Screening Visit (Visit 1) and undergo 
assessment for Inclusion/Exclusion Criteria. All patients will undergo 24-hour ABPM 

6 
 
at the first visit. 
 
Patients with a confirmed diagnosis of PA who are willing to participate in the study 
are into the Screening Period. PA is defined as having a positive result of screening and 
confirmatory tests. Screening positive is defined as plasma aldosterone-to-renin ratio 
(ARR) ≥ 20(pg/ml)/(μIU/ml) or ARR≥300 pg/ml)/(ng/ml/hr) [ARRs defined as having 
a positive(pg/ml)/(ng/ml/hr) can be considered positive if the patients with hypokalemia 
(serum potassium < 3.5mmol/L) or adrenal nodules (diameter > 1cm)]. Plasma 
aldosterone concentration (PAC) post captopril challenge test (CCT) ≥ 110 pg/ml or 
PAC post seated saline infusion test (SSIT) ≥ 80 pg/ml is considered positive. 
 
 
For the screening test and the confirmatory tests, antihypertensive medication is 
withheld or changed according to the guideline. Treatment with diuretics is withheld 
for at least 4 weeks. β-blockers, angiotensin-converting enzyme inhibitors, and 
angiotensin-II receptor blockers are stopped for at least 2 weeks. Only the non-
dihydropyridine calcium channel blocker, terazosin, and doxazosin are allowed for 
uncontrolled hypertension.  
 
Treatment Period (Visits 2 to 7, Week 0~12) 
All patients who remain on a stable regimen of antihypertensive treatment, or who are 
not taking any antihypertensive medications through the Screening Period will be 
eligible for randomization. Eligible patients will be contacted via Clinic Visits (Visit 2) 
to be informed about the study qualification and to schedule their treatment period. 
Eligible patients will be randomized 1:1 into one of the two treatment groups 
(finerenone and spironolactone).  
 
Patients will complete at least 5 total visits over the treatment period of 12 weeks, 
including three Clinic Visits and two Telephone Visits. Clinical Visits (Visit 4, 6 and 7) 
are conducted on Week 4, Week 8 and Week 12 (the last day of the treatment period), 
and two Telephone Visits (Visit 3 and Visit 5) are conducted on Week 2 and Week 10. 
Additional Unscheduled Visits may occur at any time during the study period. 
 
If the office blood pressure remains uncontrolled on Week 4 (ie, systolic blood pressure 
≥140mmHg or diastolic blood pressure ≥90mmHg], finerenone and spironolactone 
will be increased to 40mg per day (the maximum dose). Patients will also be monitored 
for events of special interest associated with the study medication, including 

7 
 
hyperkalemia, hypotension, impotence, gynecomastia and menstrual abnormalities, in 
these instances, the dose is either maintained or decreased, as determined by the 
investigator. When the patient's blood pressure is up to target, if the patient's 
hypokalemia is not controlled (i.e., the potassium is <3.5mmol on the date of follow-
up), thedose will also be increased to 40mg per day. 
 
Study drug (finerenone or spironolactone) dispensing may occur at any time starting at 
Visit 2 and before Visit 7. On Clinical Visit days, patients will self-administer the 
morning dose of background antihypertensive medications at home and withhold the 
study drug. At the clinical site, patients will self-administer the morning dose of study 
drug under the supervision of site staff after completion of pre-dose evaluations and 
laboratory sampling. Between clinical site visits, patients will continue taking their 
study drug once daily by mouth at approximately the same time each morning. The 
primary efficacy endpoint evaluation will take place at the End of Treatment (Visit 7). 
 
Study visits will follow the Schedule of Procedures (Appendix A). 
 
4. Dosage and Route of Administration: 
Finerenone tablets and spironolactone tablets will be administered during the Treatment 
Period. Finerenone and spironolactone doses to be tested in this study are 20mg or 40 
mg.  
Patients will receive finerenone tablets of either their assigned dose or matching 
spironolactone tablets during the Treatment Period, starting at Visit 2 and concluding at 
Visit 7. 
 
 
5. Statistical Analyses: 
The following analysis populations are defined for the different types of data analysis: 
 
Intention-to-treat (ITT) Population 
The ITT Population will include all patients randomized into the study. Treatment 
classification will be based on the randomized treatment; 
 
Modified intention-to-treat (mITT) Population 
The mITT Population will include patients randomized and received at least 1 dose of 
the study drug. Treatment classification will be based on the randomized treatment. The 
mITT population will be used for the primary analysis of all efficacy endpoints; 
 
Per Protocol (PP) Population 
The PP Population will include all patients in the mITT population and who did not 

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experience a major protocol deviation that potentially impacted the primary efficacy 
endpoint. The PP population, along with the reason for exclusion, will be finalized prior 
to study end. 
 
Safety Population; 
The Safety Population will include all patients who receive at least 1 dose of any 
randomized study drug. Treatment classification will be based on the actual treatment 
received. The Safety Population will be the primary population used for the safety 
analyses. 
 
Efficacy analysis 
The primary efficacy analysis will compare the change in 24-hour SBP assessed by 
ABPM from baseline (Visit 2) to the End of Treatment (Visit 7) between finerenone 
and spironolactone. Statistical analyses will be primarily descriptive. Descriptive 
statistics (eg, mean, standard deviation, median, minimum and maximum) will be 
presented for continuous variables. Frequencies and percentages will be presented for 
categorical and ordinal variables. 
 
Safety analysis 
The safety will be assessed from the time of informed consent until the end of the 
Follow-up Period. The Safety Population will be the primary population for the safety 
analysis. All safety endpoints will be summarized descriptively. 
 
 
.

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Table of Contents 
Synopsis..................................................................................................................................... 2 
Title: ...................................................................................................................................... 2 
1.Objectives： ....................................................................................................................... 2 
2. Efficacy Endpoints: ........................................................................................................... 2 
3.Population: .......................................................................................................................... 3 
3.Study Design and Duration ................................................................................................ 5 
4. Dosage and Route of Administration: ............................................................................... 7 
5. Statistical Analyses:........................................................................................................... 7 
Table of Contents ...................................................................................................................... 9 
List of Abbreviations and Definition of Terms ....................................................................... 11 
1. 
Introduction ..................................................................................................................... 13 
1.1 Rationale ........................................................................................................................ 13 
1.2 Risk/Benefit ................................................................................................................... 14 
2. 
Study Objectives .............................................................................................................. 15 
2.1 The Primary Objective .................................................................................................. 15 
2.2 The Secondary Objective .............................................................................................. 15 
3 
Study Description ............................................................................................................ 15 
3.1 Summary of Study Design ............................................................................................. 15 
3.2 Study visit ...................................................................................................................... 16 
4 
Selection and Withdrawal of Patients .............................................................................. 18 
4.1 Inclusion Criteria ........................................................................................................... 18 
4.2 Exclusion Criteria .......................................................................................................... 18 
4.3 Withdrawal Criteria ....................................................................................................... 19 
4.4 Early Termination Procedures ....................................................................................... 20 
4.5 Criteria for Temporary Suspension of Dosing .............................................................. 20 
5 
Study Treatments ............................................................................................................. 21 
5.1 Treatment group ............................................................................................................ 21 
5.2 Randomization and Treatment Period ........................................................................... 21 
5.3 Drug Supplies ................................................................................................................ 21 
5.4 Treatment Adherence .................................................................................................... 21 

