Zilebesiran as Add-on Therapy in Patients With Hypertensi... | NCT05103332 | Trialant
NCT05103332
Sponsor
Alnylam Pharmaceuticals
Status
Completed
Last Update Posted
Nov 3, 2025Actual
Enrollment
663Actual
Phase
Phase 2
Conditions
Hypertension
Interventions
Indapamide
Amlodipine
Olmesartan
Placebo
Zilebesiran
Countries
United States
Canada
Estonia
Germany
Latvia
Lithuania
Poland
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT05103332
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ALN-AGT01-003
Secondary IDs
ID
Type
Description
Link
2021-003776-13
EudraCT Number
Brief Title
Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
Official Title
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication
Acronym
KARDIA-2
Organization
Alnylam PharmaceuticalsINDUSTRY
Status Module
Record Verification Date
Oct 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 5, 2021Actual
Primary Completion Date
Dec 11, 2023Actual
Completion Date
Sep 13, 2024Actual
First Submitted Date
Oct 22, 2021
First Submission Date that Met QC Criteria
Oct 22, 2021
First Posted Date
Nov 2, 2021Actual
Results Waived
Not provided
Results First Submitted Date
May 9, 2025
Results First Submitted that Met QC Criteria
Jun 19, 2025
Results First Posted Date
Jul 9, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Sep 12, 2024
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Jul 9, 2025Actual
Last Update Submitted Date
Oct 17, 2025
Last Update Posted Date
Nov 3, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Alnylam PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to evaluate the effect of zilebesiran on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of zilebesiran as add-on therapy.
Detailed Description
Not provided
Conditions Module
Conditions
Hypertension
Keywords
High blood pressure
Hypertension
Hypertensive
siRNA
Angiotensinogen
AGT
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
663Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo (Add-on to Indapamide)
Placebo Comparator
Following a 4-week run-in treatment on indapamide, 2.5 milligrams (mg), orally, once daily (QD), eligible participants were randomized to receive placebo matched to zilebesiran as a subcutaneous (SC) injection on Day 1 of 6-month double-blind (DB) treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran once every 6 months (Q6M) during the open-label extension (OLE) period. Upon implementation of Amendment 3, the OLE period was closed.
Drug: Indapamide
Drug: Placebo
Drug: Zilebesiran
Zilebesiran (Add-on to Indapamide)
Experimental
Following a 4-week run-in treatment on indapamide, 2.5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Drug: Indapamide
Drug: Zilebesiran
Placebo (Add-on to Amlodipine)
Placebo Comparator
Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Indapamide
Drug
Indapamide administered orally
Placebo (Add-on to Indapamide)
Zilebesiran (Add-on to Indapamide)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Secondary Outcomes
Measure
Description
Time Frame
Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Office SBP at Screening as follows:
≥155 mmHg and ≤180 mmHg for patients with untreated hypertension
≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications
24-hour mean SBP ≥130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in
Exclusion Criteria:
Secondary hypertension, orthostatic hypotension
Elevated potassium <lower limit of normal (LLN) range or >5 milliequivalents per liter (mEq/L)
Estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m^2
Received an investigational agent within the last 30 days
Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, or laboratory evidence of diabetes during screening without known diagnosis of diabetes
History of any cardiovascular event within 6 months prior to randomization
Desai AS, Karns AD, Badariene J, Aswad A, Neutel JM, Kazi F, Park W, Stiglitz D, Makarova N, Havasi A, Zappe DH, Saxena M; KARDIA-2 Study Group. Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial. JAMA. 2025 Jul 1;334(1):46-55. doi: 10.1001/jama.2025.6681.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the United States (US) and/or the European Union (EU).
Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Before Protocol Amendment 3 (PA3), participants completing DB period could join a separate zilebesiran OLE study. Those completing DB before OLE study availability entered OLE period in this study to receive zilebesiran until transition. Others ineligible for OLE study/discontinued drug in DB could enter safety follow-up(SFU). With PA3, OLE period was closed & plans for OLE study canceled. Ongoing DB participants entered SFU at completion; those in OLE stopped treatment & transitioned to SFU.
Recruitment Details
A total of 78 clinical sites in North America (66=United States [US] & 12=Canada) & 24 clinical sites in Europe (10=United Kingdom [UK]) enrolled participants in this study. 663 participants who met eligibility criteria after run-in with protocol-assigned background medication (indapamide, amlodipine, olmesartan) were randomized to zilebesiran or placebo in double-blind (DB) period, with the option to receive zilebesiran in open-label extension period (OLE). 1 month=28 days for this study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Drug: Amlodipine
Drug: Zilebesiran
Placebo (Add-on to Olmesartan)
Placebo Comparator
Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 milliliters per minute [mL/min] at screening enrolled at sites outside of the United States [US] consistent with local labeling), eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Drug: Olmesartan
Drug: Placebo
Drug: Zilebesiran
Zilebesiran (Add-on to Olmesartan)
Experimental
Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 mL/min at screening enrolled at sites outside of the US consistent with local labeling), eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Drug: Olmesartan
Drug: Zilebesiran
Amlodipine
Drug
Amlodipine administered orally
Placebo (Add-on to Amlodipine)
Zilebesiran (Add-on to Amlodipine)
Olmesartan
Drug
Olmesartan administered orally
Placebo (Add-on to Olmesartan)
Zilebesiran (Add-on to Olmesartan)
Placebo
Drug
Placebo administered by SC injection
Placebo (Add-on to Amlodipine)
Placebo (Add-on to Indapamide)
Placebo (Add-on to Olmesartan)
Zilebesiran
Drug
Zilebesiran administered by SC injection
Placebo (Add-on to Amlodipine)
Placebo (Add-on to Indapamide)
Placebo (Add-on to Olmesartan)
Zilebesiran (Add-on to Amlodipine)
Zilebesiran (Add-on to Indapamide)
Zilebesiran (Add-on to Olmesartan)
ALN-AGT01
Baseline and Month 3
Baseline and Month 3
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the area under the curve (AUC) of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
Baseline through Month 6
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
