A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Effectiveness of CIN-107 for the Management of Blood Pressure in Patients With Primary Aldosteronism
Phase: PHASE2
Conditions: Primary Aldosteronism, Hyperaldosteronism
Sponsor: AstraZeneca

CLINICAL STUDY PROTOCOL 
A Multicenter, Open-Label Study to Evaluate the Safety, 
Tolerability, and Effectiveness of CIN-107 for the Management of 
Blood Pressure in Patients with Primary Aldosteronism PAGE
Investigational Product.: CIN-107 (generic name: baxdrostat)
Protocol D Code: 
 D6970C00001 
Protocol Number:
SPARK-PA CIN-107-122
Date: 31 March 2023
Version No.: 7.0
 
Sponsor: AstraZeneca AB 
Västra Mälarehamnen 
SE-151 85 Södertälje, Sweden 
Telephone: +46-8-553 260 00 
CONFIDENTIALITY STATEMENT 
The information in this document is confidential and is not to be disclosed without the written 
consent of AstraZeneca AB (hereinafter AstraZeneca) except to the extent that disclosure would 
be required by law and for the purpose of evaluating and/or conducting a clinical study for 
AstraZeneca. The contents of this document may only be disclosed to the Institutional Review 
Board and study personnel directly involved with conducting this protocol. Persons to whom the 
information is disclosed must be informed that the information is confidential and proprietary to 
AstraZeneca and that it may not be further disclosed to third parties. 
 

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SIGNATURE PAGE
Study Title
A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, 
and Effectiveness of CIN-107 for the Management of Blood Pressure in 
Patients with Primary Aldosteronism
Study D Code
D6970C00001
Study Name
SPARK-PA CIN-107-122
Original Protocol 
12 August 2020
Version 2.0
09 October 2020
Version 3.0
03 March 2021
Version 4.0
09 July 2021
Version 5.0
02 April 2022 
Version 6.0
15 September 2022 
Version 7.0
31 March 2023
I, the undersigned, have read this protocol and agree that it contains all necessary information 
required to conduct the study. 
Signature 
Date 
Shira Perl, MD
Global Clinical Head (Hypertension) 
AstraZeneca 
 
 

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INVESTIGATOR AGREEMENT
By signing below, I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by AstraZeneca to study personnel under my supervision. I will discuss this material with them to 
ensure they are fully informed about the study product and study procedures. I will let them know 
that this information is confidential and proprietary to AstraZeneca and that it may not be further 
disclosed to third parties. I understand that the study may be terminated, or enrollment suspended 
at any time by AstraZeneca, with or without cause, or by me if it becomes necessary to protect the 
best interests of the study patients. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board, and International Council for Harmonisation Guidelines for 
Good Clinical Practices.
______________________________________________
____________________
Investigator’s Signature
Date
______________________________________________
Investigator’s Printed Name
 

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SYNOPSIS
Protocol Title:  
A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Effectiveness of CIN-107 
for the Management of Blood Pressure in Patients with Primary Aldosteronism
Protocol Number: D6970C00001
Protocol Name: SPARK-PA CIN-107-122
Name of Investigational Product:
CIN-107 (2, 4, and 8 mg) 
Estimated Number of Study Centers:
Multiple clinical sites in the United States
Trial Duration (months): 
Up to 5 months for Part 1 only. 
Up to 19 months Part 1 plus Part 2/extension 
Phase of Development: 
Phase 2 
Rationale:
Primary aldosteronism (PA) is characterized by autonomous secretion of aldosterone from the zona 
glomerulosa of the adrenal cortex. Aldosterone synthetase inhibitors, by inhibiting aldosterone 
synthesis, provide a direct mechanism to address the primary pathogenesis of the disease. Reducing 
aldosterone levels has the potential to reduce blood pressure (BP), either alone or in combination with 
other antihypertensive agents, improve potassium levels, and reduce the risk of end organ damage. 
CIN-107 is a highly potent, selective, and competitive inhibitor of aldosterone synthase. Based on 
findings from nonclinical studies and single-ascending and multiple-ascending dose clinical studies, 
CIN-107 may be a novel treatment for the deleterious effects of inappropriately elevated aldosterone 
levels resulting in elevated BP in patients with PA. CIN-107 has the potential to offer a new 
therapeutic option aimed at decreasing aldosterone concentrations in plasma and tissues, thus reducing 
both the mineralocorticoid receptor-dependent and mineralocorticoid receptor-independent effects of 
aldosterone.
Objectives:
Primary Objectives: 
The primary objectives of Study D6970C00001 are to evaluate: 
 
The safety and tolerability of CIN-107 in patients with PA at doses from 2 to 8 mg per day for 
12 weeks 
 
The reduction in systolic blood pressure (SBP) with CIN-107 in patients with PA after 
12 weeks of treatment 
Secondary Objectives: 
The secondary objectives of Study D6970C00001 are to evaluate: 
 
The reduction in diastolic blood pressure (DBP) as a function of dose in patients with PA after 
12 weeks of treatment 
 
The change in serum potassium and requirement for potassium supplementation as a function 
of CIN-107 dose 
 
The change in serum sodium and requirement for fluid or mineral replacement as a function of 
CIN-107 dose

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Exploratory Objectives: 
Exploratory objectives are to evaluate: 
 
The correlation of serum aldosterone and plasma aldosterone-to-renin ratio (ARR) changes to 
drug dosage of CIN-107 
 
Relationship between BP reduction and changes in aldosterone and renin levels with CIN-107 
dosages 
The changes in concentration in pharmacodynamic (PD) markers, including but not limited to:
o plasma aldosterone and its relevant precursors (18-OH corticosterone, corticosterone, 
and 11-deoxycorticosterone) 
o plasma cortisol (free and total) and its relevant precursor  
o NT-pro (B-type natriuretic peptide) (NT-proBNP) 
o plasma renin concentration and activity 
o 24-hour urine analytes sodium, potassium, creatinine, albumin, protein, and 
aldosterone 
Pharmacokinetic and Pharmacodynamic Objectives 
The PK-PD objectives are to evaluate:
 
The exposure-response relationships of CIN-107 in patients with PA using measures of safety, 
effectiveness, and/or PD 
 
The relationship between plasma renin, aldosterone, and ARR to the SBP response to CIN-
107 
Extension Part (Part 2) Additional Objectives  
To assess: 
 
The safety and tolerability of CIN-107 in patients with PA at doses from 2 to 8 mg per day for 
patients who elect to participate in the extension study for up to 74 weeks
 The management of blood pressure control for patients who elect to participate in the 
extension study for up to 74 weeks
 The CIN-107 long term treatment effects on PD markers 
Endpoints: 
Primary Endpoints: 
The primary endpoints include the following: 
 
Safety parameters measured by adverse events (AEs), electrocardiograms (ECGs), hematology 
and chemistry laboratory values, vital signs, and physical examination 
 
Effectiveness measured by change in mean seated SBP after 12 weeks of treatment in patients 
with PA 
Secondary Endpoints: 
The secondary efficacy endpoints include the following: 
 
Effectiveness measured by change in mean seated DBP after 12 weeks of treatment in patients 
with PA 
 
The percentage of patients who achieve a seated BP response < 140/90 mmHg with CIN-107 
after treatment at each dose 
 
The percentage of patients who achieve a seated BP response < 130/80 mmHg with CIN-107 
after treatment at each dose 
 
The percentage of patients who, after 12 weeks of treatment with CIN-107 for PA, achieve 
either: 

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o
a plasma aldosterone concentration (PAC) < 15 ng/dL and a plasma renin activity 
(PRA)
0.5 ng/mL/h; or
o an ARR < 15; or 
o 
 
 
Exploratory Endpoints:
The exploratory endpoints include the following: 
 
Changes in the concentrations from baseline to end of treatment (EOT) in PD markers, 
including but not limited to, PAC, 11-deoxycorticosterone, PRA, direct renin concentration, 
calculated ARR, and 24-hour urinary aldosterone, NT-proBNP, sodium, and potassium with 
CIN-107 treatment 
 
Relationship between BP reduction and changes in aldosterone and renin levels and ARR with 
CIN-107, and as a function of CIN-107 dose  
Extension Part (Part 2) Additional Endpoints  
 
Safety parameters measured by adverse events (AEs), electrocardiograms (ECGs), hematology 
and chemistry laboratory values, vital signs, and physical examination for patients who elect to 
participate in the extension study for up to 74 weeks 
Inclusion Criteria 
Patients who meet all the following criteria will be eligible to participate:
1.
18 years of age 
2. Have been diagnosed with PA. The diagnosis may be based on meeting all three of the criteria 
of 1) elevated aldosterone level > 20 ng/dL (555 pmol/L), 2) plasma renin concentration (PRC) 
< lower limit of renin assay or plasma renin activity (PRA) < 1 ng/mL/min, and 3) 
hypokalemia (no confirmatory testing is needed in these cases). Otherwise, the diagnosis of PA 
must include BOTH:   
 
Historical evidence of plasma aldosterone to renin activity ratio (ARR) of > 15 
if the PRA was measured in ng/mL/hr or aldosterone to direct renin ratio 
(ADRR) > 50 if aldosterone was measured in pmol/L and direct renin 
concentration in mU/L (see protocol section 3.1.2 for conversion factors 
if needed to calculate ARR or ADRR), AND
 
Historical or newly conducted confirmatory testing by one of the following 
methods: the fludrocortisone-suppression test, the oral saline load test, the 
intravenous saline load test, or the captopril challenge test 
3. Are taking mineralocorticoid receptor antagonist (MRA) to control BP; or are newly 
diagnosed with PA and have not started MRA treatment 
Note: the MRAs can be taken with or without other antihypertensive agents including beta 
blockers, clonidine, methyldopa, minoxidil, angiotensin-converting enzyme inhibitors, 
diuretics, angiotensin receptor blockers, and/or dihydropyridine calcium channel blockers 
4. Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA 
5. Are willing to be compliant with the contraception and reproduction restrictions of the study as 
follows: 
a. Male patients must agree to abstain from sperm donation from Day 1 through 90 days 
after the final dose of study drug 
b. Postmenopausal women must not have had menstrual bleeding for at least 1 year 
before initial dosing and either be > 60 years or have an elevated follicle stimulating 
hormone level of > 40 mIU/mL at Screening 

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c.
Female patients of childbearing potential (i.e., ovulating, pre-menopausal, and not 
surgically sterile) must have a documented negative pregnancy test at Screening
d. Female patients of childbearing potential must use a highly effective method of 
contraception (i.e., <1% failure rate) from Day 1 through 30 days after the last 
administration of study drug. Acceptable methods of contraception include: 
i. Surgical sterilization (tubal ligation) 
ii. Intra-uterine device for at least 12 weeks prior to Screening Visit 
iii. Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 
weeks before the Screening Visit or 
iv. Diaphragm used in combination with spermicide 
6. Are willing and able to give informed consent for participation in the study 
7.
Have 
 160 mmHg after dosing of MRA 
treatment is ceased for up to 4 weeks duration
are newly diagnosed with PA and have not taken an MRA in the past 12 weeks 
Exclusion Criteria
Patients who meet any of the following criteria at Screening (Visit 1) will be excluded from 
participation in the study: 
1.
During the Screening, have a single occurrence of mean seated SBP > 180 mmHg or DBP 
> 110 mmHg if not taking an MRA; or have a 
 
 100 
mmHg if currently taking an MRA 
Note: Mean seated BP is defined as the average of 3 measurements obtained at any 1 clinical 
site visit. If the patient missed regularly scheduled antihypertensive medication(s) prior to the 
visit, and in the opinion of the Investigator has been otherwise adherent to their 
antihypertensive regiment, 1 BP re-
 2 hours after taking medication(s) 
2. Have a body mass index > 45 kg/m2 at the Screening Visit 
3. Have an upper arm circumference < 7 or > 17 inches at the Screening Visit 
4. Have had a previous surgical intervention for an adrenal adenoma or have a planned adrenal 
carcinoma, adrenalectomy, renal nerve denervation, or adrenal ablative procedure during the 
course of the study  
Note: Patients who have had a procedure > 6 months prior to Screening but still have elevated 
PAC (> 15 ng/dL) and meet BP and other eligibly criteria may be considered 
5. Have a documented estimated glomerular filtration rate < 45 mL/min/1.73 m2 using the 
Chronic Kidney Disease Epidemiology equation at the Screening Visit 
6. Have a planned dialysis or kidney transplantation during the course of the study 
7. Have known documented New York Heart Association class III or IV chronic heart failure 
8. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary 
syndrome, or hospitalization for heart failure within 6 months before the Screening Visit 
9. Have known current severe left ventricular outflow obstruction, such as obstructive 
hypertrophic cardiomyopathy and/or severe aortic valvular disease, diagnosed from a prior 
echocardiogram 
10. Have a planned coronary revascularization (percutaneous coronary intervention [PCI] or 
coronary artery bypass graft [CABG]) or any major surgical procedure during the study 
11. Have had PCI, CABG, other major cardiac surgery (e.g., valve replacement), or peripheral 
arterial bypass surgery within 6 months before the Screening Visit 
12. Have chronic, permanent atrial fibrillation 
13. Have a history of, or currently experiencing, clinically significant arrhythmias as judged by the 
Investigator, including ventricular tachycardia, ventricular fibrillation, Torsades de pointes, 
and supraventricular arrhythmias. Patients with minor forms of ectopy (e.g., premature atrial 
contractions) are not excluded per Investigator discretion 
14. Have had a prior solid organ transplant or cell transplant 

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15. Are expected to receive or are receiving any of the exclusionary drugs such as strong inducers 
of cytochrome P450 3A, drugs known to prolong QT, and/or chronic use of NSAIDs or 
steroids within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug 
until the end of treatment 
Note: patients who are using medication(s) noted above at Screening who are willing to come 
off during the course of the study are allowed to participate 
16. Have a known hypersensitivity to CIN-107 or excipients in CIN-107 
17. Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen 
18. Have typical consumption of > 14 alcoholic drinks weekly  
Note: One drink of alcohol is equivalent to ½ pint of beer (285 mL), 1 glass of spirits (25 mL), 
or 1 glass of wine (125 mL) 
19. Have participated in another clinical study involving any investigational drug within 30 days 
prior to the Screening Visit, or plans to participate in another clinical study within 30 days of 
discontinuation of study drug 
20. Have received experimental therapy with a small molecule within 30 days of the Screening 
Visit or 5 half-lives, whichever is longer, or received experimental therapy with a large 
molecule within 90 days of the Screening Visit or 5 half-lives, whichever is longer 
21. Have been on night shifts at any time during the 4 weeks before the Screening Visit and/or 
plans to begin night shift at any time during Screening 
22. Is pregnant, breastfeeding, or planning to become pregnant during the study 
23. Is considered by the Investigator, after reviewing medical and psychiatric history, physical 
examination, and laboratory evaluations, to be unsuitable for any other reason that may either 
place the patient at increased risk during participation or interfere with the interpretation of the 
study outcomes 
At Visit 2 prior to enrollment: 
24. Mean seated SBP > 180 mmHg or DBP > 110 mmHg or has 2 consecutive occurrences of 
 
 100 mmHg. Note that for patients whose BP exceeds 
these values after stopping their MRA, they may receive rescue antihypertensive medications 
(which are not MRAs) to control their blood pressure and have their BP reassessed for 
eligibility. 
25. Have evidence of any of the following at Screening: 
a. White blood cell count > 15  109/L or absolute neutrophil count < 1  109/L 
b. Serum potassium < 2.5 mEq/L. Note: Patients with a serum potassium level below 
normal range may continue in the study if the Investigator elects to correct the serum 
potassium level with supplementation and offers to manage the condition 
c. Serum potassium >5.0 mEq/L 
d. Hemoglobin < 10.0 g/dL or anticipated initiation of erythropoietin-stimulating agents 
or planned transfusion within 2 months after the Screening Visit 
e. Serum aspartate aminotransferase or alanine aminotransferase >3  upper limit of 
normal (ULN) or 
f. Total bilirubin >2  ULN, unless due to Gilbert’s syndrome 
g. Uncontrolled diabetes with glycosylated hemoglobin > 9.5% at the Screening Visit 
 
Overall Study Design: 
This is a multicenter, open-label study in adult patients with PA to evaluate the effectiveness and safety 
of CIN-107 after up to 12 weeks of treatment (Part 1), and then for eligible, consenting patients follow 
patients in Part 2 for up to 74 weeks for evidence of long-term safety and tolerability. Twelve to 18 
patients with a confirmed diagnosis of PA will be enrolled at clinical sites in the United States. Patients 
will complete 14 visits over a period of approximately 74 weeks. Additional unscheduled visits may 
occur as per the Investigator’s discretion to manage BP and electrolyte balance during the study.

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Schedule of Visits for Study D6970C00001
Top Panel-Part 1 Only 
 
Bottom Panel-Part 1 + Part 2 (Extension) 
Number of participants: 
Twelve to 18 patients with a confirmed diagnosis of PA, who consent to participate in the study and 
meet the eligibility criteria, will be enrolled. 
CIN-107 Dosage and Administration:
At Visit 3, after eligibility is confirmed, pre-dose vital signs recorded, and safety and PD samples 
drawn, patients will be provided with an initial dose of CIN-107 and start once daily (QD) dosing of 
CIN-107 tablets at 2 mg. At Visit 4, CIN-107 dose may be up-titrated to 4 mg QD if the patient has 
tolerated dosing of CIN-107 at 2 mg and the BP records indicate minimal hypotension risk. The 
Investigator will contact the patient by phone approximately 7 days after the dose is up titrated and the 
laboratory results are available. CIN-107 dose may be down-titrated to 2 mg if the safety laboratory 
results indicate hyperkalemia or hyponatremia, or other abnormal safety laboratory findings suggest 
that the patient is not tolerating CIN-107 4 mg dosing. At Visit 5, CIN-107 dose may be up-titrated to 8 
mg QD if the patient has tolerated dosing of CIN-107 at 4 mg. CIN-107 dose may be down-titrated to 
the 2 mg initial dose or continued with 4 mg. The final CIN-107 dose level will be determined by the 
investigator based on the BP and safety laboratory values. Patients will be instructed to take 1, 2, or 4 
tablets, per day for dosing at 2, 4, or 8 mg, respectively, by mouth QD with or without food. After Visit 
7, for patients eligible and willing to proceed to the extension (Part 2), the patient will continue their 
dose level subject to titration based on the investigators discretion until Visit 13, when dosing in the 
extension part of the study stops. 
Study Drug:
CIN-107 tablets with 2 mg strength will be provided as white tablets in bottles of 32 tablets per bottle. 
The study drug will be stored at controlled room temperature of 20°C to 25°C (68°F to 77°F). 
Consistent with the United States Pharmacopeia references, excursions between 15°C to 30°C are 
allowed during storage. During transport, excursions up to 40°C permissible up to 1 week.
Safety: 
The safety of CIN-107 will be assessed from the time of informed consent until Visit 14 (Week 74). 
All safety endpoints will be summarized descriptively. The safety endpoints will include the following:

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Change from baseline in potassium levels and/or potassium supplementation requirements, 
with CIN-107 after 12 weeks of treatment in patients with PA 
 
Vital signs (heart rate, respiratory rate, body temperature), mean SBP, mean DBP, orthostatic 
vitals (standing BP and heart rate), physical examinations, electrocardiography, weight 
measurement, and clinical laboratory evaluations including standard safety chemistry panel, 
hematology, coagulation, and urinalysis 
 
Treatment-emergent adverse events (TEAEs) 
 
Treatment-emergent serious adverse events (SAEs) 
 
TEAEs leading to premature discontinuation of the study drug 
 
Treatment-emergent marked laboratory abnormalities 
 
Change in standing SBP and DBP (measured at the clinical site prior to administration of study 
drug) 
Safety will be reassessed by review of the above endpoints at the end of 74 weeks of treatment 
for patients who elect to participate in the extension part of the study (Part 2) 
Statistical Analyses 
General 
The following analysis populations are defined for the different types of data analyses, and additional 
analysis population(s) may be added in the Statistical Analysis Plan (SAP).  
 