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5.5 Prior and Concomitant Medications and/or Procedures ................................................ 22 
5.6 Rescue therapy .............................................................................................................. 22 
5.7 Treatment for Hypokalemia .......................................................................................... 22 
6 
Study Procedures ............................................................................................................. 23 
6.1 Informed Consent .......................................................................................................... 23 
6.2 Screening Period (Visit 1, Week -2 ~0) ........................................................................ 23 
6.3 Treatment Period ........................................................................................................... 23 
7 
Efficacy Assessments ...................................................................................................... 25 
7.1 Primary Efficacy Endpoint ............................................................................................ 25 
7.2 Secondary Efficacy Endpoints ...................................................................................... 26 
7.3 Exploratory Endpoints ................................................................................................... 26 
8 
Safety Assessments ......................................................................................................... 26 
8.1 Safety Endpoints ............................................................................................................ 26 
8.2 Adverse Events .............................................................................................................. 26 
8.3 Serious Adverse Events ................................................................................................. 27 
8.4 Serious Adverse Event Reporting ................................................................................. 28 
8.5 Management of Potassium Levels ................................................................................. 28 
8.6 Pregnancy Reporting ..................................................................................................... 28 
9 
Blood Pressure Measurement .......................................................................................... 28 
10 Statistics ........................................................................................................................... 30 
10.1 Analysis Populations ................................................................................................... 30 
10.2 Efficacy analysis .......................................................................................................... 30 
10.3 Safety Analysis ............................................................................................................ 30 
10.4 Sample Size ................................................................................................................. 31 
11 Data Management and Record Keeping .......................................................................... 31 
12 Data Collection and Handling ......................................................................................... 32 
13 Investigator Requirements and Quality Control .............................................................. 33 
13.1 Ethical Conduct of the Study ....................................................................................... 33 
13.2 Informed Consent ........................................................................................................ 33 
13.3 Publication policy and use of data ............................................................................... 33 
14 References ....................................................................................................................... 35 
Appendix A: schedule of procedures ...................................................................................... 37 

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List of Abbreviations and Definition of Terms 
Abbreviation 
Definition 
PA 
Primary Aldosteronism 
ABPM 
Ambulatory Blood Pressure Monitoring 
AE 
Adverse Event 
SBP 
Systolic Blood Pressure 
TEAE 
Treatment-Emergent Adverse Event 
DBP 
Diastolic Blood Pressure 
ARR 
Aldosterone-to-Renin Ratio 
PAC 
Plasma Aldosterone Concentration 
CCT 
Captopril Challenge Test 
SSIT 
Seated Saline Infusion Test 
MRA 
Mineralocorticoid Receptor Agonist 
BMI 
Body Mass Index 
NYHA 
New York Heart Association 
CABG 
Coronary Artery Bypass Grafting 
PCI 
Percutaneous Coronary Intervention 
PRC 
Plasma Renin Concentration 
SAE 
Serious Adverse Event 
ITT 
Intent-to-Treat 
mITT 
Modified Intention-to-treat 
DMSB 
Data Safety Monitoring Board 
TAE 
Treatment Adverse Event 
PPS 
Per Protocol Set 
SS 
Safety Set 

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PASS 11 
Power Analysis and Sample Size Software 11 
EH 
Essential Hypertension 
CVD 
Cardiovascular Disease 
CKD 
Chronic Kidney Disease 
MR 
Mineralocorticoid Receptor 
ARTS 
Mineralocorticoid Receptor Antagonist Tolerability 
Study 
HFrEF 
Heart Failure with Reduced Ejection Fraction 
eGFR 
Estimated Glomerular Filtration Rate 
T2DM 
Type 2 Diabetes Mellitus 
DKD 
Diabetic Kidney Disease 
ARTS-DN 
Mineralocorticoid Receptor Antagonist Tolerability 
Study-Diabetic Nephropathy 
CRF 
Case Report Form 
 

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1. Introduction  
Primary aldosteronism (PA) is one of the most common causes of secondary 
hypertension. Compared to patients with essential hypertension (EH), patients with PA 
have a higher risk of cardiovascular disease (CVD) and all-cause mortality1-2. Therefore, 
early treatment is important for PA prognosis. The treatment is different based on PA 
subtypes. Unilateral PA is recommended to be treated with surgery, while bilateral PA 
is mainly treated with an oral mineralocorticoid receptor antagonist (MRA)3. 
Spironolactone, a non-selective MRA, has traditionally been used in the management 
of PA3. But its use has been limited by adverse effects such as gynecomastia, 
mastodynia, and menstrual abnormalities due to a high-binding affinity for 
progesterone or androgen receptors, and it increases the risk of hyperkalemia in patients 
with stage 3 or higher chronic kidney disease (CKD) 4-5.  
Finerenone is a novel non-steroidal MRA, with higher selectivity towards the 
mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding 
affinity than eplerenone. This combination of potency and selectivity towards the MR 
along with balanced tissue distribution in the heart and kidney compared with 
spironolactone or eplerenone may lead to more pronounced cardiorenal protection, 
particularly in high-risk patients with impaired kidney function. The FIDELIO-DKD 
study indicated that in patients with type 2 diabetes combined with chronic kidney 
disease, the overall adverse event rate of finerenone treatment was not significantly 
different compared with placebo (87.3% vs 87.5%, respectively)6. Further, the phase 2b 
ARTS-Diabetic Nephropathy trial confirmed the safety of finerenone in patients with 
diabetic kidney disease7. In addition, the phase 2a Mineralocorticoid Receptor 
antagonist Tolerability Study (ARTS) trial showed that finerenone had comparable 
efficacy to spironolactone in patients with HFrEF and mild CKD, with smaller increases 
in serum potassium level and smaller decreases in estimated glomerular filtration rate 
(eGFR)8.  
 
1.1 Rationale 
It is well recognized that renal epithelial MRs modulate salt and volume handling and 
BP regulation by the kidney. MRs may also modulate BP through effects on endothelial 
and vascular function. Reductions in BP load on the vasculature can protect against 
target organ damage in patients with CKD associated with T2D. Therefore, the impact 
of MRAs including finerenone on pathways regulating BP load on the vasculature 
should be considered.  
Previous trials have reported conflicting data about the antihypertensive effects of 

14 
 
finerenone. A study by Filippatos et al demonstrated that finerenone can reduce SBP by 
3.31 mmHg in 1530 DKD patients with a history of CVD and 3.11 mmHg in 1303 
patients without a history of CVD9. Bakris et al included 821 patients with diabetes and 
high or very high albuminuria, suggesting that the mean differences of SBP between 
the placebo and 7.5-, 10-, 15-, and 20-mg/d finerenone groups are -2.8mmHg, 
0.1mmHg, −5.1mmHg and−4.7mmHg7. Agarwal et al included 823 patients with type 
2 diabetes and CKD who were randomized into a placebo or finerenone group, they 
found the 10-, 15-, and 20-mg/d finerenone groups exhibit a change in 24-h SBP of -
8.3mmHg, -11.2mmHg and -9.9mmHg, respectively10. They also evaluated the 
antihypertensive effect of finerenone in resistant hypertension of CKD, the results 
indicate that finerenone is associated with a lower SBP reduction compared with 
spironolactone11.  
We conducted a randomized pilot study to investigate the antihypertensive efficacy and 
safety of finerenone versus spironolactone in patients with PA. In this pilot study, a total 
of 60 patients underwent randomization. The mean change of daytime SBP in the 
finerenone group was -9.9±13.0 mmHg, which was not significantly different from that 
in the spironolactone group (-7.8±10.2 mmHg, P=0.49). Changes in daytime DBP (-
4.9±7.9 mmHg for finerenone and -5.0±8.4 mmHg for spironolactone, P=0.96), 24-
hour SBP (-10.9±12.5 mmHg for finerenone and -7.8±9.5 mmHg for spironolactone, 
P=0.29),24-hour DBP (-5.9±7.4 mmHg for finerenone and --4.7±6.7 mmHg for 
spironolactone, P=0.50), office SBP (-17.7±19.7 mmHg for finerenone and -17.1±19.0 
mmHg for spironolactone, P=0.90), and office DBP (-9.1±8.3 mmHg for finerenone 
and -6.8±11.8 mmHg for spironolactone, P=0.40) were similar in the two groups. This 
study provides information for large-scale clinical studies. Therefore, we are planning 
a multicenter randomized clinical trial next.  
 