Baseline through Month 6
Indapamide: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
Month 6
Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
Baseline and Month 3
Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline through Month 3
Indapamide: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline through Month 3
Indapamide: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
Baseline and Month 6
Indapamide: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
Baseline and Month 6
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
Baseline through Month 6
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
Baseline through Month 6
Indapamide: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
Baseline, and Month 2, 3 and 6
Indapamide: Percent Change From Baseline in Serum Angiotensinogen (AGT)
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
Amlodipine: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
Baseline through Month 6
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
Baseline through Month 6
Amlodipine: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
Month 6
Amlodipine: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Amlodipine: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
Baseline and Month 3
Amlodipine: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline through Month 3
Amlodipine: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline through Month 3
Amlodipine: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
Baseline and Month 6
Amlodipine: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
Baseline and Month 6
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
Baseline through Month 6
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
Baseline through Month 6
Amlodipine: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
Baseline, and Month 2, 3 and 6
Amlodipine: Percent Change From Baseline in Serum AGT
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
Olmesartan: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
Baseline through Month 6
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
Baseline through Month 6
Olmesartan: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
Month 6
Olmesartan: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline and Month 3
Olmesartan: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
Baseline and Month 3
Olmesartan: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
Baseline through Month 3
Olmesartan: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
Baseline through Month 3
Olmesartan: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
Baseline and Month 6
Olmesartan: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
Baseline and Month 6
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
Baseline through Month 6
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
Baseline through Month 6
Olmesartan: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
Baseline, and Month 2, 3 and 6
Olmesartan: Percent Change From Baseline in Serum AGT
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
Tempe
Arizona
85281
United States
Clinical Trial Site
Tempe
Arizona
85282
United States
Clinical Trial Site
Bell Gardens
California
90201
United States
Clinical Trials Site
Beverly Hills
California
90211
United States
Clinical Trial Site
Canoga Park
California
91304
United States
Clinical Trial Site
Carlsbad
California
92008
United States
Clinical Trial Site
Encinitas
California
92024
United States
Clinical Trial Site
Garden Grove
California
92844
United States
Clinical Trial Site
Hollywood
California
91606
United States
Clinical Trial Site
Huntington Beach
California
92647
United States
Clinical Trial Site
Irvine
California
92614
United States
Clinical Trial Site
Long Beach
California
90805
United States
Clinical Trial Site
Los Angeles
California
90057
United States
Clinical Trial Site
Mission Hills
California
91345
United States
Clinical Trial Site
Oceanside
California
92056
United States
Clinical Trial Site
Panorama City
California
91402
United States
Clinical Trial Site
San Diego
California
92103
United States
Clinical Trial Site
Santa Clarita
California
91355
United States
Clinical Trial Site
South Gate
California
90280
United States
Clinical Trial Site
Tustin
California
92780
United States
Clinical Trial Site
Upland
California
91786
United States
Clinical Trial Site
Washington D.C.
District of Columbia
20011
United States
Clinical Trial Site
Clearwater
Florida
33756
United States
Clinical Trial Site
Coconut Creek
Florida
33073
United States
Clinical Trial Site
Coral Gables
Florida
33134
United States
Clinical Trial Site
Hollywood
Florida
33021
United States
Clinical Trial Site
Hollywood
Florida
33024
United States
Clinical Trial Site
Inverness
Florida
34452
United States
Clinical Trial Site
Jacksonville
Florida
32256
United States
Clinical Trial Site
Miami
Florida
33032
United States
Clinical Trial Site
Miami
Florida
33125
United States
Clinical Trial Site
Miami
Florida
33135
United States
Clinical Trial Site
Miami
Florida
33144
United States
Clinical Trial Site
Miami
Florida
33176
United States
Clinical Trial Site
Naples
Florida
34105
United States
Clinical Trial Site
Orlando
Florida
32162
United States
Clinical Trial Site
Orlando
Florida
32801
United States
Clinical Trial Site
Pembroke Pines
Florida
33027
United States
Clinical Trial Site
Tampa
Florida
33603
United States
Clinical Trial Site
Winter Haven
Florida
33880
United States
Clinical Trial Site
Winter Park
Florida
32789
United States
Clinical Trial Site
Acworth
Georgia
30101
United States
Clinical Trial Site
Canton
Georgia
30114
United States
Clinical Trial Site
Columbus
Georgia
31904
United States
Clinical Trial Site
Savannah
Georgia
31406
United States
Clinical Trial Site
Louisville
Kentucky
40202
United States
Clinical Trial Site
New Orleans
Louisiana
70769
United States
Clinical Trial Site
Southgate
Michigan
48195
United States
Clinical Trial Site
Jackson
Mississippi
39209
United States
Clinical Trial Site
Hazelwood
Missouri
63042
United States
Clinical Trial Site
Jefferson City
Missouri
65109
United States
Clinical Trial Site
New York
New York
10036
United States
Clinical Trial Site
Greensboro
North Carolina
27403
United States
Clinical Trial Site
Greensboro
North Carolina
27410
United States
Clinical Trial Site
Monroe
North Carolina
28112
United States
Clinical Trial site
Winston-Salem
North Carolina
27157
United States
Clinical Trial Site
Norman
Oklahoma
73072
United States
Clinical Trial Site
Little River
South Carolina
29566
United States
Clinical Trial Site
Memphis
Tennessee
38119
United States
Clinical Trial Site
Amarillo
Texas
79109
United States
Clinical Trial Site
Coppell
Texas
75019
United States
Clinical Trial Site
Dallas
Texas
75251
United States
Clinical Trial Site