Intent-to Treat Population (ITT): All patients enrolled in the study 
 
Per-Protocol Population: All patients in the ITT population who have a baseline value for the 
SBP assessment, have at least one post-dose value for the SBP assessment, and have no major 
protocol deviations that could potentially impact the primary efficacy endpoint  
 
Safety Population: All patients who receive at least 1 dose of study drug will be used for safety 
analysis  
 
PK Population: All patients in the ITT Population who have at least 1 quantifiable plasma 
concentration 
 
PD population: All patients in the ITT Population who have at least 1 quantifiable 
concentration of a PD variable 
 
Safety Analyses 
The Safety Population will be the primary population for the safety analysis. All safety endpoints will 
be summarized descriptively. The assessment of safety will be based primarily on the frequency of 
AEs, clinical laboratory assessments, vital signs, and 12-lead ECGs. Other safety data will be 
summarized as appropriate. Summary statistics at baseline, at each visit, and of changes from baseline 
to each visit for laboratory parameters, vital signs, and other safety measurements will be provided. 
The occurrence of significant abnormalities in change from baseline of laboratory values will be 
summarized. Physical examination data will be listed.  
Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities. TEAEs, defined as AEs that 
newly occur or worsen in severity during the treatment period, will be summarized by system organ 
class and preferred term. A list of patients with SAEs and those who discontinue from study treatment 
due to an AE will be provided.  
Pharmacokinetic Analysis 
Individual plasma concentration data for CIN-107 and any measured metabolite(s) will be listed and 
summarized by visit, timepoint, and CIN-107 dose level in the PK population. 
Pharmacodynamic Analysis
All PD variables will be summarized descriptively in the PD population.

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Pharmacokinetic/Pharmacodynamic Analysis
An attempt will be made to correlate plasma concentration data with measures of safety, PD, and/or 
efficacy. 
Interim Analysis 
No formal interim analysis is planned. A Data Review Committee (DRC) will be formed in order to 
conduct data reviews to assess safety and tolerability. Details related to the DRC responsibilities, 
authorities, and procedures will be documented in the DRC Charter.

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TABLE OF CONTENTS 
Signature Page............................................................................................................................... 2
Investigator Agreement................................................................................................................ 3
Synopsis .......................................................................................................................................... 4
Table of Contents........................................................................................................................ 12
List of Tables ............................................................................................................................... 15
List of Figures.............................................................................................................................. 15
List of Abbreviations .................................................................................................................. 16
1
Introduction ......................................................................................................................... 18
1.1
Overview of Preclinical Studies with CIN-107 ................................................................ 20
1.2
Overview of Clinical Studies with CIN-107 ..................................................................... 21
2
Study Objectives .................................................................................................................. 24
2.1
Primary Objectives............................................................................................................ 24
2.2
Secondary Objectives........................................................................................................ 24
2.3
Exploratory Objectives ..................................................................................................... 24
2.4
Pharmacokinetic-Pharmacodynamic Objectives .............................................................. 24
2.5
Benefit/Risk Assessment .................................................................................................. 25
2.5.1 
Potential Risks ............................................................................................................................... 25 
2.5.2 
Potential Benefit ............................................................................................................................ 26 
3
Study Description ................................................................................................................ 27
3.1
Summary of Study Design ................................................................................................ 27
3.1.1 
Study Visits ..................................................................................................................................... 27 
3.1.2 
Rationale for Study Design ............................................................................................................ 32 
4
Selection and Withdrawal of Patients................................................................................ 35
4.1
Inclusion Criteria .............................................................................................................. 35
4.2
Exclusion Criteria ............................................................................................................. 36
4.3
Screen Failures .................................................................................................................. 38
4.4
Withdrawal Criteria .......................................................................................................... 38
4.4.1 
Procedures for Replacement of Withdrawn Patients ..................................................................... 39 
4.5
Dose Suspension and Stopping Rules ............................................................................... 39
4.6
Dose Titration Criteria ...................................................................................................... 40
5
Study Treatments ................................................................................................................ 42
5.1
CIN-107 Dose Strengths................................................................................................... 42
5.2
Blinding............................................................................................................................. 42
5.3
Drug Supplies.................................................................................................................... 42
5.3.1 
Formulation and Packaging .......................................................................................................... 42 
5.3.2 
Study Drug Preparation and Dispensing ....................................................................................... 42 

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5.3.3 
Study Drug Administration ............................................................................................................ 42 
5.3.4 
Adherence to Treatment and Home Blood Pressure Monitoring................................................... 42 
5.3.5 
Storage and Accountability ............................................................................................................ 43 
5.4
Prior and Concomitant Medication................................................................................... 44
5.4.1 
Excluded Medications and/or Procedures ..................................................................................... 44 
5.4.2 
Allowed Medications ...................................................................................................................... 44 
5.4.3 
Documentation of Prior and Concomitant Medication Use .......................................................... 44 
6
Study Procedures and Assessments ................................................................................... 45
6.1
Informed Consent.............................................................................................................. 45
6.2
Screening and Baseline Procedures and Assessments (Visits 1 and 2) ............................ 45
6.3
Treatment Period (Visit 3 through End of Treatment)...................................................... 45
6.4
Follow-Up Visit ................................................................................................................ 46
7
Efficacy Assessments ........................................................................................................... 48
7.1
Primary Endpoints ............................................................................................................ 48
7.2
Secondary Endpoints ........................................................................................................ 48
7.3
Exploratory Endpoints ...................................................................................................... 48
8
Pharmacokinetic, Pharmacodynamic, and Pharmacogenomic Assessments................. 50
8.1
Pharmacokinetic Assessments .......................................................................................... 50
8.2
Pharmacodynamic Assessments ....................................................................................... 50
8.3
Pharmacogenomic Assessments ....................................................................................... 51
8.3.1 
Collection, Storage, and Destruction of Pharmacogenomic Samples ........................................... 51
9
Safety Assessments .............................................................................................................. 52
9.1
Safety Endpoints............................................................................................................... 52
9.2
Adverse Events ................................................................................................................. 52
9.2.1 
Adverse (Drug) Reaction ............................................................................................................... 53 
9.2.2 
Unexpected Adverse Drug Reaction .............................................................................................. 53 
9.2.3 
Assessment of Adverse Events by the Investigator ......................................................................... 53 
9.2.4 
Adverse Events of Special Interest ................................................................................................. 54
9.3
Serious Adverse Events .................................................................................................... 55
9.4
Serious Adverse Event Reporting – Procedures for Investigators .................................... 55
9.5
Overdose Reporting .......................................................................................................... 56
9.6
Safety Surveillance and Management of Serum Potassium Levels .................................. 56
9.7
Pregnancy Reporting ......................................................................................................... 57
9.8
Expedited Reporting ......................................................................................................... 57
9.9
Vital Signs and Blood Pressure Measurements ................................................................ 58
9.10
Clinical Laboratory Evaluations ....................................................................................... 59
9.11
Electrocardiograms ........................................................................................................... 60
9.12
Physical Examination........................................................................................................ 60
9.13
Height and Weight ............................................................................................................ 60
10
Statistics................................................................................................................................ 61

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10.1
Analysis Populations......................................................................................................... 61
10.2
Statistical Methods ............................................................................................................ 61
10.2.1 Efficacy Analysis ............................................................................................................................ 61
10.2.2 Safety Analysis ............................................................................................................................... 61 
10.2.3 Pharmacokinetic Analysis .............................................................................................................. 62 
10.2.4 Pharmacodynamic Analysis ........................................................................................................... 62 
10.2.5 Pharmacokinetic/Pharmacodynamic Analysis .............................................................................. 62 
10.2.6 Interim Analysis ............................................................................................................................. 62 
11
Data Management and Record Keeping ........................................................................... 63
11.1
Data Management ............................................................................................................. 63
11.1.1 Data Handling ............................................................................................................................... 63 
11.1.2 Computer Systems .......................................................................................................................... 63 
11.1.3 Data Entry ...................................................................................................................................... 63 
11.1.4 Medical Information Coding .......................................................................................................... 63 
11.1.5 Data Validation .............................................................................................................................. 63 
11.2
Record Keeping ................................................................................................................ 63
11.3
End of Study ..................................................................................................................... 64
12
Investigator Requirements and Quality Control.............................................................. 65
12.1
Ethical Conduct of the Study ............................................................................................ 65
12.2
Institutional Review Board ............................................................................................... 65
12.3
Informed Consent.............................................................................................................. 65
12.4
Study Monitoring Requirements....................................................................................... 66
12.5
Disclosure of Data............................................................................................................. 66
12.6
Retention of Records......................................................................................................... 66
12.7
Publication Policy............................................................................................................. 67
12.8
Financial Disclosure.......................................................................................................... 67
13
Study Administrative Information..................................................................................... 68
13.1
Protocol Amendments....................................................................................................... 68
13.2
Address List ...................................................................................................................... 68
13.2.1 Sponsor .......................................................................................................................................... 68 
13.2.2 Contract Research Organization ................................................................................................... 68 
13.2.3 Serious Adverse Event Reporting ................................................................................................... 68 
13.2.4 Biological Specimens ..................................................................................................................... 68 
13.2.5 Central Depot ................................................................................................................................ 69 
13.2.6 Central Pharmacy .......................................................................................................................... 69 
14
References............................................................................................................................. 70
15
Appendices ........................................................................................................................... 73
Appendix A: Schedule of EVENTS: --Week -5 to 14- NOTE: Visit 8/Week 14 is FOR 
patients only in part 1, not in the EXTENSION PHASE (see following pages for that 
schedule)............................................................................................................................... 73

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Schedule of Events Weeks 12-74 for Patients in the part 2 Extension................................... 76
Appendix B: Clinical Laboratory Analytes.............................................................................. 79
Appendix C: Electrocardiogram Alert Criteria Guidance..................................................... 80
Appendix D: Excluded Medications .......................................................................................... 81
 
LIST OF TABLES
Table 1
List of Pharmacodynamic Assessments ...................................................................... 50
Table 2
Clinical Laboratory Analytes...................................................................................... 59
Table 3
Examples of Excluded Medications............................................................................ 81
 
LIST OF FIGURES 
Figure 1 
Schedule of Visits for Study CIN-107-122 ................................................................. 27

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LIST OF ABBREVIATIONS 
Abbreviation or Specialist Term
Explanation 
ACTH
adrenocorticotropic hormone
AE
adverse event
AESI
adverse event of special interest 
ARR 
aldosterone-to-renin ratio
ASI
aldosterone synthase inhibitor
AUC
area under the concentration time curve
AUC0-inf
area under the concentration-time curve from time zero to infinity
AUC0-last
area under the concentration-time curve from time zero to last 
measurable concentration
BP
blood pressure
CABG 
coronary artery bypass graft
CFR
Code of Federal Regulations 
CLR
renal clearance 
Cmax
maximum plasma concentration 
CRA 
Clinical Research Associate
CYP 
cytochrome P450 
DBP 
diastolic blood pressure 
DRC 
Data Review Committee 
ECG 
electrocardiogram
eCRF 
electronic case report form
EDC 
electronic data capture
EIU
exposure in utero
EOT 
end of treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice
GLP
Good Laboratory Practice 
HbsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIV
human immunodeficiency virus
ICF
informed consent form
ICH 
International Council for Harmonisation
IRB
Institutional Review Board
ITT
Intent-to-Treat
MAD 
multiple-ascending dose 
MATE 
multidrug and toxin extrusion
MedDRA
Medical Dictionary for Regulatory Activities
MMRM 
Mixed Model Repeated Measures
MR
mineralocorticoid receptor 
MRA
mineralocorticoid receptor antagonist 
NSAID 
nonsteroidal anti-inflammatory drug
PA
primary aldosteronism 
PAC 
plasma aldosterone concentration 
PCI
percutaneous coronary intervention
PD
pharmacodynamic(s)
PK
pharmacokinetic(s) 
PRA 
plasma renin activity 

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Abbreviation or Specialist Term
Explanation 
QD
once daily
QTc
heart rate-corrected QT interval
QTcF
heart rate-corrected QT interval using Fridericia’s formula
RAAS
renin-angiotensin-aldosterone system
SAD 
single-ascending dose 
SAE
serious adverse event
SAP
Statistical Analysis Plan
SBP 
systolic blood pressure
SUSAR
suspected unexpected serious adverse reaction 
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
USP
United States Pharmacopeia

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1
INTRODUCTION 
Aldosterone is a hormone that has been implicated in a variety of cardiovascular and renal diseases. 
It is the principal mineralocorticoid in humans and is synthesized in the adrenal cortex by the 
enzyme aldosterone synthase. Aldosterone is a key component of the renin-angiotensin-
aldosterone system (RAAS) and acts as a critical regulator of fluid and electrolyte homeostasis 
through its agonism of the mineralocorticoid receptor (MR). Its effect on end organs has been 
shown to occur via its direct interaction with the MR (genomic effect) in addition to mechanisms 
independent of that direct interaction (non-genomic or non-receptor mediated effects) 
(Duprez 2007, Funder 2009, Sato 2004).  
The association between plasma aldosterone and long-term survival has been demonstrated in 
patients with congestive heart failure or acute myocardial infarction (Swedberg 1990, Latini 2004, 
Güder 2007, Beygui 2006), and in patients with coronary artery disease (Ivanes 2012). 
Furthermore, the Framingham Offspring Study suggests that plasma aldosterone concentration 
(PAC) in normotensive patients predicts subsequent increases in blood pressure (BP) and the 
development of hypertension (Vasan 2004). Therefore, directly inhibiting the synthesis of 
aldosterone represents a promising target for the reduction of BP and a mitigation of the genomic 
and non-genomic effects on end organ damage (Marney 2007). 
Primary aldosteronism (PA) represents a group of disorders characterized by inappropriate 
production of aldosterone. The secretion of aldosterone is independent of the normal feedback 
influences of renin, angiotensin II, and sodium. It is the most common cause of secondary 
hypertension, with an estimated prevalence > 5% in patients with hypertension and up to 15% to 
20% in patients with treatment-resistant hypertension (Fogari 2007, Calhoun 2002). PA is caused 
by unilateral or bilateral adrenal hyperplasia, an adrenal adenoma, and, in rare cases, an adrenal 
carcinoma. There is also a rare condition of inherited familial hyperaldosteronism (Funder 2016). 
Excess aldosterone in patients with PA promotes increased distal renal tubular resorption of 
sodium and water by the kidneys and also contributes to end organ damage. This can lead to the 
development of hypertension in association with suppression of plasma renin; increased potassium 
excretion can lead to hypokalemia (Wrenn 2020, Hundemer 2017). 
Patients with PA demonstrate increased cardiovascular morbidity and mortality compared to age- 
and sex-matched patients with essential hypertension with the same degree of BP elevation 
(Milliez 2005, Stowasser 2005, Monticone 2018). In patients with PA, the spectrum of end organ 
adverse effects associated with autonomous secretion of elevated levels of aldosterone include 
endothelial dysfunction, vascular remodeling, enhanced sympathetic outflow, and impaired 
baroreflex function. These patients also exhibit increased left ventricular dimensions, myocardial 
fibrosis, increased carotid intima-media thickness, and femoral pulse wave velocity. These effects 
increase the risk of cardiovascular events including coronary artery disease, myocardial infarction, 
heart failure, stroke, and atrial fibrillation (Milliez 2005, Stowasser 2005, Catena 2008, 
Born-Frontsberg 2009).