1.2 Risk/Benefit 
1.2.1 Potential Risks 
Due to MRA’s mode of action, hyperkalemia is an important identified risk which is 
also identified from previous studies. Patients with pre-existing renal impairment are at 
an increased risk of experiencing clinically significant hyperkalemia. However, 
considering that many patients with PA also have concurrent hypokalemia, the risk will 
be reduced. Moreover, Spironolactone is a non-selective MRA that can bind to and 
inhibit the androgen receptor, leading to potential anti-androgenic adverse effects with 
long-term use. These adverse effects may include gynecomastia, impotence, menstrual 
disorders, breast-distending pain, and the risk of hyperkalemia.  
In our previous pilot study, we also evaluated the safety of hyperkalemia and renal 

15 
 
function injury. Adverse events were reported in six patients receiving spironolactone 
(20.7%), including one patient who reported hyperkalemia, compared to none in the 
finerenone group. No patients in either group discontinued treatment due to adverse 
events. 
Like any antihypertensive therapy, there is a theoretical risk of hypotension from 
finerenone or spironolactone. If administered, any standard-of-care antihypertensives 
that may be given during the study as add-on treatments for high blood pressure also 
contribute to this risk. The onset of action of finerenone and spironolactone is predicted 
to be gradual and blood pressure will be monitored closely.  
 
1.2.2 Potential Benefits 
Finerenone or spironolactone will be administered to patients with PA. Following the 
administration of a therapeutically effective dose of Finerenone and spironolactone, 
patients may experience a reduction in blood pressure. This may potentially reduce the 
risk of target organ damage and cardiovascular events associated with hypertension and 
high aldosterone levels.  
 
2. Study Objectives  
2.1 The Primary Objective 
To evaluate the antihypertensive efficacy of finerenone compared to spironolactone in 
patients with PA after 12 weeks of treatment. 
2.2 The Secondary Objective 
The secondary objective will include the followings:  
1) To evaluate efficacy on hypokalemia of finerenone compared to spironolactone in 
patients with PA after 12 weeks of treatment. 
2) To evaluate efficacy on renin of finerenone compared to spironolactone in patients 
with PA after 12 weeks of treatment. 
3) To evaluate safety of finerenone compared to spironolactone in patients with PA 
after 12 weeks of treatment. 
 
3 Study Description 
3.1 Summary of Study Design 
The study is a multicenter, randomized controlled trial. The First Affiliated Hospital of 
Chongqing Medical University will be the responsible unit, and the Affiliated Hospital 
of Southwest Medical University, the Third Xiangya Hospital of Central South 

16 
 
University, Fuling People’s Hospital of Chongqing, Chongqing Wansheng Economic 
and Technological Development Zone People's Hospital, the First Affiliated Hospital 
of Kunming Medical University and Heping Hospital Affiliated to Changzhi Medical 
College will be the cooperating unit. Patients diagnosed with PA are randomly assigned 
to receive oral finerenone or spironolactone for 12 weeks, respectively. Blood pressure, 
renin, blood potassium and other indicators of the patients are observed, and the 
efficacy and safety of the two groups were compared. 
Patients will be instructed to bring their study drug to all clinical site visits. Patients 
should not exercise, smoke, or consume caffeinated beverages or food for at least 2 
hours prior to each clinical site visit. All clinical site visits will take place between 7:00 
a.m. and 12:00 a.m. 
 
3.2 Study visit 
This study will consist of 2 periods: 
1. A Screening Period (Screening Visit [Visit 1]) of up to 2 weeks; 
2. A Treatment Period (Visits 2 to 7) of 12weeks; 
Patients will complete at least 7 total visits over a period of approximately 3 months, 
including 5 Clinic Visits and 2 Telephone Visits. Additional Unscheduled Visits may 
occur at any time during the study. 
 
Screening Period (Visit 1, Week -2~0) 
Patients will provide informed consent at the Screening Visit (Visit 1) and undergo 
assessment for Inclusion/Exclusion Criteria. All patients will undergo 24-hour ABPM 
at the first visit. 
 
Patients with a confirmed diagnosis of PA who are willing to participate in the study 
are into the Screening Period. PA is defined as having a positive result of screening and 
confirmatory tests2,11-14. Screening positive is defined as plasma aldosterone-to-renin 
ratio (ARR) ≥ 20(pg/ml)/(μIU/ml) or ARR≥300 pg/ml)/(ng/ml/hr). Plasma aldosterone 
concentration (PAC) post captopril challenge test (CCT) ≥ 110 pg/ml or PAC post 
seated saline infusion test (SSIT) ≥ 80 pg/ml is considered positive.  
[Note: ARR≥10(pg/ml)/(μIU/ml) or ARR≥150(pg/ml)/(ng/ml/hr) can be considered 
positive if the patients with hypokalemia (serum potassium < 3.5mmol/L) or adrenal 
nodules (diameter > 1cm)]. 
 
For the screening test and the confirmatory tests, antihypertensive medication is 
withheld or changed according to the guideline. Treatment with diuretics is withheld 

17 
 
for at least 4 weeks2,13. β-blockers, angiotensin-converting enzyme inhibitors, and 
angiotensin-II receptor blockers are stopped for at least 2 weeks. Only the non-
dihydropyridine calcium channel blocker, terazosin, and doxazosin are allowed for 
uncontrolled hypertension.  
 
Treatment Period (Visits 2 to 7, Week 0~12) 
All patients who remain on a stable regimen of antihypertensive treatment, or who are 
not taking any antihypertensive medications through the Screening Period will be 
eligible for randomization. Eligible patients will be contacted via Clinic Visits (Visit 2) 
to be informed about the study qualification and to schedule their treatment period. 
Eligible patients will be randomized 1:1 into 1 of the 2 treatment groups (Finerenone 
and spironolactone).  
 
Patients will complete at least 5 total visits over a period of approximately 12 weeks, 
including three Clinic Visits and two Telephone Visits. Clinical Visits (Visit 4 and Visit 
5) are conducted on Week 4, Week 8 and Week 12 (the last day of the treatment period), 
and two Telephone Visits (Visit 3 and Visit 5) are conducted on Week 2 and Week 10. 
Additional Unscheduled Visits may occur at any time during the study period. 
 