Houston
Texas
77074
United States
Clinical Trial Site
Houston
Texas
77081
United States
Clinical Trial Site
Lake Jackson
Texas
77566
United States
Clinical Trial Site
Plano
Texas
75024
United States
Clinical Trial Site
Sherman
Texas
75092
United States
Clinical Trial Site
Splendora
Texas
77372
United States
Clinical Trial Site
Stephenville
Texas
76401
United States
Clinical Trial Site
Tomball
Texas
77375
United States
Clinical Trial Site
Waco
Texas
76708
United States
Clinical Trial Site
Burke
Virginia
22015
United States
Clinical Trial Site
Kenosha
Wisconsin
53142
United States
Clinical Trial Site
Brampton
Ontario
Canada
Clinical Trial Site
Concord
Ontario
Canada
Clinical Trial Site
London
Ontario
N5W 6A2
Canada
Clinical Trial Site
Toronto
Ontario
Canada
Clinical Trial Site
Winnipeg
Ontario
Canada
Clinical Trial Site
Chicoutimi
Quebec
Canada
Clinical Trial Site
Lévis
Quebec
Canada
Clinical Trial Site
Pointe-Claire
Quebec
Canada
Clinical Trial Site
Québec
Quebec
Canada
Clinical Trial Site
Sherbrooke
Quebec
Canada
Clinical Trial Site
Trois-Rivières
Quebec
Canada
Clinical Trial Site
Québec
Canada
Clinical Trial Site
Tartu
Estonia
Clinical Trial Site
Frankfurt
Germany
Clinical Trial Site
Riga
Latvia
Clinical Trial Site
Kaunas
Lithuania
Clinical Trial Site
Vilnius
Lithuania
Clinical Trial Site
Częstochowa
Poland
Clinical Trial Site
Gdansk
Poland
Clinical Trial Site
Katowice
Poland
Clinical Trial Site
Staszów
Poland
Clinical Trial Site
Warsaw
Poland
Clinical Trial Site
Wroclaw
Poland
Clinical Trial Site
Bellshill
Lanarkshire
ML4 3NJ
United Kingdom
Clinical Trial Site
Carshalton
United Kingdom
Clinical Trial Site
Edinburgh
United Kingdom
Clinical Trial Site
Fowey
United Kingdom
Clinical Trial Site
Glasgow
United Kingdom
Clinical Trial Site
Lancashire Preston
United Kingdom
Clinical Trial Site
Liskeard
United Kingdom
Clinical Trial Site
London
United Kingdom
Clinical Trial Site
Manchester
United Kingdom
Clinical Trial Site
Newquay
United Kingdom
Clinical Trial Site
Plymouth
United Kingdom
Clinical Trial Site
Sheffield
United Kingdom
Clinical Trial Site
Torpoint
United Kingdom
FG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
FG002
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
FG003
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
FG004
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
FG005
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
FG006
DB Period (Placebo) to OLE Period (Zilebesiran) [Indapamide Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with indapamide was discontinued at the start of OLE period.
FG007
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Indapamide Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with indapamide was discontinued at the start of OLE period.
FG008
DB Period (Placebo) to OLE Period (Zilebesiran) [Amlodipine Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with amlodipine was discontinued at the start of OLE period.
FG009
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Amlodipine Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with amlodipine was discontinued at the start of OLE period.
FG010
DB Period (Placebo) to OLE Period (Zilebesiran) [Olmesartan Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with olmesartan was discontinued at the start of OLE period.
FG011
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Olmesartan Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with olmesartan was discontinued at the start of OLE period.
FG012
DB (Placebo) to SFU or OLE (Zilebesiran) to SFU [Indapamide Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (placebo) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG013
DB (Zilebesiran) to SFU or OLE (Zilebesiran) to SFU [Indapamide Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (zilebesiran) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG014
DB (Placebo) to SFU or OLE (Zilebesiran) to SFU [Amlodipine Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (placebo) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG015
DB (Zilebesiran) to SFU or OLE (Zilebesiran) to SFU [Amlodipine Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (zilebesiran) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG016
DB (Placebo) to SFU or OLE (Zilebesiran) to SFU [Olmesartan Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (placebo) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG017
DB (Zilebesiran) to SFU or OLE (Zilebesiran) to SFU [Olmesartan Cohort]
Prior to Amendment 3, participants who did not enter OLE period or who discontinued treatment (zilebesiran) during DB period entered SFU period.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly, and those already in OLE period did not receive any additional study drug in OLE and transitioned to the SFU period.
FG00065 subjects
FG00165 subjects
FG002120 subjects
FG003120 subjects
FG004146 subjects
FG005147 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
Modified Full Analysis Set (mFAS)
mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm.
FG00064 subjects
FG00163 subjects
FG002120 subjects
FG003118 subjects
FG004146 subjects
FG005147 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
Modified Safety Analysis Set (mSAS)
mSAS included all participants who received any amount of the study drug. Participants were grouped according to the treatment actually received. 1 participant randomized to Placebo (Olmesartan) received zilebesiran, hence, was considered in the Zilebesiran (Olmesartan) arm for safety analysis.
FG00064 subjects
FG00163 subjects
FG002120 subjects
FG003118 subjects
FG004145 subjects
FG005148 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG00063 subjects
FG00159 subjects
FG002114 subjects
FG003115 subjects
FG004143 subjects
FG005139 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
NOT COMPLETED
FG0002 subjects
FG0016 subjects
FG0026 subjects
FG0035 subjects
FG0043 subjects
FG0058 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0052 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
Physician Decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Participant Stopped Participation in the Study
FG0002 subjects
FG0013 subjects
FG0025 subjects
FG0033 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
OLE Period (24 Months=672 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG00626 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG00730 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG00848 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG00944 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG01066 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG01160 subjectsParticipants who completed the 6-month DB period and met the eligibility criteria as per the study plan before implementation of protocol amendment 3 entered the OLE period.