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Despite the consequences of excess aldosterone and the relative common prevalence of PA, its 
screening is often overlooked. As many general practitioners consider PA to be relatively rare, 
screening rates as low as 1% to 2% among hypertensive patients have been reported and may only 
be considered when a patient is hypokalemic and hypertensive (Rossi 2019, Mulatero 2016). The 
Primary Aldosteronism Prevalence in Hypertension study reported a rate of confirmed PA of 
11.2% in 1125 consecutive newly diagnosed hypertensive patients (Rossi 2006). However, in this 
study, over half of patients with an aldosterone-producing adenoma, and 82% with bilateral 
hyperplasia, were normokalemic. A retrospective evaluation from clinical centers across 5 
continents demonstrated that only 9% to 37% of patients with PA present with hypokalemia 
(Funder 2016, Mulatero 2004). Furthermore, many clinicians believe that PA patients can be
adequately managed in the same manner as patients with primary hypertension.
The goals of treatment in patients with PA involve both the normalization of BP and the 
neutralization of effects of pathologic aldosterone-mineralocorticoid interactions. By addressing 
these elements, the risk of long-term cardiovascular and renal damage is reduced.
Mineralocorticoid receptor antagonists (MRAs) are the recommended medical treatment of choice 
in patients with PA due to bilateral adrenal hyperplasia or those with unilateral 
hyperplasia/adenoma who are unable or unwilling to undergo laparoscopic adrenalectomy 
(Funder 2016). MRAs exert their action by competitively inhibiting the binding of aldosterone to 
MRs (Monticone 2018). 
Besides the activity of MRAs on the MR, these drugs also act as antagonists at the androgen 
receptor and agonists at the progesterone receptor. Consequently, men treated with MRAs may 
experience gynecomastia and erectile dysfunction, while women may present with menstrual 
irregularities (Manolis 2019). MRAs can also lead to a compensatory increase in aldosterone 
secretion, which enhances the non-MR-mediated effects of aldosterone, and affects tissues not 
entirely protected by MRAs such as the brain (Bomback 2007). Spironolactone (Aldactone®) is 
the only Food and Drug Administration (FDA)-approved MRA for the treatment of PA 
(Aldactone 2014 package insert). Eplerenone (Inspra®) is used off-label as the MRA of choice for 
men at some PA centers. Although eplerenone is more selective than spironolactone with fewer 
adverse effects, its BP-lowering effect is typically less than that of spironolactone.
By inhibiting the synthesis of aldosterone in patients with PA, CIN-107 provides an opportunity 
to treat the elevated BP as well as reduce the risks of aldosterone-mediated end organ effects.
One of the challenges that has affected the development of aldosterone synthase inhibitors (ASIs) 
has been the difficulty in selectively inhibiting aldosterone synthase without also reducing the 
-hydroxylase 
(cytochrome P450 [CYP]11B1), an enzyme that shares very high sequence similarity with 
aldosterone syn
-hydroxylase leads to suppression 
of cortisol levels and compromises stress and immunologic responses, adversely influencing some 
metabolic functions and possibly increasing mortality rates (Weldon 2019, Oelkers 1996, Wagner 

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1984a, Wagner 1984b). LCI699, an ASI, was evaluated in clinical trials by Novartis but was 
discontinued in both antihypertensive and PA indications due to lack of specificity for aldosterone 
synthase (Amar 2010). It has recently been approved for the treatment of Cushing’s Disease.
Baxdrostat (formerly CIN-107 or RO6836191) is a highly potent, selective, and competitive 
inhibitor of human aldosterone synthase (encoded by the cytochrome P450 [CYP]11B2 gene).
Baxdrostat was acquired from Roche Pharmaceuticals, Inc. (hereinafter Roche) by CinCor 
Pharma, Inc. (hereinafter CinCor). CinCor is a wholly owned subsidiary of the AstraZeneca group 
of companies. AstraZeneca is pursuing further clinical development of the compound. In 
nonclinical in vivo studies (primarily conducted in primates), CIN-107 lowered aldosterone levels 
significantly without affecting basal- or adrenocorticotropic hormone (ACTH)-induced cortisol 
levels over a wide dose range. The ability of CIN-107 to lower aldosterone without affecting 
cortisol was confirmed following administration of single oral doses in healthy subjects 
(Study WP28586) conducted by Roche (Clinical Trial NCT01995383) and in the multiple-
ascending dose (MAD) study (Study CIN-107-111) conducted by CinCor.
This study is designed to evaluate the BP and aldosterone lowering effects of CIN-107 in patients 
with PA. Patients will need to wash out the MRA drug (such as spironolactone) and monitor BP 
daily for up to 4 weeks prior to administration of study drug. Other antihypertensive agents 
including beta blockers, thiazide diuretics, clonidine, methyldopa, minoxidil, chronic nonsteroidal 
anti-inflammatory drugs (NSAIDS), angiotensin-converting enzyme inhibitors, angiotensin 
receptor blockers, and/or dihydropyridine calcium channel blockers may be continued. After 
establishing a rise in BP after MRA withdrawal, if applicable, and with other anti-hypertensives 
agents remaining stable, treatment with CIN-107 for 12 weeks will be initiated. 
1.1 
Overview of Preclinical Studies with CIN-107 
CIN-107 is a highly selective, potent, and competitive ASI. Its inhibition of human aldosterone 
synthase is 100-fold more potent than that of the closely related 11 -hydrolase (encoded by the 
CYP11B1 gene) (CIN-107 IB Version 4). 
Dose and exposure-dependent inhibition of aldosterone synthesis was confirmed in acute and sub-
chronic monkey models. In cynomolgus monkeys challenged with an injection of ACTH, CIN-
107 blocked aldosterone synthesis without interfering with cortisol levels (CIN-107 IB Version 4).
In rats and monkeys, hepatic metabolism was the primary clearance mechanism for CIN-107. 
Renal clearance did not appear to play a significant role in the disposition of CIN-107 (CIN-107 
IB Version 4).
The adrenal gland was the primarily affected tissue in both rats and monkeys. CIN-107 was well 
tolerated in cynomolgus monkeys up to 7 mg/kg/day for up to 4 weeks but was not well tolerated 
at 40 mg/kg/day. A mechanistic 4-week cynomolgus monkey study demonstrated dose-related 
hypertrophy of adrenal zona glomerulosa cells with increased thickness or expansion of the zona 
glomerulosa layer, increased aldosterone synthase (CYP11B2) immunostaining, lipid vacuolation, 

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apoptosis, and proliferation of zona glomerulosa cells. These pathological changes in the adrenal 
gland were ameliorated by electrolyte supplementation and angiotensin-converting enzyme 
inhibition, indicating that they were exaggerated pharmacological effects of and 
physiologic/adaptive responses to aldosterone inhibition (CIN-107 IB Version 4).
CIN-107 was not well tolerated at 50 mg/kg/day in a pilot dose range-finding study on embryo-
fetal development in Wistar rates. There was no evidence for a mutagenic, clastogenic, or 
aneugenic potential of CIN-107 (CIN-107 IB Version 4).  
In vitro cardiovascular safety was assessed in a manual Good Laboratory Practice (GLP) human 
ether à-go-go related gene assay. The concentration needed for 20% inhibition was > 150-fold 
above the free maximum plasma concentration (Cmax) expected to be efficacious in man (at 
10 mg once daily [QD] dose for the treatment of hypertension). This indicated a very low 
probability of any QT liability (CIN-107 IB Version 4). 
In a modified Irwin test and in a whole-body plethysmography study in male rats, single oral 
administrations of CIN-107 up to a dose of 50 mg/kg did not induce any adverse effects on the 
central nervous system or respiratory function. The no observed adverse effect level was 
considered to be  50 mg/kg CIN107 for both studies (CIN-107 IB Version 4).  
1.2
Overview of Clinical Studies with CIN-107
Five clinical pharmacology studies of CIN-107 have been conducted to date in healthy subjects: a 
single-ascending dose (SAD) study, a MAD study, a study to characterize the effect of food on the 
pharmacokinetics (PK) and to bridge the PK of the solution formulation of CIN-107 to the tablet 
formulation, a study to assess the effect of CIN-107 on PK of the multidrug and toxin extrusion 
(MATE) substrate metformin, and a PK study to evaluate the PK of CIN-107 in subjects with 
varying degrees of renal function.  
Results of the SAD study which investigated the safety, tolerability, PK, and pharmacodynamics 
(PD) of CIN-107 in healthy male volunteers (Study WP28586 NCT01995383) demonstrated that 
single oral doses of CIN-107 up to 360 mg were well tolerated. There were no deaths, serious 
adverse events (SAEs), or dose-limiting events, and the maximum tolerated dose observed was at 
the highest dose tested of 360 mg (CIN-107 IB Version). 
Following oral administration, CIN-107 was rapidly absorbed with a median time to Cmax typically 
observed between 0.5 and 2 hours. A second, generally lower peak was often observed at 3 to 
4 hours post-dose. Thereafter, concentrations declined from peak in a biphasic manner with a long 
median terminal elimination half-life of approximately 25 to 31 hours. Over the anticipated 
therapeutically relevant dose range (through 10 mg), peak and overall exposures (as assessed by 
Cmax and area under the concentration time curve [AUC]) increased in a generally dose 
proportional manner (CIN-107 IB Version 4). 
Single doses of CIN-107 reduced plasma and urine aldosterone levels by approximately 85% to 
90% in a dose-dependent manner. A maximum effect on aldosterone reduction was consistently 

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achieved at a dose of 10 mg CIN-107 under the different conditions tested (Cortrosyn® challenge, 
standing, normal-salt diet, and low-salt diet conditions). No change in plasma cortisol levels after 
the Cortrosyn challenge was apparent across the full dose range tested (0 to 360 mg CIN-107). 
Although there was no effect on cortisol levels through 360 mg, some partial inhibition of the 
CYP11B1 enzyme at exposures well above those considered to be therapeutically relevant may 
have occurred based on observed increases in 11-deoxycortisol (at doses of 180 and 360 mg) and 
11-deoxycorticosterone (at doses  90 mg).  
Single oral doses of up to 360 mg CIN-107 did not affect serum electrolyte (chloride, potassium, 
sodium, and phosphate) levels, with no difference for subjects on active treatment versus those on 
placebo. Urine sodium and the sodium to potassium ratio both increased, with the sodium loss in 
urine greater than the potassium retention. No change in urine creatinine was apparent.  
Results of the MAD study indicate that multiple ascending doses of CIN-107 up to 5 mg QD for 
10 days were well tolerated by healthy subjects under low-salt (2.5 and 5 mg) and normal-salt 
conditions (0.5, 1.5, and 2.5 mg). Specifically, there were no deaths, SAEs, or treatment-emergent 
adverse events (TEAEs) leading to withdrawal, and there were no clinically significant changes in 
electrocardiograms (ECGs), or vital signs. PK data from the MAD study indicate that exposure to 
CIN-107 (as assessed by Cmax and AUC) is generally 2- to 2.5-fold higher at steady state as 
compared to that observed following a single dose. Exposures within the dose range studied 
increased in an approximately dose-proportional manner. PD data from this study confirmed the 
ability of CIN-107 to lower aldosterone at doses 
5 mg without affecting levels of cortisol or its 
precursor 11-deoxycortisol in healthy subjects. As expected with a reduction in aldosterone levels, 
there were mild, dose-dependent increases in plasma potassium levels and reductions in plasma 
sodium levels. 
Of note, the drug product used in the Phase 1 SAD and MAD studies was provided as an oral 
solution. As a replacement for the oral solution, a tablet formulation was developed and used in 
the Phase 1 Relative Bioavailability and Food Effect Study (CIN-107-112). The study was 
conducted with a 5 mg solution (fasted) and a 5 mg tablet (fed and fasted). Results of the relative 
bioavailability assessment indicate that exposure to CIN-107 and its primary metabolite following 
administration of the CIN-107 tablet formulation planned for use in future studies is equivalent to 
that observed following administration of the oral solution used in the SAD and MAD studies. 
Consumption of a high-fat, high-caloric meal had no substantial impact on the extent of absorption 
(as assessed by Cmax and AUC) but did have a small effect on the rate of absorption. Time to 
maximum plasma concentration occurred approximately 1 hour later (median of 4 hours) when 
CIN-107 was administered with the specified meal as compared to in a fasted state (median of 
3 hours). 
The metformin drug-drug interaction study demonstrated that systemic exposure to metformin is 
unchanged when administered with CIN-107. Specifically, the geometric mean ratio (associated 
90% confidence interval [CI]) for Cmax was 0.99 (0.91, 1.07) while the geometric mean ratios and 

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associated CI for AUC from time 0 to infinity (AUC0-inf) and AUC from time 0 to the last 
measurable concentration (AUC0-last) were 1.00 (0.94, 1.06) and 0.97 (0.91, 1.03), respectively. 
Consistent with the findings in plasma, CIN-107 did not affect renal clearance (CLR) of metformin 
(CLR = 27.99 L/h when metformin was administered alone and 26.48 L/h in the presence of CIN-
107). Furthermore, the safety profile of metformin was similar in the presence and absence of CIN-
107. Specifically, there were no deaths, SAEs, or TEAEs leading to withdrawal and there were no 
clinically significant changes in ECGs or vital signs. 
Study CIN-107-113 investigated the PK of CIN-107 in individuals with varying degrees of renal 
impairment. The PK profiles of CIN-107 and its primary metabolite CIN107-M, following 
administration of a single 10 mg dose in individuals with renal impairment, were qualitatively and 
quantitatively similar to those measured in healthy subjects. Pairwise comparisons of plasma PK 
parameters for CIN107 in the moderate to severe renal impairment group confirmed the lack of 
noteworthy effect across groups with geometric mean ratios of 1.02, 1.21, and 1.17 for Cmax, 
AUC0-inf, and AUC0-last, respectively, as compared to the control group. Higher exposures to CIN-
107 were not observed in the kidney failure group as compared to the control group with geometric 
mean ratios of 0.88, 0.68, and 0.68 for Cmax, AUC0-inf, and AUC0-last, respectively. The conclusions 
of these studies demonstrate that a single 10-mg dose of CIN-107 was well tolerated when 
administered to individuals with varying degrees of renal function, including those with moderate 
to severe renal impairment or kidney failure (on hemodialysis). There were no noteworthy 
increases in systemic exposure or decrease in clearance in individuals with impaired renal function. 
Dose adjustment of CIN-107 based on renal function was therefore not considered necessary. 
 

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2
STUDY OBJECTIVES
2.1 
Primary Objectives 
The primary objectives of Study D6970C00001 are to evaluate: 
 The safety and tolerability of CIN-107 in patients with PA at doses from 2 to 8 mg per 
day 
 The reduction in systolic blood pressure (SBP) with CIN-107 in patients with PA after 12 
weeks of treatment
2.2 
Secondary Objectives 
The secondary objectives of Study D6970C00001 are to evaluate:
 
The reduction in diastolic blood pressure (DBP) as a function of dose in patients with PA 
after 12 weeks of treatment 
 
The change in serum potassium and requirement for potassium supplementation as a 
function of CIN-107 dose 
2.3 
Exploratory Objectives 
Exploratory objectives are to evaluate:
 The correlation of serum aldosterone and plasma aldosterone-to-renin ratio (ARR) 
changes to drug dosage of CIN-107 
 Relationship between BP reduction and changes in aldosterone and renin levels with 
CIN-107 dosages 
 The changes in concentration in PD markers, including but not limited to: 
o plasma aldosterone and its relevant precursors (18-OH corticosterone, 
corticosterone, and 11-deoxycorticosterone) 
o plasma cortisol (free and total) and its relevant precursor  
o NT-pro (B-type natriuretic peptide) 
o plasma renin concentration and activity
o 24-hour urine analytes sodium, potassium, creatinine, albumin, protein, and 
aldosterone
2.4 
Pharmacokinetic-Pharmacodynamic Objectives 
The PK-PD objectives are to evaluate: 
 The exposure-response relationships of CIN-107 in patients with PA using measures of 
safety, effectiveness, and/or PD 
 
The relationship between plasma renin, aldosterone, and ARR to the SBP response to CIN-
107

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Extension Part (Part 2) Additional Objectives  
To assess: 
 
The safety and tolerability of CIN-107 in patients with PA at doses from 2 to 8 mg per day for 
patients who elect to participate in the extension study for up to 74 weeks
The management of blood pressure control for patients who elect to participate in the 
extension study for up to 74 weeks
The CIN-107 long term treatment effects on PD markers 
 
2.5 
Benefit/Risk Assessment 
2.5.1 Potential Risks 
2.5.1.1 
Cumulative Risk of Elevated Blood Pressure 
Wash out of MRA drugs increases the cumulative risk of elevated BP for patients participating in 
the study. To minimize this risk, patients will monitor BP closely and can start taking CIN-107 if 
has increased
rded at 
the Screening Visit, whichever occurs first. 
2.5.1.2 
Risk of Hyperkalemia and Hyponatremia 
Aldosterone leads to increased renal reabsorption of sodium and water together with secretion of 
potassium, thereby increasing blood volume and BP. Based on the preclinical observations and the 
mode of action for CIN-107, reduction of circulating aldosterone levels may lead to natriuresis and 
subsequently to increased serum potassium, decreased serum sodium, possible dehydration, and 
decreased BP. Potassium and sodium levels will be closely monitored in this study.
2.5.1.3 
Risk of Adrenal Effects 
While CIN-107 exhibits a highly selective CYP11B2 inhibition, CYP11B1 inhibition cannot be 
ruled out with repeat dosing and may result in reduction in cortisol levels, as seen with high doses 
in preclinical studies and in clinical studies of the non-selective CYP11B1/B2 inhibitor LCI699 
(Calhoun 2011, Andersen 2001, Karns 2013). Preliminary data from the CIN-107-121 study 
indicate no clinically meaningful effect of baxdrostat on plasma cortisol.
2.5.1.4 
Risk of Sex Hormone-Related Adverse Events 
Known side effects of MRAs including gynecomastia, mastodynia, and abnormal vaginal bleeding 
were observed more frequently with spironolactone than with eplerenone. Occurrence of these 
events will be monitored in this study. A selective inhibitor of aldosterone synthase is not expected 
to interfere with sexual hormone pathways (NCT01995383) as the MRA effects are believed to 
work through their off-target inhibition of other steroid hormone receptors, which is not a property 
expected to be present in an aldosterone synthase inhibitor. Preliminary data from the CIN-107-
121 study demonstrated no AEs such as those noted above that would indicate off target effects on 
sexual hormone pathways. 

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2.5.1.5 
Risk of Allergic Reactions 
Patients with known allergies to CIN-107 or its excipients should not receive CIN-107.
2.5.2 Potential Benefit 
CIN-107, an ASI, is a new therapeutic option aimed at decreasing aldosterone concentrations in 
plasma and tissues, thus reducing both MR-dependent and MR-independent effects of aldosterone. 
Patients enrolled in this study could benefit from the BP-lowering effect of CIN-107. Patient 
participation in the study will enable the assessment of a new therapeutic agent for the treatment 
of PA, with the potential to affect the clinical course of a large segment of the PA population.

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3
STUDY DESCRIPTION
3.1
Summary of Study Design 
This is a multicenter, open-label clinical pharmacology study in adult patients with PA to evaluate 
the effectiveness and safety of CIN-107 after up to 12 weeks of treatment. Twelve to 18 patients 
with a confirmed diagnosis of PA will be enrolled at clinical sites in the United States. Patients 
will complete 8 visits over a period of approximately 19 weeks. Additional unscheduled visits may 
occur as per the Investigator’s discretion to manage BP and electrolyte balance during the study.
The safety of CIN-107 will be assessed from the time of informed consent until the end of the 
Follow-Up Period. Patients will be followed for safety, effectiveness, and adherence throughout 
the study. PD variables analyzed during the study may include, but are not limited to, measures of 
aldosterone and its precursors, cortisol and its precursor, plasma renin activity (PRA), and 
calculation of ARR. PK variables analyzed during the study will include plasma concentrations of 
CIN-107 and any measured metabolite(s). 
Patients will be instructed to bring their antihypertensive medications and/or study drug and the 
BP monitoring device 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. 
3.1.1 Study Visits 
The study will consist of the following periods/visits detailed in Figure 1. 
Figure 1 
Schedule of Visits for Study D6970C00001 
Top Panel (Part 1 only) 
 
Bottom Panel Part 1 + Part 2 (Extension) 
 

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Abbreviations: MRA: mineralocorticoid receptor antagonist. 
Specifics of the treatment extension (optional part 2): 
1. Dose adjustment for baxdrostat allowed at week 12 and when clinically required during the treatment 
extension period 
2. Additional anti-hypertensive agents made be added in the extension period per Investigator’s judgment. 
3. For patients consented to participate in the treatment extension, MRA will not be permitted until 2 weeks 
after the last dose of baxdrostat is administered. 
 