If the office blood pressure remains uncontrolled on Week 4 (ie, systolic blood pressure 
[SBP] ≥140 mmHg or diastolic blood pressure [DBP] ≥90 mmHg), the dose of 
finerenone and spironolactone will be increased to 40mg per day (the maximum dose). 
Patients will also be monitored for events of special interest associated with the study 
medication, including hyperkalemia, hypotension, impotence, gynecomastia and 
menstrual abnormalities, in these instances, the dose is either maintained or decreased, 
as determined by the investigator. When the patient's blood pressure is up to standard, 
if the patient's hypokalemia is not controlled (i.e., the potassium is <3.5mmol on the 
date of follow-up), the patient will also be increased to 40mg per day. 
 
Study drug (finerenone or spironolactone) dispensing may occur at any time starting at 
Visit 2 and before Visit 7. On Clinical Visit days, patients will self-administer the 
morning dose of background antihypertensive medications at home and withhold the 
study drug. At the clinical site, patients will self-administer the morning dose of study 
drug under the supervision of site staff after completion of pre-dose evaluations and 
laboratory sampling. Between clinical site visits, patients will continue taking their 
study drug once daily by mouth at approximately the same time each morning. The 
primary efficacy endpoint evaluation will take place at the End of Treatment (Visit 7). 

18 
 
 
Study visits will follow the Schedule of Procedures (Appendix A). 
4 Selection and Withdrawal of Patients 
4.1 Inclusion Criteria 
Patients who meet all of the following criteria will be eligible to participate: 
1) Aged between 18-75, male or female; 
2) With confirmed PA diagnosis (screening positive and at least one confirmatory test 
is positive); 
NOTE: Screening positive is defined as plasma aldosterone-to-renin ratio (ARR)≥ 
20(pg/ml)/(μIU/ml) or ARR≥300(pg/ml)/(ng/ml/hr). Plasma aldosterone concentration 
(PAC) post captopril challenge test (CCT) ≥ 110 pg/ml or PAC post seated saline 
infusion test (SSIT) ≥ 80 pg/ml is considered positive. [ARR≥10(pg/ml)/(μIU/ml) or 
ARR≥150(pg/ml)/(ng/ml/hr) can be considered positive if the patients with hypokalemia 
(serum potassium < 3.5mmol/L) or adrenal nodules (diameter > 1cm)]. 
3) Not taking any antihypertensive drugs or on a stable regimen of antihypertensive 
agents other than MRA for more than four weeks before screening; 
4) With a mean seated office SBP ≥ 140 or DBP ≥ 90 mmHg; 
5) Able and willing to give informed consent for participation in the clinical study. 
 
4.2 Exclusion Criteria 
1) Planning to have subtyping examinations of PA (eg. adrenal vein sampling, PET-
CT) within 3 months; 
2) 
Planning to have adrenal surgery or other surgery within 3 months 
3) 
With a mean seated office SBP ≥ 180mmHg or DBP ≥ 110mmHg before 
randomization; 
Note: Mean seated BP is defined as the average of 3 seated BP measurements at any 
single clinical site visit. If the patient did not take their regularly scheduled 
antihypertensive medications prior to the visit, 1 BP re-test is allowed within 2 days 
after taking the medications. 
4) Night shift worker; 
5) Has a body mass index (BMI) ≥ 30 kg/m2 at screening; 
6) Has uncontrolled diabetes with fasting blood glucose (FBG) ≥13.3mmol/L at 
screening; 
7) Has uncontrolled chronic diseases; 
8) Has other known secondary hypertension (eg, renal artery stenosis, Cushing's 
syndrome, pheochromocytoma, or aortic coarctation); 

19 
 
9) Has known and documented heart failure (New York Heart Association [NYHA] 
class III or IV), liver transaminase levels are more than twice the upper limit of 
normal; 
10) Has had CABG other major cardiac surgery (eg, valve replacement), peripheral 
arterial bypass surgery, or PCI within 6 months before screening; 
11) Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute 
coronary syndrome, or hospitalization for heart failure within 6 months before 
screening; 
12) Has poor compliance that can not fully participate in the study; 
13) Has hyperkalemia with serum potassium > 5.0mmol/L without potassium 
supplementation; 
14) Has a history of uncontrolled malignant tumor;  
15) The office blood pressure measurements difference of more than 20mmHg in both 
arms 
16) Unwilling or unable to stop taking sex hormones, glucocorticoids, non-steroidal 
anti-inflammatory drugs, cyclosporine, tacrolimus, or antidepressants; 
17) Is pregnant, breastfeeding, or planning to become pregnant during the study; 
18) Complicated with severe mental illness; 
19) Has had prior organ transplant; 
20) Has a history of allergy to Finerenone or spironolactone; 
21) Has typical consumption of ≥ 15 alcoholic drinks weekly; 
Note: 1 drink of alcohol is equivalent to 360ml beer, 45ml spirits, or 150ml wine 
22) Has participated in another clinical study involving any investigational drug within 
30 days prior to screening； 
23) Female of childbearing potential refusing to use non-hormonal methods of 
contraception during the study period; 
24) Refuse to get rid of grapefruit or grapefruit juice while receiving finerenone 
treatment; 
25) Other situations that the investigator assesses the subject as unable to complete the 
trial. 
 
4.3 Withdrawal Criteria 
Participation of patients in this clinical study will be discontinued for any of the 
following reasons: 
1) The patient withdraws consent or requests discontinuation from the study for any 
reason; 
2) Hypertensive emergencies15, i.e., systolic blood pressure ≥180 or diastolic blood 

20 
 
pressure ≥110mmHg, accompanied by target organ damage, should be withdrawn from 
the study and treated according to medical routine; Patients with the above mentioned 
poor blood pressure control during treatment, but no discomfort, can wait for blood 
pressure retest on the second day, if the systolic blood pressure is still ≥180 or diastolic 
blood pressure ≥110mmHg, then withdraw from the study; 
3) The patient used prohibited concomitant medications (refer to 5.5) for more than 1 
week, and is still using them 2 weeks before the last visit of the study; 
4) The patient has any SAE, clinically significant AE, severe laboratory abnormality,  
intercurrent illness, or other medical condition which indicates to the Investigator that 
continued participation is not in the best interest of the patient; 
5) The patient fails to comply with protocol requirements or study-related procedures; 
6) The patient becomes pregnant. 
 
If a patient withdraws prematurely from the study due to the above criteria or any other 
reason, they will be requested to undergo the Early Termination Procedures and site 
staff should make every effort to complete the full panel of assessments scheduled for 
the End of Treatment (Visit 7). The reason for patient withdrawal must be documented 
in the case report form (CRF). Patients should still attend study visits after Early 
Termination for safety monitoring. 
 
In the case of patients lost to follow-up, attempts to contact the patient must be made 
and documented in the patient’s medical records. Withdrawn patients will not be 
replaced. 
 
4.4 Early Termination Procedures 
The End of Treatment for patients completing the study is Visit 7. For patients who are 
withdrawn from the study prior to completion, all Visit 6 procedures will be performed 
at the Early Termination Visit. 
 
4.5 Criteria for Temporary Suspension of Dosing 
Dosing of patients in this clinical study will be suspended temporarily for any of the 
following reasons: 
• Any SAE that is deemed related to the study drug; 
• Withdrawal of a patient from the study for safety-related reasons; 
•Mild to moderate AEs that is deemed related to the study drug and the patients could 
not tolerate continued treatment 
• Potassium ≥5.5 mEq/L; the patient should stop study drug dosing and present to the 

21 
 
clinical site immediately for repeat testing. 
 