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
SFU Period (6 Months=168 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG01263 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
FG01359 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
FG014114 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
FG015115 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
FG016143 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
FG017139 subjectsUpon implementation of Amendment 3, all participants who had completed the DB period entered the SFU period, and those in the OLE period did not receive any additional study drug in OLE and entered the SFU period.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG002
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG003
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG004
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG005
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00064
BG00163
BG002120
BG003118
BG004146
BG005147
BG006658
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
Title
Measurements
BG00060.6± 10.2
BG00157.9± 10.7
BG00258.4± 9.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00025
BG00130
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00028
BG00127
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian
BG0000
BG0014
BG002
24-hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM)
SBP assessed by ABPM at baseline is reported here. 24-hour ABPM device was programmed to take readings every 20 minutes during day(6 am-9:59 pm) & every 30 minutes during night(10 pm-5:59 am). ABPM was considered adequate if: number of successful daytime readings were ≥33; number of successful nighttime readings were≥11; no more than 3 hours are not represented(3 sections of 60 minutes with 0 valid readings). To summarize 24-hour ABPM, hourly adjusted mean was calculated. Hourly adjusted mean was average blood pressure(BP) for each hour of the day. 24-hour mean was average of the hourly means.
Mean
Standard Deviation
millimeter of mercury (mmHg)
Title
Denominators
Categories
Title
Measurements
BG000143.2± 8.4
BG001
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
Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00056
OG00153
Title
Denominators
Categories
Title
Measurements
OG000-3.7± 1.56
OG001-15.7± 1.60
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort & handle primary & key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for SBP, assessed using ABPM, while participants were on & within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
<0.0001
MMRM: Fixed factors: treatment, visit, treatment-by-visit interaction, race (black/all other races); Covariates: Baseline (BA) 24-hour mean SBP using ABPM & BA estimated glomerular filtration rate (eGFR). Unstructured covariance matrix was used.
Difference in LS Mean
-12.1
Standard Error of the Mean
2.24
2-Sided
95
-16.5
-7.6
Primary
Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Primary
Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm.
Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocolspecified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Secondary
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the area under the curve (AUC) of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Number
percentage of participants
Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Secondary
Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Secondary
Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline, and Month 2, 3 and 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Indapamide)
Participants were randomized to receive placebo matched to zilebesiran, as a subcutaneous (SC) injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Indapamide: Percent Change From Baseline in Serum Angiotensinogen (AGT)
Modified Pharmacodynamic (PD) Analysis Set included all participants who received at least 1 full dose of study drug. All by-treatment analyses based on the Modified PD Analysis Set were grouped according to the treatment actually received. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Mean
Standard Deviation
percent change
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
ID
Title
Description
OG000
Placebo (Add-on to Indapamide)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Zilebesiran (Add-on to Indapamide)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Deviation
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Number
percentage of participants
Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Secondary
Amlodipine: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline, and Month 2, 3 and 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Amlodipine)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Amlodipine: Percent Change From Baseline in Serum AGT
Modified PD Analysis Set included all participants who received at least 1 full dose of study drug. All by-treatment analyses based on the Modified PD Analysis Set were grouped according to the treatment actually received. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Mean
Standard Deviation
percent change
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
ID
Title
Description
OG000
Placebo (Add-on to Amlodipine)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Zilebesiran (Add-on to Amlodipine)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Change From Baseline at Month 3 in Office SBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Number
percentage of participants
Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Secondary
Olmesartan: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Change From Baseline at Month 3 in Office DBP - Censored Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP and DBP, while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 3
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data
24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP and DBP assessed by ABPM are included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP and DBP, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline and Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for DBP assessed by ABPM were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data
Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office DBP were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline through Month 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data
ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for daytime and nighttime SBP and DBP, assessed by ABPM, were included in the analysis for this endpoint.
The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Least Squares Mean
Standard Error
mmHg
Baseline, and Month 2, 3 and 6
ID
Title
Description
OG000
DB Period: Placebo (Add-on to Olmesartan)
Participants were randomized to receive placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Secondary
Olmesartan: Percent Change From Baseline in Serum AGT
Modified PD Analysis Set included all participants who received at least 1 full dose of study drug. All by-treatment analyses based on the Modified PD Analysis Set were grouped according to the treatment actually received. Number analyzed are unique number of participants out of all the assessed participants who were evaluable for the specified category. Different participants may have contributed data for each category.
Posted
Mean
Standard Deviation
percent change
Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
ID
Title
Description
OG000
Placebo (Add-on to Olmesartan)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
OG001
Zilebesiran (Add-on to Olmesartan)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Time Frame
Run-in: 4 weeks; DB Period (DBP): Day1 to Month6 (168 days); Zilebesiran (zil) Treatment Period: First zil dose to 6 months after last dose [Placebo (pbo)/Zil: Months 6 to 30 (672 days); Zil/Zil: Day1 to Month30 (840 days)]; SFU: 6 months (168 days); 1 month=28 days. Run-in: Participants eligible after run-in who received at least 1 dose of study drug in DBP, grouped per their background medication. DBP: mSAS; SFU: Participants from mSAS, grouped per last treatment in DB/OLE before SFU entry.
Description
As pre-specified in SAP, after DBP, AEs were reported by treatment sequence (Zil/Zil or pbo/Zil) for zilebesiran treatment period using All Zilebesiran Treated Set (Arms 10-15). Zil/Zil arm received zilebesiran in both DB & OLE. Hence, AEs' data for DB+OLE have been reported together. This set gives AEs for all participants receiving zilebesiran, including participants on zilebesiran during DB & continuing it after Month 6 & those on placebo in DB later & switching to zilebesiran after Month 6.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Run-in: Indapamide
Participants who cleared screening received open-label therapy with indapamide 2.5 mg orally once daily (QD) as their protocol-specified background antihypertensive medication during a Run-in period of at least 4 weeks.
0
127
0
127
0
127
EG001
Run-in: Amlodipine
Participants who cleared screening received open-label therapy with amlodipine 5 mg orally QD as their protocol-specified background antihypertensive medication during a Run-in period of at least 4 weeks.
0
238
0
238
0
238
EG002
Run-in: Olmesartan
Participants who cleared screening received open-label therapy with olmesartan 40 mg orally QD [or 20 mg orally QD for participants with creatinine clearance ≤ 60 mL/min at screening enrolled at sites outside of the US] as their protocol-specified background antihypertensive medication during a Run-in period of at least 4 weeks.