3.1.1.1 
Screening Period 
Visit 1 (up to 5 weeks prior to date of first dose): 
Patients who have been diagnosed with PA and have signed the informed consent form (ICF) may 
complete the screening procedures. During the Screening Period, all assessments, safety, and 
administrative events will be completed as detailed in Appendix A.
Visit 2 (up to 4 weeks prior to date of first dose):
The patient’s eligibility will be confirmed and, if qualified, dosing with MRA (spironolactone or 
eplerenone) will be discontinued in those patients who are receiving an MRA. During the visit, 
an automated BP monitoring device will be provided to the patient. Training in the correct use of
the BP device and daily BP measurements thereafter will be required. Patients who take an MRA 
will discontinue the MRA and monitor BP daily for up to 4 weeks. 
Patients will be instructed to contact the Investigator and schedule Visit 3 as soon as possible 
(preferably within 1 week) if 
 160 
measurement recorded at the Screening Visit, whichever occurs first, or if symptoms of 
withdrawal (palpitations, chest pain, etc.) occur. Should patients observe a change in their blood 
pressure measurement that is cause for concern earlier than their planned, scheduled Visit 3, the
patient should contact the investigative site as soon as possible to determine the appropriate 
course of action. This may include an up-titration of current antihypertensive non-MRA 
medication or an addition of a new antihypertensive non-MRA medication in the short term to 
address any acute blood pressure concerns (Appendix D of the protocol outlines concomitant 
antihypertensive medications that can be used during the course of the study). Investigators may 
also expedite the Visit 3 in order to evaluate the patient and dispense study medication per their 
discretion.  However, for patients whose SBP > 180 mmHg or DBP > 110 mmHg or has 
2 consecutive occurrences of mean sea
 
 100 mmHg after stopping 
their MRA, they may undergo up titration of current antihypertensive medication or receive 
rescue antihypertensive medications (chosen at the discretion of the investigator, but which must 
not be MRAs) to control their blood pressure and have their BP reassessed for eligibility up to 
four weeks later. 
Any safety parameters should be checked as soon as possible in an unscheduled visit at the 
investigational site or in a local laboratory. For patients taking more than 1 anti-hypertensive 
agent, the other non-MRA agents should be taken continuously. Potassium supplements may be 
prescribed if clinically indicated. Unscheduled local laboratory assessments of electrolytes (see 

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Table 2, footnote b for specific values to be reported) may be done at the Investigator’s 
discretion to monitor the expected electrolyte level changes during the period after MRA 
discontinuation. These values should be entered in EDC.
If the SBP does not rise after 4 weeks, the patient will be considered a screen failure and will be 
advised to seek consultation with their physician for BP management.
For patients who are newly diagnosed with PA, have not taken any MRA in the past 12 weeks, 
-107 may start after all eligibility criteria are 
confirmed. Visit 2 is not required for these patients.  
3.1.1.2
Treatment Period
The treatment period will consist of 12 weeks of CIN-107 dosing. 
Visit 3 (Week 0, Day 1)
After eligibility is confirmed, pre-dose vital signs recorded, and safety and PD samples drawn, 
patients will be provided with an initial dose of CIN-107 and start once daily dosing of CIN-107 
tablets at 2 mg QD. 
Patients will be instructed to measure BP at least once every day prior to dosing with CIN-107 in 
the morning. The BP measurements should be the average of 3 readings. Patients should contact 
170/105 mmHg, if the patient experiences symptoms of hypotension, 
or the BP is < 90/60 mmHg. Safety surveillance will be conducted if clinically indicated. Up 
titrated doses of antihypertensive medications started after Visit 2 or rescue antihypertensive 
medications, if started, should be down titrated to baseline dose levels (or stopped if possible for 
the rescue medications) following Visit 3 and ideally by before any up-titration of baxdrostat doses
at Visit 4. Repeat and unscheduled testing for serum potassium may be measured at the clinical 
site or at local laboratory for a faster turn-around time to allow clinical assessment. 
Visit 4 (Week 4, Day 28)
CIN-107 dose may be up-titrated to 4 mg QD if the patient tolerates dosing of CIN-107 at 2 mg
(and if their background hypertensive medications are at the same doses as at screening) and the 
BP records indicate minimal hypotension risk. Blood and urine samples will be drawn for safety 
laboratory testing and for hormone level measurements including aldosterone and renin levels.
The Investigator will contact the patient by phone approximately 7 days after the dose is up-titrated 
and the laboratory results are available. CIN-107 dose may be down-titrated to 2 mg if the safety 
laboratory results indicate hyperkalemia, hyponatremia, or other abnormal safety laboratory 
findings suggesting that the patient is not tolerating CIN-107 4 mg dosing. An unscheduled visit 
may be conducted in the clinic or in local laboratory if clinically indicated or if samples cannot be 
processed.
Visit 5 (Week 8, Day 56)

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CIN-107 dose may be up-titrated to 8 mg QD if the patient has tolerated dosing of CIN-107 at 4 
mg. Up-titration should not proceed if the following occurs based on the most recent available 
laboratory results:
Hyperkalemia (ser
 Hyponatremia (serum sodium < 130 mmol/L)
 Un-
with systolic BP 
level < 120 mmHg 
 Hypotension (with 3 measurements of BP < 90/60 mmHg or symptomatic) 
CIN-107 dose may be down-titrated to the 2 mg initial dose or continued with 4 mg. The CIN-107 
dose level will be determined by the Investigator based on the BP and safety laboratory values. 
Visit 6 (Week 9, Day 63) 
Patients will have blood samples drawn for safety laboratory testing at the clinic or in a local 
setting if a patient lives far from the study investigational site approximately 1 week after the 8 mg 
dose is initiated. The visit should be scheduled early in the morning for measurement of morning 
cortisol and ACTH to monitor possible cortisol suppression. If cortisol insufficiency is suspected, 
the Investigator may also conduct an ACTH stimulation test. At the Investigator’s discretion, the 
dose may be down titrated to 4 mg or 2 mg if laboratory results indicate an electrolyte imbalance 
or other adverse reaction that is deemed related to CIN-107 treatment. Visit 6 is not required if a 
patient does not receive 8 mg dose of CIN-107. 
Visit 7 (Week 12, Day 89) 
For patients in Part 1 only, ie, not opting to continue in the extension part of the study, the patient 
will take the last dose at the clinic and return any unused study drug. Patients will be reminded 
that the BP must be measured daily, and the patient should contact the Investigator if the BP is 
 170/105 mmHg, if the patient experiences symptoms of hypotension, or if BP is < 90/60 mmHg. 
The treatment duration for patients who complete all 3 dose levels, and who opt not to continue in 
the extension part of the study, is 12 weeks. For patients who do not complete up-titration, the 
treatment duration will include at least 4 weeks of dosing with the final dose level. If down-titration 
of CIN-107 dose is determined at Visit 6 (Week 9), the total treatment duration may be extended 
to 13 weeks to allow sufficient time for CIN-107 treatment effect at the final dose to be assessed. 
If the final dose of CIN-107 is reached before week 8 (Visit 5) and no up-titration occurs at Visit 
5, the patients will be encouraged to continue CIN-107 treatment till Visit 7 for a total of 12 weeks 
of treatment. The patients who opt not to continue to Part 2 will not receive any study drug and 
will return for their safety follow up visit (Visit 8) in 2 weeks.  They may also resume their MRA 
at this time, per Investigator’s judgment.  
For patients who opt to continue in the extension part (Part 2) of the study, criteria for 
extension study eligibility include the following: 1) achieving at least comparable BP control to 
historical treatment, e.g., with mineralocorticoid receptor antagonist, prior to starting baxdrostat 
and 2) requiring potassium replacement while on baxdrostat that is less than or comparable to 

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historical replacement in patients with a history of hypokalemia. Exclusion criteria for the 
extension study are the same as for the main study. 
For eligible patients who opt to continue to the extension part of the study, patients will continue 
to receive their dose of baxdrostat and be instructed to measure BP at least once every week prior 
to dosing with CIN-107 in the morning, during the extension phase. The BP measurements should 
be 
 170/105 mmHg, 
if the patient experiences symptoms of hypotension, or the BP is < 90/60 mmHg. Safety 
surveillance will be conducted if clinically indicated. Repeat and unscheduled testing for serum 
potassium may be measured at the investigator’s clinical site--or at local laboratory for a faster 
turn-around time to allow clinical assessment. These patients entering part 2 will skip Visit 8 and 
their next visit will be Visit 9. 
 
3.1.1.3 
Safety Follow-Up Period 
The safety Follow-Up Period will last for approximately 2 weeks after the last dose of CIN-107. 
Patients will continue taking the non-MRA agents but will not start an MRA during the Follow-
Up Period so that the BP, safety data, and biomarker changes can be assessed after CIN-107 dosing 
is complete. MRA may be prescribed for safety reasons, if necessary, per Investigator’s discretion 
but every effort should be made to bring the patient back to collect the follow up study assessments 
off CIN-107 treatment, before initiating the MRA. 
Visit 8 (Week 14, Day 98) 
For patients not opting to continue in the extension part of the study, the patient will complete the 
last clinical visit and data for BP, samples for safety, and biomarker assessment samples will be 
collected. Patients will be counseled to maintain a healthy diet and lifestyle and resume MRA if 
clinically indicated. Patients will receive a telephone call from the clinical site 1-week (± 3 days) 
following the last dose of CIN-107 to assess adverse events and concomitant medications. 
For patients who opt to continue to the extension part of the study, Visit 8 can be skipped.
Visits 9-12 (Week 24, 36, 48, and 60)
For patients who opt to continue to the extension part of the study, patients will continue their dose 
of baxdrostat and be instructed to measure BP at least once every week prior to dosing with CIN-
107 in the morning. The BP measurements should be the average of 3 readings. Patients should 
170/105 mmHg, if the patient experiences symptoms of 
hypotension, or the BP is < 90/60 mmHg. Safety surveillance will be conducted if clinically 
indicated. Repeat and unscheduled testing for serum potassium may be measured at the clinical 
site or at local laboratory for a faster turn-around time to allow clinical assessment. At the 
Investigator’s discretion, the dose may be up or down titrated to between 2 mg or 8 mg daily if 
laboratory results indicate an electrolyte imbalance or other adverse reaction that is deemed related 
to CIN-107 treatment. 
Visit 13 (Week 72) 

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The patient in the extension phase of the study will take their last dose at the clinic and return any 
unused study drug. Patients will be reminded that the BP must be measured daily, and the patient 
170/105 mmHg, if the patient experiences symptoms 
of hypotension, or if BP is < 90/60 mmHg.
Visit 14 (Week 74) Safety Follow Up Period for Extension Part of the Study
For patients opting to continue in the extension part of the study, the patient will complete the last 
clinical visit and data for BP, samples for safety, and biomarker assessment samples will be 
collected. Patients will be counseled to maintain a healthy diet and lifestyle and resume MRA if 
clinically indicated. Patients will receive a telephone call from the clinical site 1-week (± 3 days) 
following the last dose of CIN-107 to assess adverse events and concomitant medications. 
 
3.1.2 Rationale for Study Design
PA is characterized by autonomous secretion of aldosterone from the zona glomerulosa of the 
adrenal cortex. ASIs, by inhibiting aldosterone synthesis, provide a direct mechanism to address 
the primary pathogenesis of the disease. Reducing aldosterone levels has the potential to reduce 
BP, either alone or in combination with other antihypertensive agents, improve potassium levels, 
and reduce the risk of end organ damage. CIN-107 is a highly potent, selective, and competitive 
inhibitor of aldosterone synthase. Based on findings from nonclinical studies and SAD and MAD 
clinical studies, CIN-107 may be a novel treatment for the deleterious effects of inappropriately 
elevated aldosterone resulting in elevated BP in patients with PA. CIN-107 has the potential to 
offer a new therapeutic option aimed at decreasing aldosterone concentrations in plasma and 
tissues, thus reducing both the mineralocorticoid receptor-dependent and mineralocorticoid 
receptor-independent effects of aldosterone.
The diagnosis of PA as defined for this this study reflects current guidelines (Funder JW, 2016). 
A diagnosis of PA is supported by meeting all three of the criteria of elevated aldosterone level (> 
20 ng/dL), depressed renin concentration or activity (PRC < lower limit of renin assay or PRA < 
1 ng/mL/min) and a history of hypokalemia. Patients who meet these criteria do not require 
confirmatory testing to meet the diagnosis of PA. Alternatively a PA diagnosis may be made via 
an aldosterone to direct renin ratio (ADRR) of > 50 if aldosterone was measured in pmol/L and 
direct renin concentration (DRC) is measured in mU/L. A conversion factor for DRC of 1 mIU (or 
1 mU)/L= 2.2 pg/mL and a conversion factor for aldosterone of 1 ng/dL to 27.7 pmol/L may be 
used. Plasma ARR of > 15 can be used as a component of the diagnosis of PA if the plasma renin 
activity was measured in ng/mL/hr and aldosterone in ng/dL. Exceeding the threshold of 15 for 
the ARR, or 50 for ADRR, still requires confirmatory testing by one of the methods outlined in 
the protocol. 

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3.1.2.1 
Dose Selection 
In a clinical study conducted in healthy subjects, administration of a single CIN-107 dose (1 to 
360 mg) induced a dose-dependent blunting of plasma aldosterone levels with a maximum effect 
achieved at the 10 mg dose level (approximate 85% to 90% decrease as compared to baseline). 
This effect was observed both on the ACTH challenge readout and on the standing aldosterone 
peak study (WP28586 Clinical Study Report). The ability of CIN-107 to inhibit aldosterone 
synthesis was confirmed in a multiple dosing study CIN-107-111. Markedly decreased aldosterone 
levels were observed after the initial dose of CIN-107 and were sustained throughout the 10-day 
-
107-111 Clinical Study Report). Based on the dose-dependent decreases in plasma aldosterone 
levels, it is hypothesized that CIN-107 dose at 0.5 mg per day may be effective in lowering 
aldosterone. The extent of aldosterone synthase inhibition was comparable between CIN-107 at 
2.5 mg and 5.0 mg in healthy subjects indicating the maximal treatment effect of CIN-107 is likely 
achieved in doses under 5 mg in subjects with regular or modestly elevated aldosterone. CIN-107 
dose strengths of 0.5, 1, 2, and 4 mg are being evaluated in patients with hypertension in the current 
phase 2 trials that CinCor is conducting. It is hypothesized that a higher dose level may be required 
in patients diagnosed with PA to suppress potential more significantly elevated aldosterone levels. 
The planned regimen of an initial dose of 2 mg with an up-titration option to 4 mg and 8 mg will 
allow the safety, tolerability, and effectiveness of CIN-107 be assessed. 
3.1.2.2 
Number of Patients 
A total of 12 to 18 patients with a confirmed diagnosis of PA, who consent to participate in the 
study and meet the eligibility criteria, will be enrolled. The study sample size is chosen empirically 
for the purpose of this study without considering any formal hypothesis testing. The selected 
sample size is considered adequate to meet the study objectives and support decision-making for 
future clinical studies.  
3.1.2.3 
Safety Measures 
Safety surveillance will be conducted at specified clinic visits from the time of informed consent 
until the end of the Follow-Up Period. The Investigator will review the BP records and measure 
vital signs and perform ECG and physical examination at designated visits. Safety laboratory tests 
including serum potassium, sodium, blood urea nitrogen, creatinine, bicarbonate levels, and ARR 
will be measured at the clinical site visit (See Schedule of Events Appendix A). 
Unscheduled assessments should be completed at the Investigator’s discretion for acute 
management of the patient (e.g., follow-up from elevated serum potassium, acute changes in 
clinical condition, suspected dehydration, etc.) as recommended below:
 
5.5 mEq/L and < 6 mEq/L, the patient should present to the 
clinical site immediately for repeat testing, but study drug dosing may continue.

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6 mEq/L, the patient should suspend study drug dosing and 
present to the clinical site immediately for repeat testing.
For serum sodium of < 130 mmol/L, the patient should present to the clinical site for 
repeat testing. The Investigator may withhold dosing if sodium is < 125 mmol/L.
For serum creatinine at 1.5 to 1.9 times the Screening levels or a 
0.3 mg/dL increase 
from levels at Screening, the patient should suspend study drug dosing and present to the 
clinical site for repeat testing.
Repeat and unscheduled testing for serum potassium and sodium levels may be measured at the 
local laboratory. For a full description of study procedures, assessments and visits see Section 6. 