5 Study Treatments 
5.1 Treatment group 
Eligible patients will be randomized in a 1:1 ratio to one of the following groups: 
 
20mg finerenone; or 
 
20mg spironolactone. 
We will double the dose of finerenone or spironolactone (up to a maximum dose of 40 
mg/d) every 4 weeks if mean office seated BP remains ≥140/90 mmHg or the 
hypokalemia is uncontrolled.  
 
5.2 Randomization and Treatment Period 
Patients who meet all eligible criteria will be randomized 1:1 into 1 of the 2 treatment 
groups (finerenone and spironolactone). The dose used in the assigned regimen will be 
doubled after 4 weeks if, at that time, the patient remains a mean office seated BP of 
140 mm Hg or higher (systolic) or 90 mm Hg or higher (diastolic): at week 4, the dose 
will be doubled from 20 mg once daily to 40 mg once daily (maximum dose) in both 
finerenone and spironolactone group. The dose will not be increased if the patient has 
severe TAEs. In these instances, the dose is either maintained or decreased, as 
determined by the investigator. 
 
5.3 Drug Supplies 
After eligible patients randomized into treatment groups, an investigator will dispense 
the corresponding medication based on the group assignment of the patients. 
 
5.4 Treatment Adherence 
At Visits 2 to 7, treatment adherence will be calculated by site staff using pill counts. 
During the Treatment Period, site staff will collect information from the patient 
regarding any delays in taking the study drug and missed study drug doses and record 
them in source files and CRF. 
 
For all protocol-specified doses when the patient is not at the clinical site, patients will 
self-administer study drug at home and continue taking their background 
antihypertensive medications. Each patient will be counseled by site staff at every visit 
on the importance of adhering to their background antihypertensive regimen, study drug, 
and bringing their medications to each clinical site visit.   

22 
 
 
5.5 Prior and Concomitant Medications and/or Procedures 
5.5.1 Excluded Medications and/or Procedures 
 
Any antihypertensive medications other than the background treatment in the 
Screening Period;  
 
Nonsteroidal Anti-inflammatory Drugs; 
 
Licorice; 
 
Strong CYP3A inhibitors (eg. Clarithromycin); 
 
Strong or moderate CYP3A inducers (eg. Rifampin); 
 
Glucocorticoid 
 
Cyclosporine 
 
Tacrolimus 
 
Antidepressants 
 
Estrogenic contraceptives 
For CYP3A inhibitors or inducers, see the online reference at  
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-int 
eractions-table-substrates-inhibitors-and-inducers. 
 
5.5.2 Documentation of Prior and Concomitant Medication Use 
All concomitant medications and concurrent therapies will be documented. Dose,  
route, unit frequency of administration, indication for administration, and dates of 
medication administration will also be captured in source documents and on the 
appropriate CRF. 
 
5.6 Rescue therapy 
If poor blood pressure control persists (SBP≥160mmHg or DPB≥100 mmHg) after 
adjusting spironolactone or finerenone to the maximum dose for 2 to 4 weeks, 
amlodipine can be treated remedial (5 to 10mg/ day)  
 
5.7 Treatment for Hypokalemia 
For patients with low potassium (serum potassium <3.5mmol), potassium 
supplementation will be given according to the severity of hypokalemia before 
randomization, and potassium supplementation is stopped 2 weeks after starting MRA 
treatment, and then the treatment plan is adjusted according to the blood potassium 
reexamination in V4 (4 weeks after starting MRA treatment): If the serum potassium is 
<3.5mmol/1, MRA should be supplemented with 20mg qd up to the maximum dose, 
and the serum potassium should be re-checked 4 weeks later (V5), and the treatment 

23 
 
regimen should be adjusted according to the above principles. 
 
6 Study Procedures 
6.1 Informed Consent 
Written consent will be obtained from all patients before any protocol-specific 
procedures are performed. 
Information about the study will be given to the patient both verbally and in writing. 
The written patient information will explain the objectives of the study, potential risks 
and benefits, and the impact of early withdrawal on the scientific validity of the study. 
The patient must have adequate time to read the information and to ask the Investigator 
any questions. The Investigator must ensure that the patient has understood the 
information provided before written consent is obtained. If there is any doubt as to 
whether the patient has understood the written or verbal information, the patient must 
not enter the study.  
 
6.2 Screening Period (Visit 1, Week -2 ~0) 
For the screening test and the confirmatory tests, antihypertensive medication is 
withheld or changed according to the guideline.  
 
The following procedures will be performed at Visit 1: 
• Obtain informed consent; 
• Assess eligibility based on Inclusion/Exclusion Criteria; 
• Perform 24-hour ABPM; 
• Record demographics and medical/surgical history; 
• Assess and record AEs; 
• Record prior medications; 
• Measure weight and height; 
• Record vital signs; 
• Measure seated BP and heart rate; 
• ECG; 
•Collect urine sample for urinalysis and blood samples for FPG, ALT, AST, creatinine, 
electrolyte, PAC and PRC,UACR 
 
6.3 Treatment Period 
6.3.1 Baseline and Randomization (Visit 2, Day 0) 
The following procedures will be performed at Visit 2: 

24 
 
• Check inclusion and exclusion criteria; 
• Randomization to finerenone or spironolactone once daily; 
• Record pre-dose office seated BP; 
• Dispense the study drug; 
• Record concomitant medications; 
• Record adverse events;  
• First administration of study drug; 
• Perform the following routine safety evaluations pre-dose; 
• Record weight; 
• Record vital signs; 
• Perform physical examination (general appearance, skin, heart, lungs, and abdomen); 
 
6.3.2 Telephone Call (Visit 3 and Visit 5, Week 2 and Week 10 respectively) 
  The following procedures will be performed at Visit 3 and Visit 5: 
• Assess and record AEs; 
• Record concomitant medications; 
• Perform adherence counselling; 
• Record home seated BP; 
•Provide the following instructions for the next visit. 
  Patients should take their scheduled morning doses of background antihypertensive 
medications at home on the morning of their next visit; Patients must bring their 
background antihypertensive medications to the clinical site for their next visit; and 
Patients should not exercise, smoke, or consume caffeinated beverages or food for at 
least 2 hours prior to the next visit. 
 
6.3.3 Visit 4, Week 4.  
The dose used in the assigned regimen will be doubled after 4 weeks if, at that time, the 
patient remains a mean office seated BP of 140 mm Hg or higher (systolic) or 90 mm 
Hg or higher (diastolic): at week 4, the dose will be doubled from 20 mg once daily to 
40 mg once daily (maximum dose) in both finerenone and spironolactone group. 
The following procedures will be performed at Visit 4: 
• Assess and record AEs; 
• Record concomitant medications; 
• Record office seated BP; 
• Assess treatment adherence based on pill counts; 
• Perform the following routine safety evaluations pre-dose; 
• Record weight; 

25 
 
• Record vital signs; 
• Perform physical examination (general appearance, skin, heart, lungs, and abdomen); 
• Measure standing BP and heart rate 
• Collect blood samples for the following: 
    Serum potassium 
Serum creatinine 
6.3.4 Visit 5, Week 8.  
Same to the Visit 4 
 
6.3.5 End of Treatment (Visit 7, Week 12)  
The following procedures will be performed at Visit 6: 
• Perform 24-hour ABPM 
• Assess and record AEs; 
• Record concomitant medications; 
• Assess treatment adherence based on pill counts; 
• Perform the following routine safety evaluations pre-dose; 
• Record weight; 
• Record vital signs; 
• Perform physical examination (general appearance, skin, heart, lungs, and abdomen); 
Measure standing BP and heart rate 
• Collect urine sample for urinalysis; and 
• Collect blood samples for the following: 
     PAC 
     PRC 
     Serum potassium 
     Serum creatinine 
     UACR 
 
Study visits will follow the Schedule of Procedures (Appendix A). 
 