0
293
1
293
0
293
EG003
DB Period: Placebo (Add-on to Indapamide)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
64
2
64
11
64
EG004
DB Period: Zilebesiran (Add-on to Indapamide)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
63
0
63
14
63
EG005
DB Period: Placebo (Add-on to Amlodipine)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
120
1
120
21
120
EG006
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
118
3
118
26
118
EG007
DB Period: Placebo (Add-on to Olmesartan)
Participants received placebo matched to zilebesiran, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
145
4
145
29
145
EG008
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants received zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
0
148
4
148
41
148
EG009
DB Period (Placebo) to OLE Period (Zilebesiran) [Indapamide Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with indapamide was discontinued at the start of OLE period.
0
26
1
26
1
26
EG010
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Indapamide Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with indapamide was discontinued at the start of OLE period.
0
63
1
63
19
63
EG011
DB Period (Placebo) to OLE Period (Zilebesiran) [Amlodipine Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with amlodipine was discontinued at the start of OLE period.
0
48
1
48
6
48
EG012
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Amlodipine Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with amlodipine was discontinued at the start of OLE period.
0
118
3
118
36
118
EG013
DB Period (Placebo) to OLE Period (Zilebesiran) [Olmesartan Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and received treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with olmesartan was discontinued at the start of OLE period.
0
66
3
66
23
66
EG014
DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Olmesartan Cohort]
Prior to Amendment 3, participants who completed the DB period before a separate OLE study was available, entered the OLE period of this study and continued treatment with zilebesiran 600 mg SC q6M. Protocol-specified background antihypertensive treatment with olmesartan was discontinued at the start of OLE period.
0
148
7
148
51
148
EG015
DB (Placebo) to SFU [Indapamide Cohort]
Participants treated with placebo during DB period who did not enter the OLE period (prior to Amendment 3) or who discontinued treatment during the DB period entered the SFU period for safety monitoring.
No treatment was administered in SFU.
0
38
0
38
0
38
EG016
DB (Zilebesiran) to SFU or OLE to SFU [Indapamide Cohort]
Prior to Amendment 3, participants treated with zilebesiran who did not enter the OLE Period or who discontinued treatment (zilebesiran) during the DB period entered the SFU period for safety monitoring.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly. Participants who were already in OLE period (after completing treatment with zilebesiran/placebo in DB period) did not receive any additional study drug in OLE and transitioned to the SFU period for safety monitoring.
No treatment was administered in SFU.
0
89
1
89
0
89
EG017
DB (Placebo) to SFU [Amlodipine Cohort]
Participants treated with placebo during DB period who did not enter the OLE period (prior to Amendment 3) or who discontinued treatment during the DB period entered the SFU period for safety monitoring.
No treatment was administered in SFU.
1
72
0
72
0
72
EG018
DB (Zilebesiran) to SFU or OLE to SFU [Amlodipine Cohort]
Prior to Amendment 3, participants treated with zilebesiran who did not enter the OLE Period or who discontinued treatment (zilebesiran) during the DB period entered the SFU period for safety monitoring.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly. Participants who were already in OLE period (after completing treatment with zilebesiran/placebo in DB period) did not receive any additional study drug in OLE and transitioned to the SFU period for safety monitoring.
No treatment was administered in SFU.
0
166
0
166
0
166
EG019
DB (Placebo) to SFU [Olmesartan Cohort]
Participants treated with placebo during DB period who did not enter the OLE period (prior to Amendment 3) or who discontinued treatment during the DB period entered the SFU period for safety monitoring.
No treatment was administered in SFU.
0
79
0
79
0
79
EG020
DB (Zilebesiran) to SFU or OLE to SFU [Olmesartan Cohort]
Prior to Amendment 3, participants treated with zilebesiran who did not enter the OLE Period or who discontinued treatment (zilebesiran) during the DB period entered the SFU period for safety monitoring.
Upon implementation of Amendment 3, participants who completed the DB period entered the SFU period directly. Participants who were already in OLE period (after completing treatment with zilebesiran/placebo in DB period) did not receive any additional study drug in OLE and transitioned to the SFU period for safety monitoring.
No treatment was administered in SFU.
1
214
1
214
0
214
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute myocardial infarction
Cardiac disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG0030 affected64 at risk
EG0040 affected63 at risk
EG0050 affected120 at risk
EG0060 affected118 at risk
EG0070 affected145 at risk
EG0081 affected148 at risk
EG0090 affected26 at risk
EG0100 affected63 at risk
EG0110 affected48 at risk
EG0120 affected118 at risk
EG0130 affected66 at risk
EG0141 affected148 at risk
EG0150 affected38 at risk
EG0160 affected89 at risk
EG0170 affected72 at risk
EG0180 affected166 at risk
EG0190 affected79 at risk
EG0200 affected214 at risk
Atrial fibrillation
Cardiac disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Cardiac failure chronic
Cardiac disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Impaired gastric emptying
Gastrointestinal disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Incarcerated umbilical hernia
Gastrointestinal disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Proctitis
Gastrointestinal disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Chills
General disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Oedema peripheral
General disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Appendicitis
Infections and infestations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Cellulitis
Infections and infestations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Helicobacter gastritis
Infections and infestations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Tracheobronchitis
Infections and infestations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0021 affected293 at risk
EG003
Concussion
Injury, poisoning and procedural complications
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Pelvic fracture
Injury, poisoning and procedural complications
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Osteonecrosis
Musculoskeletal and connective tissue disorders
MedDRA26.0
Systematic Assessment
EG0000 affected127 at risk
EG0010 affected238 at risk
EG0020 affected293 at risk
EG003
Renal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LS Mean Difference between zilebesiran (add on to indapamide) and placebo (add on to indapamide), 95% CI was calculated using MMRM model.
