A Study to Assess the Safety, Tolerability and Efficacy o... | NCT04714320

Label	Type	Description	Intervention Names
Pooled Placebo	Placebo Comparator	Participants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks.	Drug: Placebo
IONIS-AGT-LRx 80 mg	Experimental	Participants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks.	Drug: IONIS-AGT-LRx
IONIS-AGT-LRx 120 mg	Experimental	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.	Drug: IONIS-AGT-LRx

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	ISIS 757456 matching placebo administered by SC injection.	Pooled Placebo

Measure	Description	Time Frame
Change From Baseline in Seated Automated Office SBP to Day 85		Baseline to Day 85

Measure	Description	Time Frame
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit		Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit		Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Males or females aged 18-80 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent
Females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
Males must be abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used
Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)

Exclusion Criteria:

Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced HTN
The use of the following at time of screening and during the course of the study:
- Other medications for the treatment of HTN (e.g., minoxidil, diazoxide, renin inhibitors)
- Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement
- Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
- Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
Unstable/underlying known cardiovascular disease defined as:
- Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV)
- Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening
- Any hemodynamically unstable atrial or ventricular arrhythmias
- Significant uncorrected valvular heart disease
- Any history of stroke or transient ischemic attack < 1 year prior to screening
A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
Participant works nighttime shifts (e.g., 11 PM to 7 AM)

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group		Anniston	Alabama	36207	United States
Central Research Associates, Inc.

ID	Title	Description
FG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, subcutaneous (SC) injection, once weekly for 12 weeks.
FG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 15, 2022

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG00253 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
Race	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Seated Automated Office Systolic Blood Pressure (SBP)- PPS

Mean

Standard Deviation

millimeters of mercury (mmHg)

Title	Denominators	Categories
	ParticipantsBG00045 ParticipantsBG00145 ParticipantsBG002

Seated Automated Office Diastolic Blood Pressure (DBP)- PPS

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00045 ParticipantsBG00145 ParticipantsBG002

Seated Automated Office Systolic Blood Pressure (SBP) -FAS

FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Seated Automated Office Diastolic Blood Pressure (DBP) -FAS

FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00053 ParticipantsBG00154 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Seated Automated Office SBP to Day 85

PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and had no significant protocol deviations that would have been expected to affect efficacy assessment.

Posted

Least Squares Mean

95% Confidence Interval

mmHg

Baseline to Day 85

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts
Participants	OG00045 OG00145 OG00246

Title

Denominators

Categories

Title	Measurements
	OG000-9(-14 to -3) OG001-13(-18 to -8) OG002-9(-14 to -4)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Change From Baseline in Seated Automated Office SBP to Day 85	ANCOVA		=0.135	The stratification factor (screening estimated glomerular filtration rate (eGFR) status [<60 vs. ≥60 mL/min/1.73 m^2]), treatment received, and baseline measure were included in the analysis of covariate (ANCOVA) model as independent variables.													Superiority

Secondary

Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit

PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to Study Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Posted

Mean

Standard Deviation

nmol/L

Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts

Secondary

Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit

Posted

Mean

Standard Deviation

nmol/L

Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts

Secondary

Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit

PPS included all FAS participants who received at least 10 of 12 doses of study drug did not alter antihypertensive medications during treatment period & prior to Day 85 have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates number of participants with data available for analysis at specified time point.

Posted

Mean

Standard Deviation

percent change

Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts

Secondary

Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)

PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to Study Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Overall number of participants analyzed' indicates the number of participants with data available for the analysis of this outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

mmHg

Baseline, Day 85

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Secondary

Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit

PPS analysis set was used. Participants with SBP ≤ 140 mmHg at baseline were excluded from this analysis. 'Overall number of participants analyzed' indicates the number of participants with data available for the analysis of this outcome measure. 'Number analyzed' indicates number of participants with data available for analysis at specified time point.

Posted

Number

percentage of participants

Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts

Secondary

Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit

PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to study day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Posted

Number

percentage of participants

Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once-weekly for 12 weeks.

Secondary

Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit

Posted

Mean

Standard Deviation

mmHg

Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units	Counts

Secondary

Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit

PPS included all FAS participants who received at least 10 of 12 doses of study drug, did not alter antihypertensive medications during treatment period and prior to Day 85,and had no significant protocol deviations that would have been expected to affect efficacy assessment. 'Number analyzed' is the number of participants with data available for analysis at the specified timepoint

Posted

Least Squares Mean

95% Confidence Interval

mmHg

Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169

ID	Title	Description
OG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
OG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
OG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Units