7 Efficacy Assessments 
7.1 Primary Efficacy Endpoint 
The change from baseline in 24-hour systolic blood pressure (SBP) assessed by 24-hour 
ABPM compared to spironolactone after 12 weeks of finerenone therapy in patients 
with PA. 

26 
 
7.2 Secondary Efficacy Endpoints 
 
Change from baseline in 24-hour diastolic blood pressure (DBP) assessed by 24-
hour ABPM; 
 
Blood pressure control rate at the end of the study; 
Note: Blood pressure control rate is defined as the percentage of patients with mean 
seated office BP<140/90 mmHg. 
 
Change from baseline in daytime SBP assessed by 24-hour ABPM; 
 
Change from baseline in daytime DBP assessed by 24-hour ABPM; 
 
Change from baseline in nighttime SBP assessed by 24-hour ABPM; 
 
Change from baseline in nighttime DBP assessed by 24-hour ABPM; 
 
Change from baseline in office SBP;  
 
Change from baseline in office DBP; 
 
Change from baseline in serum potassium; 
 
Hypokalemia control rate at the end of the study 
Note: Hypokalemia control rate is defined as the percentage of hypokalemic patients 
with serum potassium>3.5mmol/l at the end of the study. 
 
Change from baseline in plasma renin. 
 
7.3 Exploratory Endpoints  
The exploratory endpoints will include the followings: 
 
Change from baseline in urinary albumin-to-creatinine ratio (UACR);  
 
Change in the UACR in patients with baseline UACR more than 30 (mg/g Cr). 
 
 
8 Safety Assessments 
8.1 Safety Endpoints 
All safety endpoints will be summarized descriptively. 
The safety endpoints will include the following: 
 
Proportion of subjects with AEs; 
 
SAEs and AEs leading to discontinuation of treatment with study drug; 
 
Change in eGFR from baseline. 
 
8.2 Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation that 
occurs to a patient administered a pharmaceutical product, which does not necessarily 
have a causal relationship with this treatment.  
 

27 
 
8.2.1 Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE as mild, moderate, or 
severe, and will also categorize each AE according to its potential relationship to study 
drug using the categories of YES or NO. 
Mild –    Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
no intervention indicated. 
Moderate – Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (eg, preparing meals, shopping for 
groceries or clothes, using the telephone, managing money). 
Severe –   Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care activities of daily living (ie, bathing, dressing and undressing, feeding self, using 
the toilet, taking medications, and not bedridden); OR life-threatening consequences; 
urgent intervention indicated; OR death related to an AE. 
 
8.2.2 Causality assessment 
The relationship between an AE and the administration of the study drug is to be 
assessed according to the following definitions: 
NO (not related, unlikely to be related) – The time course between the administration 
of study drug and the occurrence or worsening of the AE rules out a causal relationship 
and another cause (concomitant drugs, therapies, complications, etc) is suspected. 
YES (possibly, probably, or definitely related) – The time course between the 
administration of study drug and the occurrence or worsening of the AE is consistent 
with a causal relationship and no other cause (concomitant drugs, therapies, 
complications, etc) can be identified. 
 
8.2.3 Adverse Events of Special Interest 
For this study, AESIs include the following: 
 
Symptoms of decreased kidney function such as oliguria, swelling, and  
foamy urine; 
 
Gynecomastia, impotence, menstrual disorders, and breast-distending pain  
 
Side effects such as itching and dizziness;  
 
8.3 Serious Adverse Events 
An AE is considered serious if, in the view of either the Investigator, it results in any of 
the following outcomes: 
 
Death; 

28 
 
 
A life-threatening AE; 
 
Requires hospitalization or prolongation of existing hospitalizations; 
 
A persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions. 
 
8.4 Serious Adverse Event Reporting  
   All SAEs occurring from the time of informed consent until the end of the study 
must be reported to investigators within 24 hours of the knowledge of the occurrence. 
The Investigator must continue following the patient until the SAE has subsided or until  
the condition becomes chronic in nature, stabilizes (in the case of persistent 
impairment), or the patient dies. 
 
8.5 Management of Potassium Levels 
Potassium will be monitored closely throughout this study, with assessments of 
potassium concentration scheduled at all visits. 
 
For potassium≥5.5 mmol/L, the patient should present to the clinical site immediately 
for repeat testing, and the study drug dosing need not be stopped. According to the retest 
results one week later, the investigator will decide whether to continue the medication.. 
If the potassium is normal, the original dose is given in half, and the retest is conducted 
one week later. 
 
8.6 Pregnancy Reporting 
If a patient becomes pregnant during the study or within the safety Follow-up Period 
defined in the protocol, the Investigator is to stop dosing with study drug(s) 
immediately and the patient should be withdrawn from the study. Early termination 
procedures should be implemented at that time.  
 
9 Blood Pressure Measurement  
BP will be measured at clinic visits using the following standardized procedures 
according to American Heart Association statement15: 
 
Seated office BP should be measured with the same validated arm electronic 
sphygmomanometer by trained clinicians or nurses at any clinical single site visit; 
 
Patients should not exercise, smoke, or consume caffeinated beverages or food 30 
minutes prior to assessment of vital signs and BP measurement; 
 
Patients should be ensured that they have emptied their bladders; 

29 
 
 
Patients should be seated for at least 5 minutes in the examination room with the 
back supported, feet flat on the floor, and the measurement arm supported so that the 
midpoint of the manometer cuff is at heart level; 
 
An appropriately sized cuff should be used with the bladder centered over the 
brachial artery; 
 
The arm with the higher mean BP value at Screening should be used for Screening 
and subsequent BP measurements; 
 
All BP measurements should be obtained at approximately the same time of day 
(7:00am- 10:00am) 
 
Three seated BP measurements (each measurement 1 to 2 minutes apart) should be 
obtained  
 
Using the same arm and the Omron HBP-1320 for monitoring blood pressure at 
each clinical site visit. Mean seated BP is defined as the average of 3 seated BP 
measurements at any single clinical site visit; 
 
If the lowest and highest SBP measurements are >15 mmHg apart, additional 
readings should be performed; and average the last 3 consecutive measurements 
(measurements 2-4). If the measurements are still >15 mmHg apart, take one additional 
reading and average the last 3 consecutive measurements (measurements 3-5). If the 
measurements are still >15 mmHg apart, take one final measurement and average the 
last 3 consecutive measurements (measurements 4-6). 
 
Place cuff of 24-h ambulatory blood pressure on bare arm with tubing passing 
upwards around patient’s neck to be connected to the monitor on the waist to avoid the 
impact of frequent activities.  
 
The 24-h ambulatory blood pressure is assessed every 15 min during waking hours 
and every 30 min during sleep. ABPM data will be summarized separately as 24-hour 
mean, daytime mean and nighttime mean. BP readings at or after 6:00 am and before 
10:00 pm are daytime readings. Readings at or after 10:00 pm and before 6:00 am the 
next day are nighttime readings. ABPM data require a minimum of 20 valid awake and 
seven valid asleep BP readings, and 70% of the reading should be valid reading, if it is 
not up to this standard, the ABPM needs to be re-measured. Patients should be 
instructed to deal with what they are expected to do during a 24-h ABP recording. 
Patients should keep a diary card, reporting major events occurring during the recording 
time, and writing down the name, dose, and time of administration of each prescribed 
drug, the sleeping and awakening times, time of main meals, and also a short description 
of any unusual activity and of any symptoms that might occur. Patient should be also 
instructed to follow their usual daily activities, but to remain still and to keep the arm 

30 
 
hanging down along the body each time the cuff starts inflation during the 
measurements. 
 