Superiority
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000100
OG00199
Title
Denominators
Categories
Title
Measurements
OG000-0.7± 1.14
OG001-10.5± 1.15
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort & handle primary & key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for SBP, assessed using ABPM, while participants were on & within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline 24-hour mean SBP assessed by ABPM and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-9.7
Standard Error of the Mean
1.61
2-Sided
95
-12.9
-6.6
LS Mean Difference between zilebesiran (add on to amlodipine) and placebo (add on to amlodipine), 95% CI was calculated using MMRM model.
Superiority
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000114
OG001115
Title
Denominators
Categories
Title
Measurements
OG000-3.2± 1.34
OG001-7.7± 1.33
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort & handle primary & key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for SBP, assessed using ABPM, while subjects were on & within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
=0.0183
MMRM: Fixed factors: treatment, visit, treatment-by-visit interaction, race (black/all other races); Covariates: Baseline (BA) 24-hour mean SBP using ABPM & BA eGFR. Unstructured covariance matrix was used.
Difference in LS Mean
-4.5
Standard Error of the Mean
1.89
2-Sided
95
-8.2
-0.8
LS Mean Difference between zilebesiran (add on to olmesartan) and placebo (add on to olmesartan), 95% CI was calculated using MMRM model.
Superiority
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00055
OG00158
Title
Denominators
Categories
Title
Measurements
OG000-0.8± 1.55
OG001-19.3± 1.52
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-18.5
Standard Error of the Mean
2.17
2-Sided
95
-22.8
-14.2
LS Mean Difference between zilebesiran (add on to indapamide) and placebo (add on to indapamide), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG00057
OG00153
Title
Denominators
Categories
Title
Measurements
OG000-4.6± 1.30
OG001-15.6± 1.35
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline 24-hour mean SBP assessed by ABPM and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-11
Standard Error of the Mean
1.88
2-Sided
95
-14.7
-7.3
LS Mean Difference between zilebesiran (add on to indapamide) and placebo (add on to indapamide), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG00060
OG00158
Title
Denominators
Categories
Title
Measurements
OG000-4.5± 1.16
OG001-18.1± 1.18
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for office SBP were included in the analysis for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-13.6
Standard Error of the Mean
1.66
2-Sided
95
-16.9
-10.3
LS Mean Difference between zilebesiran (add on to indapamide) and placebo (add on to indapamide), 95% CI was calculated using MMRM model.
Superiority
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00057
OG00153
Title
Denominators
Categories
Title
Measurements
OG00014.0
OG00164.2
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05.
Regression, Logistic
<0.0001
Logistic regression model included treatment and race (black or all other races) as factors and baseline 24-hour mean SBP and baseline eGFR as covariates.
Odds Ratio (OR)
12.39
2-Sided
95
4.61
33.29
Superiority
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00056
OG00153
Title
Denominators
Categories
Title
Measurements
OG000-1.3± 0.87
OG001-9.1± 0.89
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00055
OG00158
Title
Denominators
Categories
Title
Measurements
OG000-0.2± 1.03
OG001-10.5± 1.01
Units
Counts
Participants
OG00056
OG00153
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-2.5± 1.22
OG001-15.4± 1.26
24-hour Mean DBP
Title
Measurements
OG000-0.9± 0.76
OG001-8.7± 0.78
Units
Counts
Participants
OG00055
OG00158
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-2.5± 1.35
OG001-17.2± 1.34
Office DBP
Title
Measurements
OG000-0.7± 0.78
OG001-9.2± 0.77
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00057
OG00153
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-5.8± 1.68
OG001-16.1± 1.74
24-hour Mean DBP
Title
Measurements
OG000-3.2± 1.07
OG001-8.0± 1.11
Units
Counts
Participants
OG00060
OG00158
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-7.2± 1.82
OG001-15.5± 1.84
Office DBP
Title
Measurements
OG000-3.6± 1.13
OG001-7.8± 1.15
Units
Counts
Participants
OG00057
OG00153
Title
Denominators
Categories
Title
Measurements
OG000-2.3± 0.77
OG001-8.5± 0.80
Units
Counts
Participants
OG00060
OG00158
Title
Denominators
Categories
Title
Measurements
OG000-2.0± 0.67
OG001-9.5± 0.67
OG001
DB Period: Zilebesiran (Add-on to Indapamide)
Participants were randomized to receive zilebesiran, 600 milligrams (mg), as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to indapamide. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG00064
OG00163
Title
Denominators
Categories
Change in Daytime Mean SBP at Month 2
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-1.8± 1.54
OG001-15.9± 1.63
Change in Daytime Mean SBP at Month 3
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-5.3± 1.59
OG001
Change in Daytime Mean SBP at Month 6
ParticipantsOG00057
ParticipantsOG00153
Title
Measurements
OG000-6.5± 1.64
OG001
Change in Nighttime Mean SBP at Month 2
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-0.5± 1.44
OG001
Change in Nighttime Mean SBP at Month 3
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-2.9± 1.94
OG001
Change in Nighttime Mean SBP at Month 6
ParticipantsOG00057
ParticipantsOG00153
Title
Measurements
OG000-4.3± 2.07
OG001
Change in Daytime Mean DBP at Month 2
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-0.6± 0.95
OG001
Change in Daytime Mean DBP at Month 3
