Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension (NCT NCT04936035)

NCT ID: NCT04936035

Last Updated: 2024-12-27

Results Overview

24-hour ABPM 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 mean was the average of BP by 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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 394 participants
• Primary outcome timeframe: Baseline and Month 3
• Results posted on: 2024-12-27

Participant Flow

A total of 86 clinical sites across North America (including 76 in the US and 10 in Canada) and 25 sites in Europe (5 in the United Kingdom and 20 in Ukraine) enrolled 394 participants in this study. This study is still ongoing, and the data collected up to the primary completion date (i.e., Month 6 of the double-blind (DB) period) for the participant flow are reported here.

A total of 394 participants were initially enrolled in this study. 16 participants enrolled in Ukraine were unable to continue participation due to geopolitical instability. Due to the challenge of data collection and cleaning, these participants were excluded from the analysis sets used in this study. Therefore, results are presented for 378 randomized participants.

Participant milestones

Measure	Placebo Participants received zilebesiran matching placebo, as subcutaneous (SC) injection, once every 3 months (Q3M) during the 6-month DB period.	Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M) Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M Participants received zilebesiran, 300 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q3M Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Overall Study STARTED	76	78	73	75	76
Overall Study COMPLETED	70	70	70	68	69
Overall Study NOT COMPLETED	6	8	3	7	7

Reasons for withdrawal

Measure	Placebo Participants received zilebesiran matching placebo, as subcutaneous (SC) injection, once every 3 months (Q3M) during the 6-month DB period.	Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M) Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M Participants received zilebesiran, 300 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q3M Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Overall Study Adverse Event	0	1	0	0	0
Overall Study Death	0	0	0	1	0
Overall Study Lost to Follow-up	0	1	1	2	1
Overall Study Physician Decision	0	1	0	0	0
Overall Study Protocol Deviation	0	0	1	0	0
Overall Study Subject Stopped Participation in the Study	5	5	1	2	3
Overall Study Reason Unknown	0	0	0	0	1
Overall Study Withdrawal by Subject	1	0	0	0	0
Overall Study Discontinued Treatment due to Participant's Decision but Ongoing in Safety Follow-up	0	0	0	2	0
Overall Study Discontinued Treatment due to Physician Decision but Ongoing in Safety Follow-up	0	0	0	0	1
Overall Study Discontinued Treatment due to Adverse Event but Ongoing in Safety Follow-up	0	0	0	0	1

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension

Baseline characteristics by cohort

Measure	Placebo n=75 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M during the 6-month DB period.	Zilebesiran 150 mg Q6M n=78 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M n=73 Participants Participants received zilebesiran, 300 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q3M n=75 Participants Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 600 mg Q6M n=76 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Total n=377 Participants Total of all reporting groups
Age, Continuous	56.8 years STANDARD_DEVIATION 11.2 • n=5 Participants	55.5 years STANDARD_DEVIATION 10.6 • n=7 Participants	56.4 years STANDARD_DEVIATION 10.3 • n=5 Participants	57.7 years STANDARD_DEVIATION 10.6 • n=4 Participants	57.4 years STANDARD_DEVIATION 10.2 • n=21 Participants	56.8 years STANDARD_DEVIATION 10.6 • n=8 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	39 Participants n=7 Participants	29 Participants n=5 Participants	30 Participants n=4 Participants	31 Participants n=21 Participants	167 Participants n=8 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	39 Participants n=7 Participants	44 Participants n=5 Participants	45 Participants n=4 Participants	45 Participants n=21 Participants	210 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	19 Participants n=7 Participants	16 Participants n=5 Participants	10 Participants n=4 Participants	20 Participants n=21 Participants	74 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=5 Participants	59 Participants n=7 Participants	57 Participants n=5 Participants	65 Participants n=4 Participants	56 Participants n=21 Participants	303 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants	5 Participants n=21 Participants	23 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	19 Participants n=4 Participants	19 Participants n=21 Participants	93 Participants n=8 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	53 Participants n=7 Participants	54 Participants n=5 Participants	48 Participants n=4 Participants	52 Participants n=21 Participants	259 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
24-hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM)	141.1 millimeter of mercury (mmHg) STANDARD_DEVIATION 7.9 • n=5 Participants	140.6 millimeter of mercury (mmHg) STANDARD_DEVIATION 8.5 • n=7 Participants	142.5 millimeter of mercury (mmHg) STANDARD_DEVIATION 8.8 • n=5 Participants	141.6 millimeter of mercury (mmHg) STANDARD_DEVIATION 7.7 • n=4 Participants	143.1 millimeter of mercury (mmHg) STANDARD_DEVIATION 9.0 • n=21 Participants	141.8 millimeter of mercury (mmHg) STANDARD_DEVIATION 8.4 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Month 3