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4
SELECTION AND WITHDRAWAL OF PATIENTS
4.1 
Inclusion Criteria 
Patients who meet all the following criteria will be eligible to participate: 
1. 
 18 years of age 
2. Have been diagnosed with PA. The diagnosis may be based on meeting all three of the criteria of 
1) elevated aldosterone level > 20 ng/dL (555 pmol/L), 2) plasma renin concentration (PRC) < 
lower limit of renin assay or plasma renin activity (PRA) < 1 ng/mL/min, and 3) hypokalemia (no 
confirmatory testing is needed in these cases). Otherwise, the diagnosis of PA must include both:   
 
Historical evidence of plasma aldosterone to renin activity ratio (ARR) of > 15 if 
the PRA was measured in ng/mL/hr or aldosterone to direct renin ratio 
(ADRR) > 50 if aldosterone was measured in pmol/L and direct renin 
concentration in mU/L (see protocol section 3.1.2 for conversion factors if 
needed to calculate ARR or ADRR), AND 
 
Historical or newly conducted confirmatory testing by one of the following 
methods: the fludrocortisone-suppression test, the oral saline load test, the 
intravenous saline load test, or the captopril challenge test 
3. Are taking MRA to control BP; or are newly diagnosed with PA and have not started MRA 
treatment
Note: the MRAs can be taken with or without other antihypertensive agents including beta 
blockers, clonidine, methyldopa, minoxidil, angiotensin-converting enzyme inhibitors, 
diuretics, angiotensin receptor blockers, and/or dihydropyridine calcium channel blockers
4. Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA 
5. Are willing to be compliant with the contraception and reproduction restrictions of the 
study as follows:
a.
Male patients must agree to abstain from sperm donation from Day 1 through 90 
days after the final dose of study drug
b. Postmenopausal women must not have had menstrual bleeding for at least 1 year 
before initial dosing and either be > 60 years or have an elevated follicle 
stimulating hormone level of > 40 mIU/mL at Screening
c. Female patients of childbearing potential (i.e., ovulating, pre-menopausal, and not 
surgically sterile) must have a documented negative pregnancy test at Screening 
d. Female patients of childbearing potential must use a highly effective method of 
contraception (i.e., <1% failure rate) from Day 1 through 30 days after the last 
administration of study drug. Acceptable methods of contraception include:
i. 
Surgical sterilization (tubal ligation)

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ii.
Intra-uterine device for at least 12 weeks prior to Screening Visit
iii.
Hormonal contraception (oral, implant, injection, ring, or patch) for at least 
12 weeks before the Screening Visit or
iv.
Diaphragm used in combination with spermicide
6. Are willing and able to give informed consent for participation in the study
7. Have increased SBP 
160 mmHg after dosing of MRA is 
not taken MRA in the past 12 weeks for managing hypertension 
4.2 
Exclusion Criteria 
Patients who meet any of the following criteria at Screening will be excluded from participation 
in the study: 
1. During the Screening, have a single occurrence of mean seated SBP > 180 mmHg or DBP 
> 
 160 mmHg or DBP 
 100 mmHg if currently taking an MRA 
Note: Mean seated BP is defined as the average of 3 measurements obtained at any 1 
clinical site visit. If the patient missed regularly scheduled antihypertensive medication(s) 
prior to the visit, and in the opinion of the Investigator has been otherwise adherent to their 
antihypertensive regiment, 1 BP re-
2 hours after taking medication(s)
2. Have a body mass index > 45 kg/m2 at the Screening Visit 
3. Have an upper arm circumference < 7 or > 17 inches at the Screening Visit 
4. Have had a previous surgical intervention for an adrenal adenoma or have a planned adrenal 
carcinoma, adrenalectomy, renal nerve denervation, or adrenal ablative procedure during
the course of the study
Note: Patients who have had a procedure > 6 months prior to Screening but still have 
elevated PAC (> 15 ng/dL) and meet BP and other eligibly criteria may be considered
5. Have a documented estimated glomerular filtration rate < 45 mL/min/1.73 m2 using the 
Chronic Kidney Disease Epidemiology equation at the Screening Visit 
6. Have a planned dialysis or kidney transplantation during the course of the study 
7. Have known documented New York Heart Association class III or IV chronic heart failure
8. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary 
syndrome, or hospitalization for heart failure within 6 months before the Screening Visit 
9. Have known current severe left ventricular outflow obstruction, such as obstructive 
hypertrophic cardiomyopathy and/or severe aortic valvular disease, diagnosed from a prior 
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10. Have a planned coronary revascularization (percutaneous coronary intervention [PCI] or 
coronary artery bypass graft [CABG]) or any major surgical procedure during the study
11. Have had PCI, CABG, other major cardiac surgery (e.g., valve replacement), or peripheral 
arterial bypass surgery within 6 months before the Screening Visit
12. Have chronic, permanent atrial fibrillation
13. Have a history of, or currently experiencing, clinically significant arrhythmias as judged 
by the Investigator, including ventricular tachycardia, ventricular fibrillation, Torsades de 
points, and supraventricular arrhythmias. Patients with minor forms of ectopy (e.g., 
premature atrial contractions) are not excluded per Investigator discretion 
14. Have had a prior solid organ transplant or cell transplant 
15. Are expected to receive or are receiving any of the exclusionary drugs such as strong 
inducers of cytochrome P450 3A, drugs known to prolong QT, and/or chronic use of 
NSAIDs or steroids within 28 days or 5 half-lives, whichever is longer prior to the first 
dose of study drug until the end of treatment 
Note: patients who are using medication(s) noted above at Screening who are willing to 
come off during the course of the study are allowed to participate 
16. Have a known hypersensitivity to CIN-107 or excipients in CIN-107 
17. Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen 
18. Have typical consumption of > 14 alcoholic drinks weekly  
Note: One drink of alcohol is equivalent to ½ pint of beer (285 mL), 1 glass of spirits 
(25 mL), or 1 glass of wine (125 mL) 
19. Have participated in another clinical study involving any investigational drug within 
30 days prior to the Screening Visit, or plans to participate in another clinical study within 
30 days of discontinuation of study drug 
20. Have received experimental therapy with a small molecule within 30 days of the Screening 
Visit or 5 half-lives, whichever is longer, or received experimental therapy with a large 
molecule within 90 days of the Screening Visit or 5 half-lives, whichever is longer 
21. Have been on night shifts at any time during the 4 weeks before the Screening Visit and/or 
plans to begin night shift at any time during Screening 
22. Is pregnant, breastfeeding, or planning to become pregnant during the study 
23. Is considered by the Investigator, after reviewing medical and psychiatric history, physical 
examination, and laboratory evaluations, to be unsuitable for any other reason that may 
either place the patient at increased risk during participation or interfere with the 
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At Visit 2 prior to enrollment:
24. Mean seated SBP > 180 mmHg or DBP > 110 mmHg or has 2 consecutive occurrences of 
 
 100 mmHg. Note that for patients whose BP 
exceeds these values after stopping their MRA, they may receive rescue antihypertensive 
medications (which must not be an MRA) to control their blood pressure and have their 
BP reassessed for eligibility.
25. Have evidence of any of the following at Screening:
a.
White blood cell count > 15 
109/L or absolute neutrophil count < 1  109/L
b. Serum potassium < 2.5 mEq/L. Note: Patients with a serum potassium level 
below normal range may continue in the study if the Investigator elects to correct 
the serum potassium level with supplementation and offers to manage the 
condition 
c.
Serum potassium >5.0 mEq/L
d. Hemoglobin < 10.0 g/dL or anticipated initiation of erythropoietin-stimulating 
agents or planned transfusion within 2 months after the Screening Visit 
e. Serum aspartate aminotransferase or alanine aminotransferase >3  upper limit of 
normal (ULN) or 
f. Total bilirubin >2  ULN, unless due to Gilbert’s syndrome 
g. Uncontrolled diabetes with glycosylated hemoglobin > 9.5% at the Screening 
Visit 
4.3
Screen Failures
Screen Failures are defined as patients who consent to participate in the clinical study but are not 
subsequently enrolled in the study and do not receive the first dose of study drug at Visit 3. 
Minimal information collected regarding Screen Failures includes, but is not limited to, 
demography, reason for screen failure, and any SAEs. 
4.4
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. The patient has a single occurrence of mean seated SBP > 180 mmHg or 
DBP > 110 mmHg OR 2 consecutive occurrences of mean seated SBP  160 mmHg or 
DBP
100 mmHg during the Treatment Period 
Note: If the patient missed the regularly scheduled antihypertensive medication(s) prior to 
the visit, 1 BP re-test is allowed 2 hours after taking the medication(s). Note the exception 
to this during the MRA washout period between Visit 2 and Visit 3 where rescue 
antihypertensive medications (that are not MRAs) can be used to reduce BP below these 
values. 

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3. The patient has an occurrence of any medical condition or circumstance that exposes the 
patient to substantial risk and/or does not allow the patient to adhere to the requirements 
of the protocol
4. The patient has a requirement of any prohibited concomitant medication
5. The patient becomes pregnant
6. The study is terminated by the Sponsor or the regulatory authority 
If a patient withdraws prematurely from the study due to the above criteria or any other reason, 
site staff should make every effort to complete the full panel of assessments scheduled for the End
of Treatment (EOT) Visit. The reason for patient withdrawal must be documented in the electronic 
case report form (eCRF). Patients should still attend study visits after Early Termination for safety 
monitoring unless the patient withdraws consent or is lost to follow-up. 
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 may be replaced (see Section 4.4.1). 
4.4.1 Procedures for Replacement of Withdrawn Patients 
Patients who discontinue from participation for reasons unrelated to safety, tolerability or due to 
an AE that is not considered to be related to the study drug may be replaced at the discretion of the 
Investigator in consultation with the Sponsor.  
Patients who discontinue for study drug-related safety or tolerability reasons will not be replaced.
4.5
Dose Suspension and Stopping Rules
The safety data of this open-label study will be monitored by the Investigators and the study 
Medical Monitor. In addition, a Data Review Committee (DRC) will evaluate emerging safety and 
efficacy data after approximately 6 and 12 patients complete the 12-week Treatment Period. 
Dosing of the study drug may be suspended temporarily for any of the following reasons. When 
one of the below criteria is met, the DRC will convene as soon as possible, preferably within 
48 hours, after learning of the occurrence of a criteria in order to determine if all active subjects 
should suspend dosing. 
1. Any SAE that is deemed related to the study drug, including death 
2. A study drug-related adverse event (AE) deemed by the Investigator to be severe in 
intensity (severity) in 
2 patients
3. A study drug-related AE from a single system organ class deemed to be of moderate 
intensity (severity) in 
4 patients
4. Serum potassium 
6 mEq/L; the patient should suspend study drug dosing and present to 
the clinical site immediately for repeat testing

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Note: This criterion is specific only to the individual patient suspending dosing. Other 
enrolled patients do not need to suspend dosing unless determined necessary by the DRC.
This is not an exhaustive list, and each instance should be evaluated on a case-by-case basis by the 
Investigator and Sponsor for restarting or discontinuing the study drug.
The Investigator, Sponsor and/or DRC may also suspend dosing for any other reason based on 
emerging data from this study or other ongoing CIN-107 studies. The DRC may review and discuss 
all available safety, PK, and PD data from all patients participating in the study up until the time 
of the event.  
When the below event occurs, the DRC does not need to convene (unless it meets one of the above-
mentioned criteria) but should be notified as soon as possible: 
 Dosing may be temporarily held in a patient who has evidence of hyponatremia (sodium 
concentrations < 130 mmol/L with repeat confirmation within 72 hours upon notification), 
or SBP 
 90 mmHg with symptoms consistent with postural hypotension until the 
respective hyponatremia or postural hypotension has resolved. The patient may restart 
study drug following consultation and approval from the Sponsor and/or Medical Monitor. 
Note: This criterion is specific only to the individual subject suspending dosing. Other 
enrolled subjects do not need to suspend dosing. 
4.6 
Dose Titration Criteria 
The Investigator will assess the daily BP records and determine if up-titration of CIN-107 dose 
may proceed without significant risk of hypotension at Visit 4 (4 weeks after the first dose) and at 
Visit 5 (8 weeks after the first dose). CIN-107 dose level may be up-titrated from the initial dose 
of 2 mg to 4 mg and from 4 mg to 8 mg at those visits.  
The Investigator or designated staff will contact the patient approximately 1 week after each dose 
adjustment by phone and assess if the BP changes are acceptable. The patient will be advised to 
have blood electrolytes or other safety laboratory tests performed locally for faster turn-around 
time if the patient experiences rapid BP change or symptoms suggesting other AEs. The dose may 
be reverted to a lower dose level if the patient experiences hyperkalemia, hyponatremia, or 
declining renal function based on laboratory testing or the SBP decreases rapidly to < 115 mmHg 
on 2 consecutive days.  
As described in Section 3.1.1.2, up-titration to 8 mg dose should not proceed if any one or more 
of the following occurs based on the most recent available laboratory results: 
 
 
Hyponatremia (serum sodium < 130 mmol/L) 
 Un-
 with systolic BP level < 120 mmHg 
 Hypotension (with 3 measurements of BP < 90/60 mmHg or symptomatic) 

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At Visit 6, approximately 1 week after the dosing of 8 mg is initiated, all patients will have blood 
samples drawn for safety laboratory testing at the clinic or in a local setting if a patient lives far 
from the study investigational site. At the Investigator’s discretion, the dose may be titrated down 
to 4 mg or 2 mg if the laboratory results indicate an electrolyte imbalance. Any of the dose changes 
and reasons for the dose adjustment must be recorded in the eCRF.

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5
STUDY TREATMENTS
5.1
CIN-107 Dose Strengths
The CIN-107 doses to be tested in this study are 2, 4, and 8 mg.  
5.2 
Blinding 
This is an open-label study. There is no blinding of study drug.  
5.3 
Drug Supplies 
5.3.1 Formulation and Packaging 
CIN-107 tablets with 2 mg strength will be provided as white tablets in bottles containing 32 tablets 
per bottle. CIN-107 tablets will contain the active ingredient and lactose anhydrous, 
microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium 
stearate as inactive ingredients.
5.3.2
Study Drug Preparation and Dispensing
The study drug will be delivered from the Central Depot to the clinical site. Once a patient has 
enrolled, site staff who have been delegated the task of drug dispensing by the Investigator will 
dispense the study drug (CIN-107) at Visits 3 (Day 1, first day of dosing), Visit 4, and Visit 5.
5.3.3
Study Drug Administration
Patients will be instructed to take 1, 2, or 4 tablets, per day for dosing at 2, 4, or 8 mg, respectively, 
by mouth QD with or without food.
Patients will be allowed a normal diet the morning of study drug administration. At Visit 3, patients 
will self-administer the first single dose of study drug at the clinical site. Subsequent doses of the 
study drug are to be taken by the patient QD by mouth at approximately the same time each 
morning at home.
On days of clinical site visits, patients will take their morning dose of applicable antihypertensive 
drugs (including medications for other comorbidities, if any) at home prior to their scheduled visit 
and withhold the study drug. At the clinical site, patients will self-administer the study drug to be 
witnessed by site staff after completion of pre-dose evaluations and laboratory sampling.
A tablet administration guide outlining the best practices for administering study drug will be 
provided to clinical sites.
5.3.4
Adherence to Treatment and Home Blood Pressure Monitoring
Patients will self-administer the study drug at the clinical site to be witnessed by site staff after 
completion of pre-dose evaluations and laboratory sampling; the date and time of study drug 
administration will be recorded.

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On days of clinical site visits, patients will bring their medications (study drug and all 
antihypertensive medications, if applicable) to the clinical site for assessment of treatment 
adherence. Site staff will assess treatment adherence based on pill counts. Site staff will also collect 
information from the patient about delays with taking the study drug and missed study drug doses 
over the 3 days prior to PK sampling and record the information in source files and eCRF.
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 (if applicable). Patients will record whether the daily dose(s) of study drug and each 
background antihypertensive medication (if applicable) were self-administered in a patient diary. 
Between clinical site visits, site staff will utilize the information recorded in the diary to ensure 
patient’s adherence to study drug and background antihypertensive regimen (if applicable). 
Home BP measurements will also be recorded in the daily diary by the patient. Patients will be 
asked to bring their daily diary to all clinical site visits for review by the Investigator/site staff. 
Site staff will counsel patients about the importance of adhering to their medications 
(antihypertensive regimen, if applicable, and/or study drug) with completion of diary entry every 
evening and from Visit 1, about home BP monitoring with entry of all BP measurements in their 
daily diary 
5.3.5 Storage and Accountability 
The study drug will be stored at controlled room temperature of 20 C to 25 C (68 F to 77 F). 
Consistent with the United States Pharmacopeia (USP) references, excursions between 15 C to 
30 C are allowed during storage. During transport, excursions up to 40 C permissible up to 
1 week. 
A drug accountability log will be maintained by the clinical sites indicating the receipt and 
dispensation of all study drug supplies. The log will indicate date dispensed, quantity dispensed, 
and the patient to whom the study drug was dispensed. 
At the conclusion of the study and after final accountability, all unused study drug should be 
collected by site staff and destroyed at the clinical site per the clinical site’s standard operating 
procedures. Clinical sites that do not allow destruction may return any unused study drug to the 
Central Depot for final drug accountability and destruction. It is the Investigator’s responsibility 
to ensure that the Sponsor has provided written authorization prior to return or destruction of the 
study drug, and that appropriate records of the disposal are documented and maintained. A 
certificate of return will be provided to the clinical sites by the Central Depot. If no study drug 
remains, this will be indicated in the drug accountability log. 

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5.4
Prior and Concomitant Medication
5.4.1
Excluded Medications and/or Procedures
Use of the following investigational, prescription, and/or over-the-counter medications is not 
permitted during the study:
Strong inducers of CYP3A
 Products known to prolong QT
 Chronic use of NSAIDs 
 Chronic use of steroids 
Examples of the above excluded products are provided in Appendix D. 
5.4.2 Allowed Medications 
Non-RAAS-modifying antihypertensive drug(s), defined as mono- or combination therapy with a 
non-dihydropyridine calcium channel blocker (e.g., diltiazem, verapamil), hydralazine, an alpha 
blocker, or a thiazide diuretic are allowed for BP management. MRAs or potassium sparing 
diuretics are not allowed during the CIN-107 treatment period. Anti-anginal nitrates, including 
nitroglycerine, isosorbide mononitrate, and isosorbide dinitrate are not considered 
antihypertensive agents. 
Medications other than those excluded (see Section 5.5.1) are also allowed during the study period. 
5.4.3 Documentation of Prior and Concomitant Medication Use 
All medications used within 30 days of the Screening Visit will be recorded. All concomitant 
medications and concurrent therapies will be documented in the patient’s eCRF as indicated in 
Appendix A. 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 
eCRF.
All concomitant medications and concurrent therapies (including fluids, electrolytes, vitamins, and 
supplements [including potassium supplements]), as well as “as needed” medications will be 
documented as indicated in Appendix A. 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 eCRF.

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6
STUDY PROCEDURES AND ASSESSMENTS
The activities at each clinic visit listed below are presented in Appendix A. The required laboratory 
tests scheduled at each visit are listed in Appendix B for the eligibility tests at screening and in 
Tables 1 and 2. Detailed laboratory assessments are described in Section 9.10. 
Visit 3 is the day of first dose and the basis for the visit window. A visit window of ± 3 days is 
allowed for visits after Visit 3.
6.1
Informed Consent
Written informed consent must be obtained from all patients before any protocol-specific 
procedures are performed.
Patients will be given the option to participate in a pharmacogenomic assessment during the 
consenting process. The written informed consent for pharmacogenomic sample collection will be 
included in the main ICF. For patients who provide written informed consent to participate in the 
optional pharmacogenomic assessment, a blood sample will be collected at any time during the 
Treatment Period. Section 12.3 provides additional details on informed consent.  
6.2
Screening and Baseline Procedures and Assessments (Visits 1 and 2) 
Screening procedures, including vital signs, BP measurements, and laboratory assessments, may 
be repeated no more than 2 times for eligibility purposes. A patient who is screened and does not 
meet the study Inclusion/Exclusion Criteria (Screen Failure) may be rescreened no less than 5 days 
after the last study visit, with Sponsor and/or Medical Monitor consultation and approval. 
At Visit 2, eligible patients who take an MRA to manage BP will discontinue dosing with MRA 
and monitor their BP daily for up to 4 weeks using the provided BP monitor.  
6.3 
Treatment Period (Visit 3 through End of Treatment)
After washout of MRA and when SBP is  160 mmHg or increases  20 mmHg from the 
measurement recorded at the Screening Visit, patients who continue to meet all the inclusion 
criteria and none of the exclusion criteria will be eligible to initiate study drug treatment (2 mg 
CIN-107) at Visit 3. During the treatment period, patients should take and record BP daily with 
the provided BP monitor. Patients will be instructed to contact the Investigator if BP is 
 170/105 mmHg, if the patient experiences symptoms of hypotension, or if BP is < 90/60 mmHg. 
All assessments and safety monitoring will occur as detailed in Appendix A (Schedule of Events).
At Visit 4 (Week 4), the dose of CIN-107 may be increased to 4 mg if the patient tolerates dosing 
of CIN-107 at 2 mg. The Investigator will contact the patient in approximately 7 days, when 
laboratory testing results are available, if safety laboratory results indicate hyperkalemia or 
hyponatremia. The dose of CIN-107 may remain at 2 mg if an electrolyte imbalance or other safety 
laboratory results indicate the patient is not tolerating CIN-107 dosing. 