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-2.6± 0.91
OG001
Change in Daytime Mean DBP at Month 6
ParticipantsOG00057
ParticipantsOG00153
Title
Measurements
OG000-3.7± 1.09
OG001
Change in Nighttime Mean DBP at Month 2
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-0.4± 1.03
OG001
Change in Nighttime Mean DBP at Month 3
ParticipantsOG00061
ParticipantsOG00154
Title
Measurements
OG000-0.9± 1.12
OG001
Change in Nighttime Mean DBP at Month 6
ParticipantsOG00057
ParticipantsOG00153
Title
Measurements
OG000-1.8± 1.24
OG001
Units
Counts
Participants
OG00064
OG00163
Title
Denominators
Categories
Percent Change from Baseline at Week 2
ParticipantsOG00062
ParticipantsOG00160
Title
Measurements
OG0006.37± 29.27
OG001-91.99± 17.89
Percent Change from Baseline at Month 1
ParticipantsOG00061
ParticipantsOG00161
Title
Measurements
OG0001.90± 26.11
OG001
Percent Change from Baseline at Month 2
ParticipantsOG00061
ParticipantsOG00160
Title
Measurements
OG0004.34± 32.24
OG001
Percent Change from Baseline at Month 3
ParticipantsOG00061
ParticipantsOG00160
Title
Measurements
OG0004.86± 28.19
OG001
Percent Change from Baseline at Month 4
ParticipantsOG00061
ParticipantsOG00159
Title
Measurements
OG0001.81± 30.86
OG001
Percent Change from Baseline at Month 5
ParticipantsOG00060
ParticipantsOG00158
Title
Measurements
OG0001.23± 26.19
OG001
Percent Change from Baseline at Month 6
ParticipantsOG00059
ParticipantsOG00156
Title
Measurements
OG0004.81± 26.12
OG001
Units
Counts
Participants
OG000103
OG001112
Title
Denominators
Categories
Title
Measurements
OG000-1.4± 1.20
OG001-11.5± 1.16
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-10.2
Standard Error of the Mean
1.67
2-Sided
95
-13.4
-6.9
LS Mean Difference between zilebesiran (add on to amlodipine) and placebo (add on to amlodipine), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG000102
OG001103
Title
Denominators
Categories
Title
Measurements
OG000-1.8± 0.95
OG001-9.7± 0.97
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline 24-hour mean SBP assessed by ABPM and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-7.9
Standard Error of the Mean
1.36
2-Sided
95
-10.6
-5.3
LS Mean Difference between zilebesiran (add on to amlodipine) and placebo (add on to amlodipine), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG000113
OG001111
Title
Denominators
Categories
Title
Measurements
OG000-2.9± 0.82
OG001-11.5± 0.82
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for office SBP were included in the analysis for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-8.6
Standard Error of the Mean
1.16
2-Sided
95
-10.9
-6.3
LS Mean Difference between zilebesiran (add on to amlodipine) and placebo (add on to amlodipine), 95% CI was calculated using MMRM model.
Superiority
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000102
OG001103
Title
Denominators
Categories
Title
Measurements
OG00013.7
OG00139.8
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05.
Regression, Logistic
<0.0001
Logistic regression model included treatment and race (black or all other races) as factors and baseline 24-hour mean SBP and baseline eGFR as covariates.
Odds Ratio (OR)
5.08
2-Sided
95
2.43
10.61
Superiority
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000100
OG00199
Title
Denominators
Categories
Title
Measurements
OG000-0.8± 0.63
OG001-6.6± 0.64
Units
Counts
Participants
OG000103
OG001112
Title
Denominators
Categories
Title
Measurements
OG000-1.2± 0.84
OG001-6.2± 0.81
Units
Counts
Participants
OG000100
OG00199
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-0.9± 0.99
OG001-9.9± 1.00
24-hour Mean DBP
Title
Measurements
OG000-0.7± 0.56
OG001-6.4± 0.57
Units
Counts
Participants
OG000103
OG001112
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-1.4± 0.95
OG001-11.3± 0.96
Office DBP
Title
Measurements
OG000-0.6± 0.60
OG001-6.1± 0.61
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000102
OG001103
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-3.0± 1.26
OG001-9.0± 1.26
24-hour Mean DBP
Title
Measurements
OG000-1.6± 0.68
OG001-5.7± 0.68
Units
Counts
Participants
OG000113
OG001111
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-5.8± 1.12
OG001-12.6± 1.13
Office DBP
Title
Measurements
OG000-3.5± 0.74
OG001-6.7± 0.75
Units
Counts
Participants
OG000102
OG001103
Title
Denominators
Categories
Title
Measurements
OG000-1.1± 0.53
OG001-6.2± 0.54
Units
Counts
Participants
OG000113
OG001111
Title
Denominators
Categories
Title
Measurements
OG000-1.4± 0.52
OG001-6.2± 0.53
OG001
DB Period: Zilebesiran (Add-on to Amlodipine)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to amlodipine. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000120
OG001118
Title
Denominators
Categories
Change in Daytime Mean SBP at Month 2
ParticipantsOG000112
ParticipantsOG001108
Title
Measurements
OG000-2.2± 1.24
OG001-9.3± 1.26
Change in Daytime Mean SBP at Month 3
ParticipantsOG000110
ParticipantsOG001101
Title
Measurements
OG000-1.3± 1.14
OG001
Change in Daytime Mean SBP at Month 6
ParticipantsOG000102
ParticipantsOG001103
Title
Measurements
OG000-3.3± 1.31
OG001
Change in Nighttime Mean SBP at Month 2
ParticipantsOG000112
ParticipantsOG001108
Title
Measurements
OG0000.1± 1.31
OG001
Change in Nighttime Mean SBP at Month 3
ParticipantsOG000110
ParticipantsOG001101
Title
Measurements
OG0000.1± 1.34
OG001
Change in Nighttime Mean SBP at Month 6
ParticipantsOG000102
ParticipantsOG001103
Title
Measurements
OG000-2.6± 1.48
OG001
Change in Daytime Mean DBP at Month 2
ParticipantsOG000112
ParticipantsOG001108
Title
Measurements
OG000-0.8± 0.70
OG001
Change in Daytime Mean DBP at Month 3
ParticipantsOG000110
ParticipantsOG001101
Title
Measurements
OG000-0.8± 0.66
OG001
Change in Daytime Mean DBP at Month 6
ParticipantsOG000102