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in the SAP, for assessment of Month 3 outcome measures, zilebesiran 300mg Q3M and 300mg Q6M were pooled together.

24-hour ABPM 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 mean was the average of BP by 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.

Outcome measures

Measure	Placebo n=60 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=68 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=137 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=65 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM	6.8 mmHg Standard Error 1.58	-7.3 mmHg Standard Error 1.49	-10.0 mmHg Standard Error 1.05	-8.9 mmHg Standard Error 1.52	—

SECONDARY outcome

Timeframe: Baseline and Month 3

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in the SAP, for assessment of Month 3 outcome measures, zilebesiran 300mg Q3M and 300mg Q6M were pooled together.

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.

Outcome measures

Measure	Placebo n=60 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=68 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=133 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=64 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 3 in Mean Sitting Office SBP	-0.1 mmHg Standard Error 1.57	-9.7 mmHg Standard Error 1.49	-12.1 mmHg Standard Error 1.06	-9.2 mmHg Standard Error 1.52	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

24-hour ABPM 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 mean was the average of blood pressure (BP) by 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.

Outcome measures

Measure	Placebo n=54 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=62 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=60 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=63 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM	4.6 mmHg Standard Error 1.73	-6.5 mmHg Standard Error 1.63	-9.9 mmHg Standard Error 1.58	-9.5 mmHg Standard Error 1.65	-9.6 mmHg Standard Error 1.62

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

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.

Outcome measures

Measure	Placebo n=57 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=65 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=57 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=62 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 6 in Mean Sitting Office SBP	-0.6 mmHg Standard Error 1.80	-8.2 mmHg Standard Error 1.70	-11.1 mmHg Standard Error 1.67	-12.8 mmHg Standard Error 1.80	-10.8 mmHg Standard Error 1.73

SECONDARY outcome

Timeframe: Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug.

24-hour ABPM 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 mean was the average of blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means.

Outcome measures

Measure	Placebo n=75 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=78 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=73 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=75 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=76 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Percentage of Participants With 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction of ≥20 mmHg From Baseline Without Additional Antihypertensive Medications at Month 6	6.7 percentage of participants	30.8 percentage of participants	50.7 percentage of participants	38.7 percentage of participants	47.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Month 3

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in the SAP, for assessment of Month 3 outcome measures, zilebesiran 300mg Q3M and 300mg Q6M were pooled together.

24-hour ABPM 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 mean was the average of blood pressure (BP) by 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.

Outcome measures

Measure	Placebo n=60 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=68 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=137 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=65 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 3 in 24-hour Mean DBP Assessed by ABPM	3.5 mmHg Standard Error 0.87	-4.5 mmHg Standard Error 0.82	-5.7 mmHg Standard Error 0.58	-5.8 mmHg Standard Error 0.84	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

24-hour ABPM 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 mean was the average of blood pressure (BP) by 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

Outcome measures

Measure	Placebo n=54 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=62 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=60 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=63 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 6 in 24-hour Mean DBP Assessed by ABPM	2.2 mmHg Standard Error 0.97	-4.8 mmHg Standard Error 0.91	-6.1 mmHg Standard Error 0.89	-6.3 mmHg Standard Error 0.93	-6.3 mmHg Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline and Month 3

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in the SAP, for assessment of Month 3 outcome measures, zilebesiran 300mg Q3M and 300mg Q6M were pooled together.

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.