Quality control: Special attention must be placed on assessment and maintenance 
of the instrument's accuracy as per the manual that accompanies the instrument. 
 
10 Statistics 
10.1 Analysis Populations 
The following analysis populations are defined for the different types of data analysis: 
 
Intention-to-treat (ITT) Population 
The ITT Population will include all patients randomized into the study. Treatment 
classification will be based on the randomized treatment; 
 
Modified intention-to-treat (mITT) Population 
The mITT Population will include patients randomized and received at least 1 dose of 
any study drug. Treatment classification will be based on the randomized treatment. 
The mITT population will be used for the primary analysis of all efficacy endpoints; 
 
Per Protocol (PP) Population 
The PP Population will include all patients in the mITT population and who did not 
experience a major protocol deviation that potentially impacted the primary efficacy 
endpoint. The PP population, along with the reason for exclusion, will be finalized prior 
to study end. 
 
Safety Population 
The Safety Population will include all patients who receive at least 1 dose of any 
randomized study drug. Treatment classification will be based on the actual treatment 
received. The Safety Population will be the primary population used for the safety 
analyses. 
 
10.2 Efficacy analysis 
The primary efficacy analysis will compare the change in 24-hour SBP assessed by 
ABPM from baseline (Visit 2) to the End of Treatment (Visit 7) between finerenone 
and spironolactone. Statistical analyses will be primarily descriptive. No formal 
hypothesis testing will be conducted. Descriptive statistics (eg, mean, standard 
deviation, median, minimum and maximum) will be presented for continuous variables. 
Frequencies and percentages will be presented for categorical and ordinal variables. 
 
10.3 Safety Analysis 
The safety will be assessed from the time of informed consent until the end of the 

31 
 
Follow-up Period. The Safety Population will be the primary population for the safety 
analysis. All safety endpoints will be summarized descriptively. 
 
10.4 Sample Size 
The assumption of this study is that the antihypertensive effect of finerenone is non-
inferior to spironolactone. The sample size was based on data from our pilot study to 
assess the efficacy and safety of finerenone versus spironolactone in PA. According to 
pilot study, the standard deviation of 24-hour SBP were12.5mmHg in the finerenone 
group and 9.5mmHg in the spironolactone group respectively. Previous studies on 
antihypertensive RCT mostly set blood pressure in the range of 2-6 mmHg as the non-
inferior limit17-19, while the European Society of Hypertension pointed out that a 
difference of less than 5mmHg is clinically acceptable20. Therefore, the non-inferior 
limit is set as 4 mmHg. Using 80% power to measure the antihypertensive effect 
between the two groups, a unilateral significance level α=0.025, a total sample size of 
244, an estimated dropout rate of about 20%, and a final sample size of 244/0.8=306, 
with a target of 153 patients per group. 
 
11 Data Management and Record Keeping 
A Data Safety Monitoring Board (DSMB) will meet periodically to monitor the study. 
The primary function of this committee is safety monitoring, and the committee will 
not discontinue the study for a finding of positive efficacy for any of the doses being 
considered. As part of these reviews, the DSMB will receive summaries of study 
conduct measures as well as safety and efficacy data. The DSMB may recommend 
discontinuing enrollment for a dose for safety or lack of efficacy.  
The DSMB Chair is an expert in PA who is well-versed in GCP management. The 
Chair's responsibilities include facilitating discussions, integrating different 
perspectives, and reaching consensus among the responsible centers. The Chair is also 
committed to participating in DSMB activities throughout the trial period. The DSMB 
will hold regular meetings to review the trial's progress and ensure the research's quality. 
Please see the attachment for the full membership list. The main members include: 
 
Chairman: Yan Ren is an Associate Professor at West China School of Public Health, 
Sichuan University, Chengdu, Sichuan, People's Republic of China.. Her research 
focuses on adrenal disorders, particularly primary aldosteronism. She has rich clinical 
experience in the clinical diagnosis and treatment of adrenal diseases. 
 

32 
 
Bin Peng is a Professor with a PhD in Epidemiology and Health Statistics. He serves 
as the Deputy Director of the Department of Statistics at the School of Public Health, 
Chongqing Medical University. His research and teaching focus on epidemiological 
methods and health data analysis, contributing significantly to public health research 
and education. 
 
Weiping Li is an Associate Professor Department of Information Engineering, First 
Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 
China. He has been engaged in the clinical and basic research of endocrine and 
metabolic diseases for a long time, and is good at the clinical diagnosis and treatment 
of diabetes, hypertension, polycystic ovary syndrome, thyroid and adrenal diseases. 
 
 
12 Data Collection and Handling 
12.1 Case Report Form (CRF) 
The CRF is completed by the investigator based on the original examination report, 
medical history collection, and physical examination results. The CRF should be 
completed timely and ensure that the data entered can be traced from the original record. 
When modifying data, you need to enter the reason and time for the modification and 
sign the name. Authorized personnel is required to confirm the authenticity, 
completeness, and timeliness of the CRF data and to sign it. Paper CRF will be made 
by the researchers into electronic data for analysis. Before the database is locked, the 
research team needs to complete the data cleaning and hold a DSMB meeting to 
determine the analysis population. Decisions made during the DSMB meeting should 
be documented. After the DSMB meeting is passed, the research team confirms that the 
research database in the electronic system is locked, and the data cannot be changed 
after the lock. 
12.2 Data Quality Assurance 
To ensure the data reliable, the following items are made: 
 
Guidance materials are provided to research centers;  
 
Provides training and guidance to researchers and research coordinators. This 
training will provide relevant research protocols, case report forms (CRF); 
 
Regular visits to the research centers;  
 
Receive consultation and contact with research center staff through email, phone, 
we-chat, etc., to review and verify the accuracy of reported data. 
In addition, data will be checked periodically against source files located at the study 

33 
 
center. The investigator will keep all raw data (e.g. laboratory test results, medical 
records, etc.) 
12.3 Data accuracy 
Two researchers will independently input the data to generate two sets of databases. 
Subsequently, data analysis software was used for consistency checks to ensure the 
consistency of the two sets of databases. If any inconsistencies are found, the data will 
be corrected by re-examining the original case report form or laboratory report. This 
method can effectively reduce the possible errors in the process of data entry, and ensure 
the accuracy and reliability of data. 
 
13 Investigator Requirements and Quality Control 
13.1 Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard 
for designing, conducting, recording, and reporting studies that involve human patients. 
Compliance with this standard provides public assurance that the rights, safety, and 
well-being of study patients are protected, consistent with the principles that have their 
origin in the Declaration of Helsinki, and that the clinical study data are credible. The 
ethics committee of The First Affiliated Hospital of Chongqing Medical University 
approved the protocol. 
 