ParticipantsOG001103
Title
Measurements
OG000-1.5± 0.74
OG001
Change in Nighttime Mean DBP at Month 2
ParticipantsOG000112
ParticipantsOG001108
Title
Measurements
OG000-0.4± 0.76
OG001
Change in Nighttime Mean DBP at Month 3
ParticipantsOG000110
ParticipantsOG001101
Title
Measurements
OG000-0.4± 0.76
OG001
Change in Nighttime Mean DBP at Month 6
ParticipantsOG000102
ParticipantsOG001103
Title
Measurements
OG000-1.4± 0.84
OG001
Units
Counts
Participants
OG000120
OG001118
Title
Denominators
Categories
Percent Change from Baseline at Week 2
ParticipantsOG000116
ParticipantsOG001113
Title
Measurements
OG0002.67± 22.81
OG001-92.80± 15.99
Percent Change from Baseline at Month 1
ParticipantsOG000117
ParticipantsOG001112
Title
Measurements
OG0009.62± 35.83
OG001
Percent Change from Baseline at Month 2
ParticipantsOG000115
ParticipantsOG001111
Title
Measurements
OG00011.23± 35.17
OG001
Percent Change from Baseline at Month 3
ParticipantsOG000113
ParticipantsOG001109
Title
Measurements
OG00012.78± 34.90
OG001
Percent Change from Baseline at Month 4
ParticipantsOG000112
ParticipantsOG001112
Title
Measurements
OG00012.42± 41.83
OG001
Percent Change from Baseline at Month 5
ParticipantsOG000111
ParticipantsOG001107
Title
Measurements
OG00010.81± 37.94
OG001
Percent Change from Baseline at Month 6
ParticipantsOG000112
ParticipantsOG001109
Title
Measurements
OG0009.51± 48.05
OG001
Units
Counts
Participants
OG000117
OG001121
Title
Denominators
Categories
Title
Measurements
OG000-2.6± 1.25
OG001-9.3± 1.23
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in order the endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at nominal p-value < 0.05. Data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
MMRM
=0.0002
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-6.7
Standard Error of the Mean
1.76
2-Sided
95
-10.2
-3.3
LS Mean Difference between zilebesiran (add on to olmesartan) and placebo (add on to olmesartan), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG000128
OG001116
Title
Denominators
Categories
Title
Measurements
OG000-5.8± 0.99
OG001-7.6± 1.01
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for SBP assessed by ABPM, were included in the analysis for this endpoint.
MMRM
=0.2103
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline 24-hour mean SBP assessed by ABPM and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-1.8
Standard Error of the Mean
1.42
2-Sided
95
-4.6
1.0
LS Mean Difference between zilebesiran (add on to olmesartan) and placebo (add on to olmesartan), 95% CI was calculated using MMRM model.
Superiority
Units
Counts
Participants
OG000137
OG001134
Title
Denominators
Categories
Title
Measurements
OG000-6.3± 0.81
OG001-10.8± 0.81
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05. All collected data for office SBP were included in the analysis for this endpoint.
MMRM
<0.0001
MMRM model included treatment, visit, treatment-by-visit interaction, race (black or all other races) as fixed factors, with baseline office SBP and baseline eGFR as covariates. Unstructured covariance matrix was used.
Difference in LS Mean
-4.5
Standard Error of the Mean
1.14
2-Sided
95
-6.8
-2.3
LS Mean Difference between zilebesiran (add on to olmesartan) and placebo (add on to olmesartan), 95% CI was calculated using MMRM model.
Superiority
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000128
OG001116
Title
Denominators
Categories
Title
Measurements
OG00017.2
OG00125.9
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
A hierarchical testing procedure was used to control type I error at α=0.05 within each cohort and handle primary and key secondary endpoints analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at nominal p-value < 0.05.
Regression, Logistic
=0.1230
Logistic regression model included treatment and race (black or all other races) as factors and baseline 24-hour mean SBP and baseline eGFR as covariates.
Odds Ratio (OR)
1.67
2-Sided
95
0.87
3.23
Superiority
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000114
OG001115
Title
Denominators
Categories
Title
Measurements
OG000-1.4± 0.78
OG001-3.4± 0.78
Units
Counts
Participants
OG000117
OG001121
Title
Denominators
Categories
Title
Measurements
OG000-2.0± 0.86
OG001-5.3± 0.85
Units
Counts
Participants
OG000114
OG001115
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-2.2± 1.12
OG001-5.3± 1.13
24-hour Mean DBP
Title
Measurements
OG000-1.1± 0.63
OG001-2.3± 0.64
Units
Counts
Participants
OG000117
OG001121
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-2.4± 0.99
OG001-7.9± 0.97
Office DBP
Title
Measurements
OG000-1.2± 0.65
OG001-3.8± 0.64
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.
Units
Counts
Participants
OG000128
OG001116
Title
Denominators
Categories
24-hour Mean SBP
Title
Measurements
OG000-9.2± 1.24
OG001-8.3± 1.29
24-hour Mean DBP
Title
Measurements
OG000-5.2± 0.73
OG001-4.3± 0.76
Units
Counts
Participants
OG000137
OG001134
Title
Denominators
Categories
Office SBP
Title
Measurements
OG000-11.9± 1.33
OG001-12.4± 1.34
Office DBP
Title
Measurements
OG000-7.0± 0.76
OG001-7.1± 0.76
Units
Counts
Participants
OG000128
OG001116
Title
Denominators
Categories
Title
Measurements
OG000-3.1± 0.58
OG001-3.5± 0.59
Units
Counts
Participants
OG000137
OG001134
Title
Denominators
Categories
Title
Measurements
OG000-3.5± 0.53
OG001-5.8± 0.52
OG001
DB Period: Zilebesiran (Add-on to Olmesartan)
Participants were randomized to receive zilebesiran, 600 mg, as a SC injection, on Day 1 of the 6-month DB treatment period as an add-on therapy to olmesartan. Starting at Month 3, additional conventional oral antihypertensives ("escape antihypertensive medications") may be added to the participant's protocol-specified background antihypertensive medication per Investigator judgement.