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At Visit 5 (Week 8), the dose of CIN-107 may be increased to 8 mg if the patient tolerates dosing 
of CIN-107 at 4 mg. The Investigator will contact the patient if safety laboratory results indicate 
hyperkalemia or hyponatremia. The dose of CIN-107 may remain at 4 mg or reduced to 2 mg if an 
electrolyte imbalance or other safety laboratory results indicate the patient is not tolerating CIN-
107 dosing. Detailed dose titration guidance is described in Section 5.2.
At Visit 6 (Week 9), patients will have blood samples drawn for safety laboratory testing at the 
clinic or in a local setting if a patient lives far from the study investigational site approximately 
1 week after the highest dose of 8 mg is initiated. At the Investigator’s discretion, the dose may be 
down titrated to 4 mg or 2 mg if the laboratory results indicate an electrolyte imbalance. Visit 6 is 
not required if a patient does not receive 8 mg dose of CIN-107. 
At the Visit 7 (Week 12), all assessments, safety monitoring, collection of unused study drug, 
evaluation of treatment adherence, and administrative requirements will occur as detailed in the 
Schedule of Events (Appendix A). At Visit 7, for patients in Part 1 only, ie, not opting to continue 
in the extension part of the study, the patient will take the last dose at the clinic and return any 
unused study drug. Patients will be reminded that the BP must be measured daily, and the patient 
170/105 mmHg, if the patient experiences symptoms 
of hypotension, or if BP is < 90/60 mmHg. The patients who opt not to continue to Part 2 will not 
receive any study drug and will return for their safety follow up visit (Visit 8) in 2 weeks.  They 
may also resume their MRA at this time, per Investigator’s judgment.  
For patients who opt to continue in the extension part (Part 2) of the study, patients will continue 
to receive their dose of baxdrostat and be instructed to measure BP at least once every week prior 
to dosing with CIN-107 in the morning, during the extension phase. The BP measurements should 
be the average of 3 readings. Patients should contact the Investigator if the 
 170/105 mmHg, 
if the patient experiences symptoms of hypotension, or the BP is < 90/60 mmHg. Safety 
surveillance will be conducted if clinically indicated. Repeat and unscheduled testing for serum 
potassium may be measured at the investigator’s clinical site--or at local laboratory for a faster 
turn-around time to allow clinical assessment. These patients entering part 2 will skip Visit 8 and 
their next visit will be Visit 9.
6.4
Follow-Up Visit
At Visit 8 (Week 14), for patients not continuing in the extension (Part 2 of the study), all 
assessments, safety monitoring, collection of unused study drug, evaluation of treatment 
adherence, and administrative requirements will occur as detailed in the Schedule of Events 
(Appendix A).
At the Follow-Up Visit, concomitant medications will be recorded, and AEs will be recorded and 
assessed. Patients will be counseled to maintain a healthy diet and lifestyle and resume MRA at 
the same dose taken prior to washout if clinically indicated. For patients who have never taken an 
MRA, the dose may be titrated up based on Investigator’s judgement. For patients who opt to 
continue to the extension part of the study, Visit 8 can be skipped.

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Visits 9-12 (Week 24, 36, 48, and 60)
For patients who opt to continue to the extension part of the study, patients will continue their dose 
of baxdrostat and be instructed to measure BP at least once every week prior to dosing with CIN-
107 in the morning. The BP measurements should be the average of 3 readings. Patients should 
 170/105 mmHg, if the patient experiences symptoms of 
hypotension, or the BP is < 90/60 mmHg. Safety surveillance will be conducted if clinically 
indicated. Repeat and unscheduled testing for serum potassium may be measured at the clinical 
site or at local laboratory for a faster turn-around time to allow clinical assessment. At the 
Investigator’s discretion, the dose may be up or down titrated to between 2 mg or 8 mg daily if 
laboratory results indicate an electrolyte imbalance or other adverse reaction that is deemed related 
to CIN-107 treatment.
Visit 13 (Week 72)
The patient in the extension phase of the study will take their last dose at the clinic and return any 
unused study drug. Patients will be reminded that the BP must be measured daily, and the patient 
170/105 mmHg, if the patient experiences symptoms 
of hypotension, or if BP is < 90/60 mmHg.
Visit 14 (Week 74) Safety Follow Up Period for Extension Part of the Study 
For patients opting to continue in the extension part of the study, the patient will complete the last 
clinical visit and data for BP, samples for safety, and biomarker assessment samples will be 
collected, as detailed in the Schedule of Events (Appendix A). Patients will be counseled to 
maintain a healthy diet and lifestyle and resume MRA if clinically indicated. Patients will receive 
a telephone call from the clinical site 1-week (± 3 days) following the last dose of CIN-107 to 
assess adverse events and concomitant medications. 
 

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7
EFFICACY ASSESSMENTS
7.1
Primary Endpoints
The primary endpoints include the following:
 Safety parameters measured by AEs, ECGs, hematology and chemistry laboratory values, 
vital signs, and physical examination 
 Effectiveness measured by change in mean seated SBP after 12 weeks of treatment in 
patients with PA 
7.2 
Secondary Endpoints 
The secondary efficacy endpoints include the following: 
Effectiveness measured by change in mean seated DBP, after 12 weeks of treatment in 
patients with PA 
 The percentage of patients who achieve a seated BP response < 140/90 mmHg with CIN-
107 after treatment at each dose
 The percentage of patients who achieve a seated BP response < 130/80 mmHg with CIN-
107 after treatment at each dose
7.3
Exploratory Endpoints 
The exploratory endpoints include the following:
The exploratory endpoints include the following: 
 Changes in the concentrations from baseline to EOT in PD markers, including but not 
limited to, PAC, 11-deoxycorticosterone, PRA, direct renin concentration, calculated 
ARR, and 24-hour urinary aldosterone, NT-proBNP, sodium, and potassium with CIN-107 
treatment
o
Relationship between BP reduction and changes in aldosterone, renin levels and 
ARR with CIN-107
The percentage of patients who, after 12 weeks of treatment with CIN-107 for PA, achieve 
either:
o
a PAC < 15 ng/dL and a PRA 
0.5 ng/mL/h; or
o
an ARR < 15; or
o
unsuppressed renin activity PRA 1.0 ng/mL/h
Exploratory endpoints in extension study  
o The decline in systolic blood pressure at end of study versus baseline for patients 
who elect to participate in the extension study

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o
The decline in diastolic blood pressure at end of study versus baseline for patients 
who elect to participate in the extension study
o Change in the concentrations from baseline to end of the extension study participation
in PD markers, including but not limited to, PAC, 11-deoxycorticosterone, PRA, direct 
renin concentration, calculated ARR, and 24-hour urinary aldosterone, NT-proBNP, 
sodium, and potassium with CIN-107 treatment
o
Safety parameters measured by AEs, ECGs, hematology and chemistry laboratory 
values, vital signs, and physical examination throughout the extension study. 
 
 

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8
PHARMACOKINETIC, PHARMACODYNAMIC, AND PHARMACOGENOMIC 
ASSESSMENTS 
8.1
Pharmacokinetic Assessments
Pre- and post-dose PK samples will be collected within 15 minutes before study drug dosing at 
Visits 3, 4, 5, and 7 and at approximately 2 hours ± 5 minutes after study drug dosing. The actual 
date and time of collection of each PK sample will be recorded. 
Additional PK samples may also be collected in the event of an SAE, AE leading to withdrawal, 
or any other safety event at the discretion of the Investigator, DRC, and/or Sponsor, if needed for 
comparison with safety and tolerability data.
Samples will be analyzed to measure plasma concentrations of CIN-107 and any measured 
metabolites using validated liquid chromatography mass spectrometry methods. Analysis will be 
performed by Medpace Bioanalytical Laboratories, LLC.
Additional details regarding the PK sample collection, processing, and shipment can be found in 
the Laboratory Manual.
8.2 
Pharmacodynamic Assessments 
PD samplings, including blood at Visits 2, 3, 4, 5, 6, 7,8, 10 and 13 and 24-h urine collections at 
Visits 2, 4, 6,7, 10 and 13 will be performed. Site staff and patients will make every effort to time-
match PD blood sampling at each visit. Variables analyzed will include measurement of 
aldosterone and relevant precursors, cortisol and relevant precursor, plasma renin activity, direct 
renin concentration, and calculated aldosterone to renin ratio (see Table 2). The 24-h urine samples 
will be collected for measurements of aldosterone, electrolytes (potassium and sodium), creatinine, 
albumin and protein. Additional PD samples may also be collected in the event of an SAE, AE 
leading to withdrawal, or any other safety event at the discretion of the Investigator and/or Sponsor. 
The actual date and time of collection of each PD sample will be recorded. Details regarding the 
PD sample collection, processing, and shipment can be found in the Laboratory Manual
Table 1
List of Pharmacodynamic Assessments
Blood Analytes
 
Aldosterone and its relevant precursors (18 OH 
corticosterone, corticosterone, and 11-
deoxycorticosterone)
Cortisol (free and total) and its relevant precursor, 
11 deoxycortisol 
Direct renin concentration
Plasma renin activity 
NT-proBNP
ARR 
24-hour Urine Collection Analytes 
Aldosterone 
Potassium
Sodium 
Creatinine 
Albumin
Protein

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8.3
Pharmacogenomic Assessments
A single, optional, pharmacogenomic blood sample may be collected at any time during the 
patient’s participation in the Treatment Period of the study. The pharmacogenomic samples may 
be used for genetic research to explore the underlying causes of variability and/or differences in 
response in PK, PD, and/or safety data following administration of CIN-107.
Patients will be given the option to participate in the pharmacogenomic assessment during the 
consenting process. The written informed consent for pharmacogenomic sample collection will be 
included in the main ICF. For patients who provide written informed consent to participate in the 
optional pharmacogenomic assessment, a blood sample will be collected at any time during the 
patient’s participation in the Treatment Period. The patient may withdraw consent to participate in 
the pharmacogenomic assessment at any time during the study without withdrawing consent to 
participate in the study. See Section 8.3.1 for details regarding sample and data destruction 
following withdrawal of consent. 
The DNA sample will not be immortalized, sold to anyone, or submitted to a public genetic 
database. 
If analysis of the pharmacogenomic samples is undertaken, details of sample and data analyses 
will be provided in a separate protocol and/or analysis plan. The results obtained from analysis of 
the pharmacogenomic samples will be accessible to the Sponsor, the party(ies) performing sample 
analysis and data analyses, and the party involved in maintenance of the Sponsor’s database. The 
results may be disclosed to the Investigator but are not intended to be provided to the patient. The 
pharmacogenomic results will be reported or published without any of the patient’s personal 
identification information. Blood samples for pharmacogenomic assessments will be stored and 
analyzed at Cincinnati Children’s Hospital Medical Center. 
8.3.1 Collection, Storage, and Destruction of Pharmacogenomic Samples 
The date and time of the pharmacogenomic sample collection will be documented in the patient’s 
source documents. Each sample must be labeled with a unique identifier. GLP requires a chain of 
custody that is traceable to the sample donor. In order to ensure patient confidentiality, sample 
tubes will be identified only by patient identification number. 
Samples will be retained until exhausted or until the Sponsor requests destruction. 
If the patient withdraws consent, the blood samples will be promptly managed for proper 
disposition. However, the data will not be discarded if genetic analysis has been completed before 
the patient withdraws consent. 

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9
SAFETY ASSESSMENTS
9.1 
Safety Endpoints 
The safety of CIN-107 will be assessed from the time of informed consent until Visit 8 (Week 14). 
All safety endpoints will be summarized descriptively. The safety endpoints will include the 
following:
 Change from baseline in potassium levels and/or potassium supplementation 
requirements with CIN-107 after 12 weeks of treatment in patients with PA
 Vital signs (heart rate, respiratory rate, body temperature), mean SBP, mean DBP, 
orthostatic vitals (standing BP and heart rate), physical examinations, 
electrocardiography, weight measurement, and clinical laboratory evaluations including 
standard safety chemistry panel, hematology, coagulation, and urinalysis
 TEAEs
 Treatment-emergent SAEs 
 TEAEs leading to premature discontinuation of the study drug 
 Treatment-emergent marked laboratory abnormalities
 Change in standing SBP and DBP (measured at the clinical site prior to administration of 
study drug) 
9.2 
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. An AE can therefore be any unfavorable and/or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of the study drug, whether or not it is related to the study drug. All AEs, including observed 
or volunteered problems, complaints, or symptoms, are to be recorded on the appropriate eCRF.
AEs, which include clinical laboratory test variables, will be monitored and documented from the time 
of informed consent until the end of the Follow-up Period. Patients should be instructed to report any 
AE that they experience to the Investigator, whether or not they think the event is due to study drug. 
Beginning at Screening, Investigators should make an assessment for AEs at each visit and record the 
events on the appropriate AE eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (e.g., surgery, endoscopy, tooth extraction, 
or transfusion) should be recorded as an AE, not the procedure itself. 

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Any medical condition already present at the Screening Visit should be recorded as medical history 
and not be reported as an AE unless the medical condition or signs or symptoms present at baseline 
change in severity, frequency, or seriousness at any time during the study. In this case, it should 
be reported as an AE.
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study or are present at the Screening Visit and significantly worsen during the 
study should be reported as AEs, as described below. The Investigator will exercise his or her 
medical and scientific judgment in deciding whether an abnormal laboratory finding, or other 
abnormal assessment is clinically significant. Clinically significant abnormal laboratory values 
occurring during the clinical study will be followed until repeat tests return to normal, stabilize, or 
are no longer clinically significant. Abnormal test results that are determined to be an error should 
not be reported as an AE. Laboratory abnormalities or other abnormal clinical findings (e.g., ECG 
abnormalities) should be reported as an AE if any of the following are applicable: 
 If an intervention is required as a result of the abnormality 
 If action taken with the study drug is required as a result of the abnormality 
 Based on the clinical judgement of the Investigator 
AEs will be monitored and documented from the time of informed consent through Visit 8. 
Patients will be instructed to report any AE that they experience to the Investigator, regardless of 
whether they think the event is due to study treatment. Beginning at Screening and after 
collection of informed consent, Investigators should make an assessment for AEs at each study 
visit and record the event in the appropriate AE eCRF. 
9.2.1 Adverse (Drug) Reaction
All noxious and unintended responses to the study drug related to any dose should be considered 
an adverse drug reaction. “Responses” to the study drug means that a causal relationship between 
the study drug and an AE is at least a reasonable possibility (i.e., the relationship cannot be ruled 
out). 
9.2.2 Unexpected Adverse Drug Reaction
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information. 
9.2.3 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 as to its potential relationship to the study drug using the categories 
of yes or no. 
Assessment of Severity

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Mild – An event that is easily tolerated and generally not interfering with normal daily activities.
Moderate – An event that is sufficiently discomforting to interfere with normal daily activities.
Severe – An event that is incapacitating with inability to work or perform normal daily activities.
Assessment of Causality 
The relationship of an AE to the administration of the study drug is to be assessed according to the 
following definitions: 
No (unrelated, 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. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
The following factors should also be considered: 
 The temporal sequence from study drug administration 
Underlying, concomitant, intercurrent diseases 
Concomitant drugs 
Known response pattern for this class of study drug 
Exposure to physical and/or mental stresses 
The pharmacology and PK of the study drug 
9.2.4
Adverse Events of Special Interest
The Investigator will monitor each patient for clinical and laboratory evidence of pre-defined 
adverse events of special interest (AESIs) throughout the patient’s participation in this study. 
The Investigator will assess and record any additional information of the AESI in detail on an 
AE form which must be submitted within 24 hours of awareness of the event. 
For this study, AESIs include the following: 
Hypotension events that require clinical intervention 
Abnormal potassium laboratory values that require clinical intervention
Abnormal sodium laboratory values that require clinical intervention 

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During the course of the study, additional AESIs may be identified by the Sponsor. AESI must be 
recorded in the eCRF.
9.3
Serious Adverse Events
An AE or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, 
it results in any of the following outcomes: 
 Death 
 A life-threatening AE 
 Requires hospitalization or prolongation of existing hospitalization 
Note: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will 
not be recorded as a SAE under this criterion, nor will hospitalization for a procedure
scheduled or planned before signing of informed consent, or elective treatment of a pre-
existing condition that did not worsen from baseline. However, unexpected complications 
and/or prolongation of hospitalization that occur during elective surgery should be recorded 
as AEs and assessed for seriousness. Admission to the hospital for social or situational 
reasons (i.e., no place to stay, live too far away to come for hospital visits, respite care) 
will not be considered inpatient hospitalizations. 
 A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
 A congenital anomaly/birth defect 
 An important medical event 
Note: Important medical events that do not meet any of the above criteria may be considered an 
SAE when, based upon appropriate medical judgment, they may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the outcomes listed above. Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalizations, 
or the development of drug dependency. 
9.4
Serious Adverse Event Reporting – Procedures for Investigators
Initial Reports 
All SAEs occurring from the time of informed consent until 30 days following the last 
administration of study drug must be reported to Medpace Clinical Safety within 24 hours of the 
knowledge of the occurrence. After the 30-day reporting window, any SAE that the Investigator 
considers related to study drug must be reported to Medpace Clinical Safety or the 
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To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, Medpace Safety personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria and 
it is not possible to access the EDC system, send an e-mail to Medpace Safety at 
medpace-safetynotification@medpace.com or call the Medpace SAE reporting line, and 
fax/email the completed paper SAE form to Medpace (contact information listed in Section 13.2.3) 
within 24 hours of awareness. When the EDC system becomes available, the SAE information 
must be entered within 24 hours of the system becoming available. 
Follow-up Reports 
The Investigator must continue to follow 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.
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(e.g., patient discharge summary or autopsy reports) to Medpace Clinical Safety via fax or email. 
If it is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs. 
9.5
Overdose Reporting
Overdose refers to the administration of a quantity of the study drug given per administration or 
cumulatively (accidentally or intentionally), which is above the maximum recommended dose 
according to the protocol. 
In cases of a discrepancy in the drug accountability, overdose will be established only when it is 
clear that the patient has taken additional dose(s), or the Investigator has reason to suspect that the 
patient has taken additional dose(s). Clinical judgment should always be applied in determining 
overdose. 
All reports of overdose as described above must be reported on the Special Situations Report form 
and faxed/e-mailed to Medpace Clinical Safety (see Section 9.8) within 24 hours of knowledge of 
the event. All AEs associated with these Special Situation reports should be reported as AEs or 
SAEs as well as recorded on the AE eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome should be provided, when available. 
9.6
Safety Surveillance and Management of Serum Potassium Levels
Patients who present during the Screening Period (Visits 1 and 2) with a serum potassium level 
outside of the normal range may continue in the study if the Investigator elects to correct the serum 
potassium level with supplementation and offers to manage the condition. 
Serum potassium levels of patients will be monitored systematically throughout the study. In 
addition to the clinical laboratory tests predefined in the Schedule of Events (Appendix A), interim 

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assessments of serum potassium levels are recommended under certain situations (e.g., overdose 
of potassium supplements, vomiting and/or diarrhea for 
1 day) that may impact the patient’s 
electrolyte levels or fluid balance.
For serum potassium, 
5.5 mEq/L and < 6 mEq/L, the patient should present to the clinical site 
immediately for repeat testing and the study drug dosing need not be suspended.
For serum potassium,  6 mEq/L, the patient should suspend study drug dosing and present to the 
clinical site immediately for repeat testing.
Repeat and unscheduled testing for serum potassium should be measured at the local laboratory.
9.7
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 the study drug immediately and the patient 
should be withdrawn from the study. Early termination procedures should be implemented at that 
time. 
A pregnancy is not considered to be an AE or SAE; however, it must be reported to Medpace 
Clinical Safety within 24 hours of knowledge of the event. Medpace Clinical Safety will then 
provide the Investigator/clinical site the exposure in utero (EIU) form for completion. The 
Investigator/clinical site must complete the EIU form and fax/e-mail it back to Medpace Clinical 
Safety. 
If the female partner of a male patient becomes pregnant while the patient is receiving study drug 
or within the safety Follow-Up Period defined in the protocol, the Investigator should notify 
Medpace Clinical Safety as described above. 
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be completed and faxed/emailed to 
Medpace Clinical Safety. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
9.8 
Expedited Reporting 
Medpace will report all relevant information about Suspected Unexpected Serious Adverse 
Reactions (SUSARs) that are fatal or life-threatening as soon as possible to the FDA, and in any 
case no later than 7 days after knowledge by Medpace of such a case. Relevant follow-up 
information will subsequently be communicated within an additional 8 days. 
All other SUSARs will be reported to the FDA as soon as possible but within a maximum of 
15 days of first knowledge by Medpace. 
Medpace will also inform all Investigators as required per local regulations. The requirements 
above refer to the requirements relating to the study drug. 