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 8	Regression, Logistic	=0.280	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 8	Regression, Logistic	=0.648	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 15	Regression, Logistic	=0.416	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 15	Regression, Logistic	=0.900	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 22	Regression, Logistic	=0.627	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 22	Regression, Logistic	=0.921	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 29	Regression, Logistic	=0.464	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 29	Regression, Logistic	=0.458	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 36	Regression, Logistic	=0.779	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 36	Regression, Logistic	=0.629	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 43	Regression, Logistic	=0.242	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 43	Regression, Logistic	=0.290	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 50	Regression, Logistic	=0.349	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 50	Regression, Logistic	=0.532	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 57	Regression, Logistic	=0.205	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 57	Regression, Logistic	=0.368	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 64	Regression, Logistic	=0.084	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 64	Regression, Logistic	=0.179	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 71	Regression, Logistic	=0.584	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 71	Regression, Logistic	=0.762	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 78	Regression, Logistic	=0.675	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 78	Regression, Logistic	=0.166	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 85	Regression, Logistic	=0.090	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 85	Regression, Logistic	=0.488	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 92	Regression, Logistic	=0.218	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 92	Regression, Logistic	=0.232	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 106	Regression, Logistic	=0.421	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 106	Regression, Logistic	=0.815	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 120	Regression, Logistic	=0.711	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 120	Regression, Logistic	=0.514	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 148	Regression, Logistic	=0.479	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 148	Regression, Logistic	=0.292	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg at Day 169	Regression, Logistic	=0.528	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg at Day 169	Regression, Logistic	=0.946	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 8	Regression, Logistic	=0.552	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 8	Regression, Logistic	=0.598	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 15	Regression, Logistic	=0.184	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 15	Regression, Logistic	=0.614	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 22	Regression, Logistic	=0.933	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 22	Regression, Logistic	=0.803	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 29	Regression, Logistic	=0.686	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 29	Regression, Logistic	=0.752	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 36	Regression, Logistic	=0.106	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 36	Regression, Logistic	=0.779	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 43	Regression, Logistic	=0.323	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 43	Regression, Logistic	=0.991	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 50	Regression, Logistic	=0.973	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 50	Regression, Logistic	=0.230	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 57	Regression, Logistic	=0.792	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 57	Regression, Logistic	=0.744	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 64	Regression, Logistic	=0.925		Superiority	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 64	Regression, Logistic	=0.991	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 71	Regression, Logistic	=0.530		Superiority	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 71	Regression, Logistic	=0.849	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 78	Regression, Logistic	=0.953	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 78	Regression, Logistic	=0.884	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 85	Regression, Logistic	=0.230	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 85	Regression, Logistic	=0.589	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 92	Regression, Logistic	=0.919	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 92	Regression, Logistic	=0.753	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 106	Regression, Logistic	=0.747	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 106	Regression, Logistic	=0.764	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 120	Regression, Logistic	=0.527	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 120	Regression, Logistic	=0.639	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 148	Regression, Logistic	=0.744	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 148	Regression, Logistic	=0.539	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office DBP ≤ 80 mmHg at Day 169	Regression, Logistic	=0.417	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office DBP ≤ 80 mmHg at Day 169	Regression, Logistic	=0.466	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 8	Regression, Logistic	=0.380	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 8	Regression, Logistic	=0.730	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 15	Regression, Logistic	=0.595	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 15	Regression, Logistic	=0.279	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 22	Regression, Logistic	=0.196	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 22	Regression, Logistic	=0.728	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 29	Regression, Logistic	=0.453	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 29	Regression, Logistic	=0.681	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 36	Regression, Logistic	=0.863	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 36	Regression, Logistic	=0.837	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 43	Regression, Logistic	=0.504	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 43	Regression, Logistic	=0.531	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 50	Regression, Logistic	=0.600	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 50	Regression, Logistic	=0.830	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 57	Regression, Logistic	=0.209	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 57	Regression, Logistic	=0.809	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 64	Regression, Logistic	=0.045	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 64	Regression, Logistic	=0.104	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 71	Regression, Logistic	=0.690	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 71	Regression, Logistic	=0.590	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 78	Regression, Logistic	=0.538	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 78	Regression, Logistic	=0.407	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 85	Regression, Logistic	=0.398	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 85	Regression, Logistic	=0.930	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 92	Regression, Logistic	=0.111	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 92	Regression, Logistic	=0.196	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 106	Regression, Logistic	=0.816	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 106	Regression, Logistic	=0.473	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 120	Regression, Logistic	=0.615	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 120	Regression, Logistic	=0.214	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 148	Regression, Logistic	=0.575	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 148	Regression, Logistic	=0.276	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG001	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 169	Regression, Logistic	=0.573	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority
OG000 OG002	Seated Automated Office SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 169	Regression, Logistic	=0.706	Stratification factor (screening eGFR status (<60 vs ≤ 60 mL/min/1.73 m2)), treatment received and baseline measure were included in Logistic Regression model, firth correction was applied if quasi-complete separation of data points was detected.	Superiority

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0011 affected54 at risk EG0020 affected53 at risk
Cardiac arrest	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0010 affected54 at risk EG0021 affected53 at risk
Cerebral infarction	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0011 affected54 at risk EG0020 affected53 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected53 at risk EG0010 affected54 at risk EG0020 affected53 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0010 affected54 at risk EG0021 affected53 at risk
Aortic dissection	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0010 affected54 at risk EG0021 affected53 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0013 affected54 at risk EG0021 affected53 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0013 affected54 at risk EG0022 affected53 at risk
Injection site erythema	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0012 affected54 at risk EG0023 affected53 at risk
COVID-19	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected53 at risk EG0012 affected54 at risk EG0023 affected53 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 affected53 at risk EG0015 affected54 at risk EG0023 affected53 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0013 affected54 at risk EG0021 affected53 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0014 affected54 at risk EG0020 affected53 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected53 at risk EG0013 affected54 at risk EG0021 affected53 at risk
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0004 affected53 at risk EG0011 affected54 at risk EG0022 affected53 at risk
Hypertension	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0003 affected53 at risk EG0010 affected54 at risk EG0022 affected53 at risk

ID	Term
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
BG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
BG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pooled Placebo	Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.	0	53	1	53	9	53
EG001	IONIS-AGT-LRx 80 mg	Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.	0	54	2	54	18	54
EG002	IONIS-AGT-LRx 120 mg	Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.	1	53	1	53	14	53