13.2 Informed Consent 
The ICFs must be in compliance with local regulatory requirements, and legal 
requirements. The Investigator must ensure that each study patient is fully informed 
about the nature and objectives of the study and possible risks associated with 
participation and must ensure that the patient has been informed of his/her rights to 
privacy. The Investigator will obtain written informed consent from each patient before 
any protocol-specific activity is performed and should document in the source 
documentation that consent is obtained prior to enrollment in the study. The original 
signed copy of the ICF(s) must be maintained by the Investigator. A copy of the signed 
ICF(s) will be given to the patient.   
 
13.3 Publication policy and use of data 
The investigator has made the information regarding the study protocol publicly 
available on the internet at www.clinicaltrials.gov. 
 
All data, results, and all intellectual property rights in the data and results derived from 

34 
 
the study will be the property of the principal investigator(Qifu Li and Shumin Yang) 
who may utilize them in various ways, such as for submission to government regulatory 
authorities or disclosure to other investigators. 
Following completion of the study, the data may be considered for publication in a 
scientific journal or for reporting at a scientific meeting. Each Investigator is obligated 
to keep data pertaining to the study confidential. The Investigator must consult with the 
principal investigator before any study data are submitted for publication. The principal 
investigator reserves the right to deny publication rights until mutual agreement on the 
content, format, and interpretation of data in the manuscript, and journal selected for 
publication are achieved.

35 
 
14 References 
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aldosteronism screening and diagnosis[J]. Clin Biochem, 2015. 377-387. 
[2] Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: 
Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice 
Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916.  
[3] Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: 
Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice 
Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916.  
[4] Ménard J. The 45-year story of the development of an anti-aldosterone more specific 
than spironolactone. Mol Cell Endocrinol. 2004;217(1-2):45-52. 
[5] Vilela LAP, Almeida MQ. Diagnosis and management of primary 
aldosteronism. Arch Endocrinol Metab. 2017;61(3):305-312.  
[6] Bakris GL, Rajiv A, Stefan DA, et al. Effect of Finerenone on Chronic Kidney 
Disease Outcomes in Type 2 Diabetes.N Engl J Med . 2020 Dec 3;383(23):2219-2229. 
[7] Bakris GL, Agarwal R, Chan JC, et al. Effect of Finerenone on Albuminuria in 
Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 
2015;314(9):884-894. 
[8] Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-
steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic 
heart failure and mild or moderate chronic kidney disease: a randomized, double-blind 
trial. Eur Heart J. 2013;34(31):2453-2463. 
[9] Filippatos G, Anker SD, Agarwal R, et al. Finerenone and Cardiovascular Outcomes 
in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circulation. 
2021;143(6):540-552. 
[10] Agarwal R, Ruilope LM, Ruiz-Hurtado G, et al. Effect of finerenone on ambulatory 
blood pressure in chronic kidney disease in type 2 diabetes. J Hypertens. 
2023;41(2):295-302. 
[11] Agarwal R, Pitt B, Palmer BF, et al. A comparative post hoc analysis of finerenone 
and spironolactone in resistant hypertension in moderate-to-advanced chronic kidney 
disease. Clin Kidney J. 2022;16(2):293-302. Published 2022 Oct 30.  
[12] Song Y, Yang S, He W, et al. Confirmatory Tests for the Diagnosis of Primary 
Aldosteronism: A Prospective Diagnostic Accuracy Study.Hypertension. 2018 
Jan;71(1):118-124.  
[13] Moe T, Karen Y, Ashraf HA, et al. Diagnosis of Primary Aldosteronism by Seated 
Saline Suppression Test—Variability Between Immunoassay and HPLC-MS/MS.J Clin 
Endocrinol Metab . 2020 Mar 1;105(3):dgz150.  
[14] Paolo M, Silvia M, Jaap D, et al. Genetics, prevalence, screening and confirmation 
of primary aldosteronism: a position statement and consensus of theWorking Group on 
Endocrine Hypertension of The European Society of Hypertension.J Hypertens . 2020 
Oct;38(10):1919-1928. 
[15] Mancia G, Kreutz R, Brunström M, et al.2023 ESH Guidelines for the management 
of arterial hypertension The Task Force for the management of arterial hypertension of 

36 
 
the European Society of Hypertension: Endorsed by the International Society of 
Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 
1;41(12):1874-2071. 
[16] Muntner P, Shimbo D, Carey RM, et al.Measurement of Blood Pressure in Humans 
A Scientific Statement From the American Heart Association. Hypertension. 2019 
May;73(5):e35-e66. 
[17] Yang T, Jiang Y, Hao Y, et al. Comparison of bisoprolol to a metoprolol CR/ZOK 
tablet for control of heart rate and blood pressure in mild-to-moderate hypertensive 
patients: the CREATIVE study. Hypertens Res. 2017 Jan;40(1):79-86.  
[18] Oh GC, Lee HY, Chung WJ, et al. Comparison of effects between calcium channel 
blocker and diuretics in combination with angiotensin II receptor blocker on 24-h 
central blood pressure and vascular hemodynamic parameters in hypertensive patients: 
study design for a multicenter, double-blinded, active-controlled, phase 4, randomized 
trial. Clin Hypertens. 2017;23:18. 
[19] Takahara M, Shiraiwa T, Shindo M, et al. Efficacy and safety of 10-mg azilsartan 
compared with 8-mg candesartan cilexetil in Japanese patients with hypertension: a 
randomized crossover non-inferiority trial. Hypertens Res. 2014;37(9):852-857.  
[20]O'Brien E, Atkins N, Stergiou G, et al. European Society of Hypertension 
International Protocol revision 2010 for the validation of blood pressure measuring 
devices in adults [published correction appears in Blood Press Monit. 2010 
Jun;15(3):171-2]. 
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2010;15(1):23-38. 
doi:10.1097/MBP.0b013e3283360e98

37 
 
Appendix A: schedule of procedures 
Visit 
Week 
(Period window) 
Screening and Randomization 
Treatment 
Visit 1 
Week -2~0 
 
Visit 2 
Week 0 
(+/-0) 
Visit 3 
Week 2 
(+/-5 days) 
Visit 4 
Week 4 
(+/-5 days) 
Visit 5 
Week 8 
(+/-5 days) 
Visit 6 
Week 10 
(+/-5 days) 
Visit 7 
Week 12 
(+/-5 days) 
In- and exclusion criteria 
√ 
√ 
 
 
 
 
 
Informed consent 
√ 
 
 
 
 
 
 
Randomization 
 
√ 
 
 
 
 
 
Office blood pressure and heart rate 
√ 
√ 
 
√ 
√ 
 
√ 
Home blood pressure  
 
 
√ 
 
 
√ 
 
Ambulatory blood pressure 
√ 
 
 
 
 
 
√ 
Medical history/Prior medication 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
AE assessment and Pregnancy  
√ 
√ 
√ 
√ 
√ 
√ 
√ 
ECG 
√ 
 
 
√ 
√ 
 
√ 
Laboratory examination 
 
 
 
 
 
 
 
   ARR 
√ 
 
 
√ 
√ 
 
√ 
   Blood routine 
√ 
 
 
 
 
 
 
   Urine routine 
√ 
 
 
 
 
 
 
   Liver function 
√ 
 
 
 
 
 
 
   Renal function 
√ 
 
 
√ 
√ 
 
√ 
   Potassium 
√ 
 
 
√ 
√ 
 
√ 
   UACR 
√ 
 
 
 
 
 
√ 
Study drug dispense 
√ 
 
 
√ 
√ 
 
√ 
Compliance assess 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Guidance adherence 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Provide instructions for next visit 
 
√ 
√ 
√ 
√ 
√ 
 

38