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Safety Contact Information: Medpace Clinical Safety
Medpace SAE hotline – United States:
Telephone: +1-800-730-5779, dial 3 or +1-513-579-9911, dial 3
Fax: +1-866-336-5320 or +1-513-570-5196
Email: medpace-safetynotification@medpace.com
9.9
Vital Signs and Blood Pressure Measurements 
Vital signs will include heart rate, respiratory rate, and body temperature. Orthostatic vitals will 
include standing BP and heart rate. Vital signs and BP will be measured at visits as indicated in 
Appendix A using the following standardized procedures: 
Patients should not exercise, smoke, or consume caffeinated beverages or food for at least 
2 hours prior to each clinical site visit
At clinical site visits when study drug will be administered, vital signs and BP will be 
assessed pre-dose
Vital signs and BP measurements should be obtained prior to ECG recordings
 For measuring BP during clinical site visits, the following standardized procedures are 
recommended:
o
The patient should be seated for at least 5 minutes in the examination room with 
his/her back supported, feet flat on the floor, and the measurement arm supported 
so that the midpoint of the manometer cuff is at heart level
o
A designated AOBPM device will be provided to each clinical site and must be 
used for all study-related measurements
o
An appropriately sized cuff should be used with the bladder centered over the 
brachial artery
o
The cuff size and arm used for the measurement should be recorded
o
The arm with the higher mean seated BP value at Screening should be used for 
Screening and subsequent BP measurements
o
All BP measurements should be obtained at approximately the same time of day as 
the Screening measurements are obtained
o
Three seated BP measurements (each measurement 1 to 2 minutes apart) should be 
obtained using the same arm and the AOBPM device at each clinical site visit
o
If the lowest and highest SBP measurements are > 15 mmHg apart, additional 
readings should be performed

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o
Once the seated BP has been determined, the patient should be asked to stand, and 
a single standing BP measurement and heart rate (orthostatic vitals) will be obtained 
after 60 seconds, as required
9.10 Clinical Laboratory Evaluations
Safety laboratory tests include standard hematology, coagulation, and chemistry panel and
urinalysis. Clinical laboratory testing will take place at the local laboratory. See Table 2 for a full 
list of analytes. 
Table 2
Clinical Laboratory Analytes
Standard Safety Chemistry Panel 
Alanine aminotransferase
Albumin 
Alkaline phosphatase
Amylase 
Aspartate aminotransferase
Bicarbonate b
Blood urea nitrogen b
Calcium
Chloride b
Creatine kinase 
Creatinine b 
Estimated glomerular filtration rate b 
Gamma-glutamyl transferase 
Glucose b 
Inorganic phosphorus 
Lactate dehydrogenase
Lipase 
Potassium b
Sodium b
Total bilirubin 
Total protein 
Uric acid 
Additional Chemistry Parameters 
Glycosylated hemoglobin 
 
Hematology 
Hematocrit
Hemoglobin 
Platelets 
Red blood cell count
White blood cell count and differential a
 
Coagulation 
Activated partial thromboplastin time
Prothrombin time
International normalized ratio 
 
Urinalysis
Bilirubin 
Blood
Glucose 
Ketones 
Leukocyte esterase
Microscopy a 
Nitrite 
pH 
Protein
Specific gravity 
Urobilinogen
 
Endocrinology 
-human chorionic gonadotropin b
Follicle-stimulating hormone c 
a Manual microscopic review is performed only if white blood cell count and/or differential values are out of 
reference range. b Values typically measured/reported at a minimum for unscheduled electrolyte determinations. 
b Serum or point-of-care pregnancy tests will be performed only for female patients of childbearing potential 
(i.e., ovulating, pre-menopausal, and not surgically sterile). 
c Follicle-stimulating hormone levels will be measured only for female patients  60 years of age who are 
postmenopausal for at least 1 year at Screening and are not surgically sterile.  

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9.11 Electrocardiograms
Standard 12-lead ECGs will be performed at Visits 1, 3, 4, 5, 6, 7, and 8 (or Early Termination) as 
indicated in Appendix A. 
Every effort will be made to eliminate any sources of physical (including movement, eating, or 
drinking) or electrical interference. During these assessments, patients are not permitted to use cell 
phones, iPods, laptop computers, tablets, or any type of battery-operated or electrical device; all 
these devices must be turned off during the assessments. 
ECGs will be performed after the patient has been resting in the supine position for at least 
10 minutes. Twelve-lead ECGs will be printed and will be interpreted as soon as possible by a 
qualified Investigator (or sub-Investigator). All ECGs collected at the time of Screening, EOT, and 
Early Termination Visits must be evaluated for the presence of abnormalities by a qualified 
physician. 
Standard ECG parameters will be measured, and the following ECG parameters will be recorded: 
 Heart rate 
 QRS interval 
 PR interval 
 RR interval 
 QT interval 
 QTc (QTcF) 
Investigators should contact Medpace if any clinically meaningful changes from baseline are noted 
on review. See Appendix C for ECG alert criteria guidance. 
9.12 Physical Examination 
A complete physical examination will be performed at Visit 2 and includes assessment of general 
appearance, skin, head, eyes, ears, mouth, oropharynx, neck, heart, lungs, abdomen, extremities, 
and neuromuscular system. A limited physical examination will consist of a minimum of general 
appearance, skin, heart, lungs, and abdomen and will be performed at Visits 1, 3, and 7 (see 
Appendix A). 
9.13 Height and Weight 
Height will be measured at Visit 1 only and be taken with patient’s shoes off.  Weight will be 
determined at the specified visits throughout the study. 

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10 STATISTICS
10.1 Analysis Populations 
The following analysis populations are defined for the different types of data analyses, and 
additional analysis population(s) may be added in the Statistical Analysis Plan (SAP).  
 Intent-to Treat Population (ITT): All patients enrolled in the study
 Per-Protocol Population: All patients in the ITT population who have a baseline value for 
the SBP assessment, have at least one post-dose value for the SBP assessment, and have 
no major protocol deviations that could potentially impact the primary efficacy endpoint
 Safety Population: All patients who receive at least 1 dose of study drug will be used for 
safety analysis  
 PK Population: All patients in the ITT Population who have at least 1 quantifiable plasma 
concentration 
 PD population: All patients in the ITT Population who have at least 1 quantifiable 
concentration of a PD variable
10.2 Statistical Methods
10.2.1 Efficacy Analysis
The SAP will be finalized before database lock. Any changes to the methods described in the final 
SAP will be described and justified as needed in the Clinical Study Report.  
All study-collected data will be summarized using descriptive statistics, graphs, and/or raw data 
listings. Descriptive statistics for continuous variables will include the number of patients (n), 
mean, standard deviation, median, and minimum and maximum values. Analysis of categorical 
variables will include frequency and percentage. 
10.2.2 Safety Analysis 
The Safety Population will be the primary population for the safety analysis. All safety endpoints 
will be summarized descriptively.
The assessment of safety will be based primarily on the frequency of AEs, clinical laboratory 
assessments, vital signs, and 12-lead ECGs. Other safety data will be summarized as appropriate. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs, 
defined as AEs that newly occur or worsen in severity during the treatment period, will be 
summarized by system organ class and preferred term. A list of patients with SAEs and those who 
discontinue from study treatment due to an AE will be provided.  
Summary statistics at baseline, at each visit, and of changes from baseline to each visit for 
laboratory parameters, vital signs, and other safety measurements will be provided. The occurrence 

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of significant abnormalities in change from baseline of laboratory values will be summarized. 
Physical examination data will be listed. 
10.2.3 Pharmacokinetic Analysis
Individual plasma concentration data for CIN-107 and any measured metabolite(s) will be listed 
and summarized by visit, timepoint, and CIN-107 dose level in the PK population.
10.2.4 Pharmacodynamic Analysis
All PD variables will be summarized descriptively in the PD population. 
10.2.5  Pharmacokinetic/Pharmacodynamic Analysis 
An attempt will be made to correlate plasma concentration data with measures of safety, PD, and/or 
efficacy.  
10.2.6 Interim Analysis 
No formal interim analysis is planned. A DRC will be formed in order to conduct data reviews to 
assess safety and tolerability as outlined in Section 4.5. Details related to the DRC responsibilities, 
authorities, and procedures will be documented in the DRC Charter.

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11 DATA MANAGEMENT AND RECORD KEEPING
11.1 Data Management 
11.1.1 Data Handling 
Data will be recorded at the clinical site on eCRFs and reviewed by the Clinical Research Associate 
(CRA) during monitoring visits. The CRAs will verify data recorded in the EDC system with 
source documents. All corrections or changes made to any study data must be appropriately tracked 
in an audit trail in the EDC system. An eCRF will be considered complete when all missing, 
incorrect, and/or inconsistent data have been accounted for.
11.1.2 Computer Systems
Data will be processed using a validated computer system conforming to regulatory requirements.
11.1.3 Data Entry
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure username and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations 
(21 CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential.
11.1.4 Medical Information Coding 
For medical information, the following dictionaries will be used: 
 MedDRA for medical history and AEs and 
 World Health Organization Drug Dictionary for prior and concomitant medications 
11.1.5 Data Validation
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the clinical site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
11.2 Record Keeping 
Records of patients, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the clinical site. Source data are defined as all information in original 
records and certified copies of original records of clinical findings, observations, or other activities 
in a clinical study necessary for the evaluation and reconstruction of the clinical study. Source data 
are contained in source documents (original records or certified copies). These records will be 

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retained in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer 
or destruction of these records, the Sponsor must be notified in writing and be given the 
opportunity to further store such records.
11.3 End of Study
The end of the study or study completion is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last patient in the study.

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12 INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL
12.1 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 wellbeing 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.
12.2 Institutional Review Board
The Institutional Review Board (IRB) will review all appropriate study documentation in order to 
safeguard the rights, safety, and wellbeing of patients. The study will only be conducted at clinical 
sites where IRB approval has been obtained. The protocol, Investigator’s Brochure, ICF, 
advertisements (if applicable), written information given to the patients, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB by the 
Investigator.
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB prior to participation of patients in research studies. Prior to 
study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for patient 
recruitment, and any other written information regarding this study to be provided to a patient or 
patient’s legal guardian must be approved by the IRB. 
No drug will be released to the clinical site for dosing until written IRB authorization has been 
received by the Sponsor.
12.3 Informed Consent
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements.
The Investigator must ensure that each 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 was obtained prior to enrollment in the study. The original signed copy 
of the ICF must be maintained by the Investigator and is subject to inspection by a representative 
of the Sponsor, their representatives, auditors, the IRB, and/or regulatory agencies. A copy of the 
signed ICF will be given to the patient. 

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12.4 Study Monitoring Requirements
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, and applicable regulatory requirements, and that 
valid data are entered into the eCRFs.
To achieve this objective, the monitor’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well organized, and easily retrievable data. 
Before the enrollment of any patient in this study, the Sponsor or their designee will review with 
the Investigator and site personnel the following documents: protocol, Investigator’s Brochure, 
eCRFs and procedures for their completion, informed consent process, and the procedure for 
reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and the site staff will be expected to cooperate with the monitor 
and provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the clinical site by signature and date on the study-specific monitoring log.
12.5 Disclosure of Data
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Patients or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare.
Patient medical information obtained during the study is confidential and disclosure to third parties 
other than those noted above is prohibited. 
12.6 Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating patients (sufficient information to link 
records, e.g., eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE 
forms, source documents, and detailed records of treatment disposition. The records should be 
retained by the Investigator according to specifications in the ICH guidelines, local regulations, or 
as specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 

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If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor.
12.7 Publication Policy
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 Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 
12.8 Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 

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13 STUDY ADMINISTRATIVE INFORMATION
13.1 Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by Medpace or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB unless immediate implementation of the change is necessary for patient safety. In this case, 
the situation must be documented and reported to the IRB within 5 working days.
13.2 Address List
13.2.1 Sponsor
AstraZeneca AB 
Västra Mälarehamnen
SE-151 85 Södertälje, Sweden
Telephone: +46-8-553 260 00
 
13.2.2 Contract Research Organization
Medpace, Inc.
5375 Medpace Way
Cincinnati, OH 45227 
United States 
Telephone: +1-513-579-9911 
Fax: +1-513-579-0444 
13.2.3 Serious Adverse Event Reporting
Medpace Clinical Safety
Medpace SAE hotline – United States: 
Telephone: +1-800-730-5779, dial 3 or +1-513-579-9911, dial 3 
Fax: +1-866-336-5320 or +1-513-570-5196
E-mail: medpace-safetynotification@medpace.com
13.2.4 Biological Specimens
13.2.4.1 Central Laboratory 
Medpace Reference Laboratories, LLC 
5365 Medpace Way 
Cincinnati, OH 45227 
United States 
Telephone: +1-800-749-1737 or +1-513-366-3270
Fax: +1-513-366-3273

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13.2.4.2 Pharmacokinetic Laboratory 
Medpace Bioanalytical Laboratories, LLC
5365 Medpace Way
Cincinnati, OH 45227 
United States
Telephone: +1-800-730-5779 or +1-513-579-9911 
Fax: +1-513-579-0444 
13.2.4.3 Pharmacogenomic Laboratory 
Cincinnati Children's Hospital Medical Center
Attn: Discover Together Biobank
3333 Burnet Avenue 
Bldg. R, Rm 2530
Cincinnati, OH 45229 
United States
Telephone: +1-513-803-5166 
Fax: +1-513-636-4373 
13.2.5 Central Depot 
Clinigen Supplies Management, Inc.
300 Technology Dr  
Malvern, PA 19355 
United States 
Telephone: +1-215-596-4370 
Fax: +1-701-235-8014 
13.2.6 Central Pharmacy 
GoGoMeds 
Specialty Medical Drugstore, LLC 
525 Alexandria Pike, Suite 100 
Southgate, KY 41071 
United States 
Telephone: +1-888-795-5826 
Fax: +1-888-978-7947 

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14 References
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Andersen M, Bjerre P, Schrøder HD, et al. In vivo secretory potential and the effect of combination 
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Beygui F, Collet J-P, Benoliel J-J, et al. High plasma aldosterone levels on admission are 
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Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin 
Pract Nephrol. 2007;3(9):486-492. 
Born-Frontsberg E, Reincke M, Rump LC, et al. Cardiovascular and cerebrovascular comorbidities 
of hypokalemic and normokalemic primary aldosteronism: results of the German Conn’s Registry. 
J Clin Endocrinol Metab. 2009;94(4):1125-1130. 
Calhoun DA, Nishizaka MK, Zaman MA, et al. Hyperaldosteronism among Black and White 
subjects with resistant hypertension. Hypertension. 2002;40(6):892-896. 
Calhoun DA, White WB, Krum H, et al. Effects of a novel aldosterone synthase inhibitor for 
treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-
controlled phase 2 trial. Circulation. 2011;124(18):1945-1955. 
Catena C, Colussi G, Nadalini E, et al. Cardiovascular outcomes in patients with primary 
aldosteronism after treatment. Arch Intern Med. 2008:168(1):80-85. 
Duprez DA. Aldosterone and the vasculature: mechanisms mediating resistant hypertension. J Clin 
Hypertens (Greenwich). 2007;9(1 Suppl 1):13-18. 
Fogari R, Preti P, Zoppi A, et al. Prevalence of primary aldosteronism among unselected 
hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 
as a screening test. Hypertens Res. 2007;30(2):111-117. 
Funder JW. Reconsidering the roles of the mineralocorticoid receptor. Hypertension. 
2009;53(2):286-290. 
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. 

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Güder G, Bauersachs J, Frantz S, et al. Complementary and incremental mortality risk prediction 
by cortisol and aldosterone in chronic heart failure. Circulation. 2007;115(13):1754-1761.
Hundemer GL, Baudrand R, Brown JM, et al. Renin Phenotypes Characterize Vascular Disease, 
Autonomous Aldosteronism, and Mineralocorticoid Receptor Activity. J Clin Endocrinol Metab, 
June 2017;102(6):1835–1843.
Ivanes F, Susen S, Mouquet F, et al. Aldosterone, mortality, and acute ischaemic events in 
coronary artery disease patients outside the setting of acute myocardial infarction or heart failure. 
Eur Heart J. 2012;33(2):191-202. 
Karns AD, Bral JM, Hartman D, et al. Study of aldosterone synthase inhibition as an add-on 
therapy in resistant hypertension. J Clin Hypertens (Greenwich). 2013;15(3):186-192.
Latini R, Masson S, Anand I, et al. The comparative prognostic value of plasma neurohormones 
at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J. 2004;25(4):292-299. 
Manolis AA, Manolis TA, Melita H, et al. Eplerenone versus spironolactone in resistant 
hypertension: an efficacy and/or cost or just a men's issue? Curr Hypertens Rep. 2019;21(3):22. 
Marney AM, Brown NJ. Aldosterone and end-organ damage. Clin Sci (Lond). 2007;113(6):267-
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Milliez P, Girerd X, Plouin P-F, et al. Evidence for an increased rate of cardiovascular events in 
patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243-1248. 
Monticone S, D'Ascenzo F, Moretti C, et al. Cardiovascular events and target organ damage in 
primary aldosteronism compared with essential hypertension: a systematic review and meta-
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primary care physicians in Europe. J Hypertens. 2016;34(11):2253-2257. 
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Oelkers W. Adrenal insufficiency. N Engl J Med. 1996;335(16):1206-1212. 
Rossi GP. Primary Aldosteronism: JACC state-of-the-art review. J Am Coll Cardiol. 
2019;74(22):2799-2811. 
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Sato A, Saruta T. Aldosterone-induced organ damage: plasma aldosterone level and inappropriate 
salt status. Hypertens Res. 2004;27(5):303-310. 

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Stowasser M, Sharman J, Leano R, et al. Evidence for abnormal left ventricular structure and 
function in normotensive individuals with familial hyperaldosteronism type I. J Clin Endocrinol 
Metab. 2005;90(9):5070-5076.
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with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study 
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pharmacokinetics and pharmacodynamics of RO6836191 in healthy male volunteers. 
ClinicalTrails.gov. https://clinicaltrials.gov/ct2/show/NCT01995383. Accessed 09 July 2020. 
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Vasan RS, Evans JC, Larson MG, et al. Serum aldosterone and the incidence of hypertension in 
nonhypertensive persons. N Engl J Med. 2004;351(1):33-41. 
Wagner RL, White PF. Etomidate inhibits adrenocortical function in surgical patients. 
Anesthesiology. 1984;61(6):647-651. 
Wagner RL, White PF, Kan PB, et al. Inhibition of adrenal steroidogenesis by the anesthetic 
etomidate. N Engl J Med. 1984;310(22):1415-1421. 
Weldon SM, Brown NF. Inhibitors of aldosterone synthase. Vitam Horm. 2019;109:211-239. 
Wrenn SM, Vaidya A, Lubitz CC. Primary aldosteronism. Gland Surg. 2020;9(1):14-24. 
 

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15
APPENDICES
APPENDIX A: SCHEDULE OF EVENTS: --WEEK -5 TO 14- NOTE: VISIT 8/WEEK 14 IS FOR PATIENTS ONLY IN 
PART 1, NOT IN THE EXTENSION PHASE (SEE FOLLOWING PAGES FOR THAT SCHEDULE) 
Screening 
Treatment
Follow-up n
*Visit
1 
2
3 
4 l 
5 m
6
7
8 o
Study Day (visit window)
up to Day -
35 (+/- 3)
up to Day -
28 (+/- 3)
1 (+/- 3) 
28 (+/- 3)
56 (+/- 3)
63 (+/- 3) 
89 (+/- 3)
98 (+/- 3) 
Week
-5
-4
0
4
8
9
12
14
Mineralocorticoid Receptor Antagonist (MRA)a
MRA washout
X
MRA treatment
X
CIN-107 **
Dispense study drug
X
X
X
CIN-107 treatment b
 
X
X 
X
X
X 
 
Dose titration assessment 
 
X 
X
 
 
Unused study drug collection
X
Assess treatment adherence
 
X 
X
X
X 
 
Administrative
Informed consent
X
Eligibility
X
Demographics
X
Medical/surgical history
X
BP monitor dispensation and 
instructions c
X
Review of home BP monitoring
X
X
X
X
X
X
X
Assessments
Vital Signs e
X
X
X
X
X
X
X
X
Weight and Height (screening only)
X
X
X
X
X
X
X
X
Complete Physical Examination
X
Limited Physical Examination
X
X
X
12-Lead ECG
X
X
X
X
X
X
X

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Screening
Treatment
Follow-up n
*Visit
1
2
3
4 l
5 m
6
7
8 o
Study Day (visit window)
up to Day -
35 (+/- 3)
up to Day -
28 (+/- 3)
1 (+/- 3) 
28 (+/- 3)
56 (+/- 3)
63 (+/- 3) 
89 (+/- 3)
98 (+/- 3) 
Week
-5 
-4
0 
4
8
9
12 
14
Safety laboratory testing including 
urinalysis f, g
X
X
X
X
X
X
X
PD blood sampling h
X 
X
X 
X
X
X 
X
Provide 24-hour urine collection kit
X
X
X
X
PD urine sampling i
X 
X 
 
X
X 
 
PK blood sampling j 
 
X
X 
X
 
X 
 
HIV, HbsAg, HCV screen
X
 
 
 
 
 
Pregnancy test (WOCBP)
X
Follicle-stimulating hormone k
X
PGx sample (optional, once V3 to V7)  
X
Safety 
Adverse event monitoring
X
X
X
X
Prior/concomitant medications 
X
X 
X
X
Abbreviations: BP: blood pressure; ECG: electrocardiogram; HbsAg: hepatitis B surface antigen; HCV: hepatitis C virus; HIV: human immunodeficiency virus; 
PD: pharmacodynamic; PGx: pharmacogenomic; PK: pharmacokinetic; SBP: systolic blood pressure; WOCBP: women of childbearing potential.  
* Note: Patients should not exercise, smoke, or consume caffeinated beverages or food for at least 2 hours prior to each clinical study site visit. Additional 
unscheduled visits may occur at Investigator’s discretion to manage BP and electrolyte balance.  
** Note: If a patient is taking more than 1 anti-hypertensive agent, the other non-MRA agents should be taken continuously.
 
a Eligible patients that take an MRA to manage BP will discontinue MRA and monitor BP daily with provided BP monitor for up to 4 weeks before CIN-107 
dosing starts.  After the treatment period is complete, patients will resume the MRA after a 2-week Follow-Up Period is complete so that the BP, safety data, and 
biomarker changes can be assessed. The Follow-Up Period may be shortened and MRA may be prescribed, if necessary, due to safety concern per Investigator’s 
discretion. 
b Dosing with CIN-107 (2 mg
160 mmHg or the SBP increases by 20 mmHg, whichever 
is sooner. For patients who are newly diagnosed with PA, have never taken MRA for managing hypertension, 
-107 
may start after all eligibility criteria are confirmed. Visit 2 is not required for these patients. 
c 
170/105 mmHg, if the patient experiences symptoms of hypotension, or 
if BP is < 90/60 mmHg.  
d 24-hour urine collection will be analyzed for aldosterone, electrolytes (including but not limited to sodium and potassium), and albumin, protein, and creatinine. 
e Vital signs include heart rate (seated and standing), respiratory rate, body temperature, and BP (seated and standing).
f Safety laboratory tests include standard hematology, coagulation, chemistry panel and urinalysis. Full listing of laboratory analytes can be found in Table 2. 
g Safety laboratory testing may take place at local laboratory.

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h PD blood sample variables analyzed will include measurement of aldosterone and relevant precursors, cortisol and relevant precursor, plasma renin activity, 
direct renin concentration, calculated aldosterone to renin ratio and NT-proBNP. PD samples should be drawn prior to taking CIN-107.  
i PD 24-hour urine samples will be collected for measurements of aldosterone, electrolytes (potassium and sodium), creatinine, albumin and protein.
j PK variables analyzed will include plasma concentration of CIN-107 and any additional metabolites. Pre- and post-dose PK samples will be collected within 15 
minutes before study drug dosing at Visits 3, 4, 5, and 7 and 12 and at approximately 2 hours ± 5 minutes after study drug dosing.  
k  Follicle-stimulating hormone levels will be measured only for female patients 60 years of age who are postmenopausal for at least 1 year at Screening and are 
not surgically sterile  
l At Visit 4 (Week 4), CIN-107 dose may be increased to 4 mg if the patient tolerates dosing of CIN-107 at 2 mg. The Investigator will contact the patient by 
phone approximately 7 days after the dose is up-titrated and the laboratory results are available. CIN-107 dose may be down-titrated to 2 mg if the safety 
laboratory results indicate hyperkalemia, hyponatremia, or other abnormal safety laboratory findings suggest that the patient does not tolerate CIN-107 4 mg 
dosing.  
m At Visit 5 (Week 8), CIN-107 dose may be up-titrated to 8 mg QD if the patient tolerates dosing of CIN-107 at 4 mg. CIN-107 dose may be down-titrated to the 
2 mg initial dose or continued with 4 mg if the patient experiences hyperkalemia, hyponatremia, or signs and symptoms of hypotension or un-suppressed renin 
. The final CIN-107 dose level will be determined by the Investigator based on the BP and safety laboratory 
values. 
n During the safety follow-up period (approximately 2 weeks after the last dose of CIN-107), patients will continue taking the non-MRA agents but will not start 
the MRA so that the BP, safety data, and biomarker changes can be assessed after CIN-107 dosing. MRA may be prescribed, if necessary, per Investigator’s 
discretion. Patients will receive a telephone call from the clinical site 1-week (± 3 days) following the last dose of CIN-107 to assess adverse events and 
concomitant medications. 
o At Visit 8 (Week 14) [Visit 13 (week 74) in the extension phase)], patients will complete the last clinical visit and data for BP, samples for safety, and 
biomarker assessment samples will be collected. Patients will be counseled to maintain a healthy diet and lifestyle and resume MRA if clinically indicated.  

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SCHEDULE OF EVENTS WEEKS 12-74 FOR PATIENTS IN THE PART 2 EXTENSION
Extension Phase 
Follow-up n
*Visit
9 
10
11 
12
13
14
Study Day (visit window)
168 (+/- 7)
252(+/- 7)
336(+/-7)
420(+/-7)
504(+/-7)
532(+/-7)
Week
24
36
48 
60 
72
74 
Dispense study drug
X
X
X
X
X
CIN-107 treatment b
X
X
X
X 
X
Dose titration assessment 
X
X
X
X 
 
Unused study drug collection 
X
X
X
X 
X
Assess treatment adherence
X
X
X
X 
X
Eligibility p
X
 
 
Review of home BP monitoring
X
X
X
X 
X
X 
Vital Signs e
X
X
X
X
X
X
Weight
X
X
X
X
X
X
Complete Physical Examination
 
X
Limited Physical Examination
X
X
X
X
X
12-Lead ECG
X
 
X
X 
Safety laboratory testing including 
urinalysis f, g
X
X
X
X 
X
X 
PD blood sampling h
X
X
Provide 24-hour urine collection kit
X
X
PD urine sampling i
X
X
PK blood sampling j
X
Pregnancy test (WOCBP)
X
Safety
Adverse event monitoring
X
X
X
X
X
X
Prior/concomitant medications
X
X
X
X
X
X
MRA treatment
X

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Abbreviations: BP: blood pressure; ECG: electrocardiogram; HbsAg: hepatitis B surface antigen; HCV: hepatitis C virus; HIV: human immunodeficiency virus; 
PD: pharmacodynamic; PGx: pharmacogenomic; PK: pharmacokinetic; SBP: systolic blood pressure; WOCBP: women of childbearing potential.  
* Note: Patients should not exercise, smoke, or consume caffeinated beverages or food for at least 2 hours prior to each clinical study site visit. Additional 
unscheduled visits may occur at Investigator’s discretion to manage BP and electrolyte balance.  
** Note: If a patient is taking more than 1 anti-hypertensive agent, the other non-MRA agents should be taken continuously.
 
a Eligible patients that take an MRA to manage BP will discontinue MRA and monitor BP daily with provided BP monitor for up to 4 weeks before CIN-107 
dosing starts.  After the treatment period is complete, patients will resume the MRA after a 2-week Follow-Up Period is complete so that the BP, safety data, and 
biomarker changes can be assessed. The Follow-Up Period may be shortened and MRA may be prescribed, if necessary, due to safety concerns per Investigator’s 
discretion. 
b Dosing with CIN-
160 mmHg or the SBP increases by 20 mmHg, whichever 
mHg, dosing with CIN-107 
may start after all eligibility criteria are confirmed. Visit 2 is not required for these patients. 
c 
 170/105 mmHg, if the patient experiences symptoms of hypotension, or 
if BP is < 90/60 mmHg.  
d 24-hour urine collection will be analyzed for aldosterone, electrolytes (including but not limited to sodium and potassium), and albumin, protein, and creatinine. 
e Vital signs include heart rate (seated and standing), respiratory rate, body temperature, and BP (seated and standing). 
f Safety laboratory tests include standard hematology, coagulation, chemistry panel and urinalysis. Full listing of laboratory analytes can be found in Table 2.
g Safety laboratory testing may take place at local laboratory. 
h PD blood sample variables analyzed will include measurement of aldosterone and relevant precursors, cortisol and relevant precursor, plasma renin activity, 
direct renin concentration, calculated aldosterone to renin ratio and NT-proBNP. PD samples should be drawn prior to taking CIN-107.  
i PD 24-hour urine samples will be collected for measurements of aldosterone, electrolytes (potassium and sodium), creatinine, albumin and protein.
j PK variables analyzed will include plasma concentration of CIN-107 and any additional metabolites. Pre- and post-dose PK samples will be collected within 15 
minutes before study drug dosing at Visits 3, 4, 5, and 7 and 12 and at approximately 2 hours ± 5 minutes after study drug dosing.  
k  Follicle-stimulating hormone levels will be measured only for female patients 60 years of age who are postmenopausal for at least 1 year at Screening and are 
not surgically sterile  
l At Visit 4 (Week 4), CIN-107 dose may be increased to 4 mg if the patient tolerates dosing of CIN-107 at 2 mg. The Investigator will contact the patient by 
phone approximately 7 days after the dose is up-titrated and the laboratory results are available. CIN-107 dose may be down-titrated to 2 mg if the safety 
laboratory results indicate hyperkalemia, hyponatremia, or other abnormal safety laboratory findings suggest that the patient does not tolerate CIN-107 4 mg 
dosing.  
m At Visit 5 (Week 8), CIN-107 dose may be up-titrated to 8 mg QD if the patient tolerates dosing of CIN-107 at 4 mg. CIN-107 dose may be down-titrated to the 
2 mg initial dose or continued with 4 mg if the patient experiences hyperkalemia, hyponatremia, or signs and symptoms of hypotension or un-suppressed renin 
activity (plasma 
. The final CIN-107 dose level will be determined by the Investigator based on the BP and safety laboratory 
values. 
n During the safety follow-up period (approximately 2 weeks after the last dose of CIN-107), patients will continue taking the non-MRA agents but will not start 
the MRA so that the BP, safety data, and biomarker changes can be assessed after CIN-107 dosing. MRA may be prescribed, if necessary, per Investigator’s 
discretion. Patients will receive a telephone call from the clinical site 1-week (± 3 days) following the last dose of CIN-107 to assess adverse events and 
concomitant medications. 
o At Visit 8 (Week 14) [Visit 13 (week 74) in the extension phase)], patients will complete the last clinical visit and data for BP, samples for safety, and 
biomarker assessment samples will be collected. Patients will be counseled to maintain a healthy diet and lifestyle and resume MRA if clinically indicated. 

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p Eligibility for Part 2 will be determined based on the patient achieving at least comparable BP control to historical treatment and requiring potassium replacement while on 
baxdrostat that is less than or comparable to historical replacement in patients with a history of hypokalemia. 

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APPENDIX B: CLINICAL LABORATORY ANALYTES
Viral Testing and Serology 
Hepatitis B surface antigen 
Hepatitis C virus RNA
HIV antibody 
 

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APPENDIX C: ELECTROCARDIOGRAM ALERT CRITERIA GUIDANCE
Investigators should contact the Sponsor or designee if any clinically meaningful changes from 
baseline electrocardiograms, including but not limited to those listed below, are noted upon review:
 QTcF 
450 msec (males)
 QTcF 
470 msec (females)
 A > 60 msec increase in QTcF from baseline 
 A  6% increase in QTcF from baseline 
New onset findings included but not limited to: 
 Second degree atrioventricular (AV) block (Mobitz II) 
 Third degree AV block (complete heart block) 
 Acute myocardial infarction 
 New left bundle branch block 
 Severe bradycardia (ventricular rate  40 beats per minute [bpm]) 
 Supraventricular tachycardia (ventricular rate  150 bpm) 
 Torsades de pointes 
 Ventricular tachycardia (  3 beats regardless of rate) 
 Ventricular fibrillation 
 Atrial fibrillation/atrial flutter (ventricular rate  150 bpm) 

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APPENDIX D: EXCLUDED MEDICATIONS
Each concomitant medication should be assessed individually for its potential for a drug-drug 
interaction. For examples of clinical inhibitors and substrates of the listed transporters and clinical 
inducers 
for 
P450 
mediated 
metabolisms, 
see 
the 
online 
reference 
at 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-
table-substrates-inhibitors-and-inducers and at www.CredibleMeds.org (registration required).
An extract of these websites is reflected in Table 3
Table 3 
Examples of Excluded Medications 
Group 
Excluded Medication Examples 
Strong inducers of CYP3Aa
Apalutamide, carbamazepineb, enzalutamidec, mitotane, 
phenytoind, rifampine, St. John’s wortf 
Medications known to prolong QT 
Amiodarone, azithromycin, cilostazol, ciprofloxacin, cisapride, 
citalopram, clarithromycin, dofetilide, domperidone, donepezil, 
erythromycin, escitalopram, fluconazole, hydroxychloroquine, 
levofloxacin, methadone, moxifloxacin, ondansetron, 
pentamidine, quinidine, sotalol, thioridazine, vandetanib 
Sources: Drug Development and Drug Interactions: Table of Substrates, Inhibitors, and Inducers. 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-
inhibitors-and-inducers. Accessed 06 October 2020 
Drugs with known TdP Risk. Available at www.CredibleMeds.org (registration required) Accessed 06 October 
2020. 
Abbreviations: AUC: area under the concentration time curve; CYP: cytochrome P450; DDI: drug-drug interaction. 
a Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or 
drug labeling [03 December 2019]). 
Note: Strong, moderate, and weak inducers are drugs that decrease the AUC of sensitive index substrates of a given 
metabolic pathway by  80%,  50% to  80%, and  20% to  50%, respectively. 
b Strong inducer of CYP2B6 and CYP3A, and weak inducer of CYP2C9. 
c Strong inducer of CYP3A and moderate inducer of CYP2C9 and CYP2C19. 
d Strong inducer of CYP2C19 and CYP3A and moderate inducer of CYP1A2, CYP2B6, CYP2C8, and CYP2C9. 
e Strong inducer of CYP3A and moderate inducer of CYP1A2 and CYP2C19.
f The effect of St John’s wort varies widely and is preparation dependent.  
Beginning at Visit 2, patients will be required to washout mineralocorticoid receptor antagonists 
(such as spironolactone) and remain off through Visit 8 (Follow-Up). During the course of the 
study, antihypertensives including beta blockers, clonidine, methyldopa, minoxidil, nonsteroidal 
anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, 
and/or dihydropyridine calcium channel blockers may be continued to maintain blood pressure.