Outcome measures

Measure	Placebo n=60 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=68 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=133 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=64 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 3 in Mean Sitting Office DBP	-0.6 mmHg Standard Error 1.00	-5.3 mmHg Standard Error 0.94	-7.0 mmHg Standard Error 0.67	-5.4 mmHg Standard Error 0.97	—

SECONDARY outcome

Timeframe: Baseline and Month 3

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in the SAP, for assessment of Month 3 outcome measures, zilebesiran 300mg Q3M and 300mg Q6M were pooled together.

Time adjusted change from baseline in mean sitting office SBP and DBP was the area under the curve (AUC) between Month 1 and 3 visits divided by the duration of time period.

Outcome measures

Measure	Placebo n=60 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=68 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=133 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=64 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP Office SBP	-0.6 mmHg Standard Error 1.29	-9.1 mmHg Standard Error 1.24	-10.9 mmHg Standard Error 0.89	-10.1 mmHg Standard Error 1.26	—
Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP Office DBP	-0.0 mmHg Standard Error 0.80	-4.8 mmHg Standard Error 0.77	-6.5 mmHg Standard Error 0.55	-6.0 mmHg Standard Error 0.78	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

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.

Outcome measures

Measure	Placebo n=57 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=65 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=57 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=62 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline at Month 6 in Mean Sitting Office DBP	-1.2 mmHg Standard Error 1.20	-4.1 mmHg Standard Error 1.13	-6.8 mmHg Standard Error 1.12	-8.2 mmHg Standard Error 1.20	-5.0 mmHg Standard Error 1.16

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

Time adjusted change from baseline through Month 6 in 24-hour mean SBP and DBP was determined as the AUC between Month 1 and 6 visits divided by the duration of the time period.

Outcome measures

Measure	Placebo n=54 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=62 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=60 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=63 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM 24-hour Mean SBP	5.8 mmHg Standard Error 1.26	-6.3 mmHg Standard Error 1.20	-9.2 mmHg Standard Error 1.20	-9.6 mmHg Standard Error 1.22	-9.1 mmHg Standard Error 1.22
Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM 24-hour Mean DBP	3.1 mmHg Standard Error 0.72	-4.2 mmHg Standard Error 0.69	-5.5 mmHg Standard Error 0.69	-5.8 mmHg Standard Error 0.70	-5.9 mmHg Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses.

Time adjusted change is the AUC between Month 1 and 6 visits divided by the duration of time period.

Outcome measures

Measure	Placebo n=57 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=65 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=68 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=57 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=62 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP Office SBP	-0.5 mmHg Standard Error 1.25	-9.0 mmHg Standard Error 1.20	-12.1 mmHg Standard Error 1.21	-11.0 mmHg Standard Error 1.24	-10.0 mmHg Standard Error 1.22
Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP Office DBP	-0.6 mmHg Standard Error 0.80	-4.7 mmHg Standard Error 0.76	-7.2 mmHg Standard Error 0.77	-6.7 mmHg Standard Error 0.79	-5.5 mmHg Standard Error 0.78

SECONDARY outcome

Timeframe: Baseline, and Months 1, 3 and 6

Population: The Full Analysis Set included all randomized participants who received any amount of the study drug. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at specified timepoints.

ABPM 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). Baseline was defined as the last assessment prior to receiving the first dose of study drug. LS mean and SE were calculated using a MMRM approach.

Outcome measures

Measure	Placebo n=67 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=72 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=70 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=71 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=69 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean SBP at Month 3	7.0 mmHg Standard Error 1.85	-6.4 mmHg Standard Error 1.76	-8.2 mmHg Standard Error 1.74	-9.7 mmHg Standard Error 1.77	-8.5 mmHg Standard Error 1.79
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean SBP at Month 6	4.7 mmHg Standard Error 1.86	-5.8 mmHg Standard Error 1.75	-8.9 mmHg Standard Error 1.69	-10.2 mmHg Standard Error 1.78	-11.1 mmHg Standard Error 1.74
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean DBP at Month 1	2.9 mmHg Standard Error 0.91	-2.7 mmHg Standard Error 0.88	-4.0 mmHg Standard Error 0.91	-5.9 mmHg Standard Error 0.89	-5.8 mmHg Standard Error 0.89
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean DBP at Month 3	3.5 mmHg Standard Error 0.94	-4.8 mmHg Standard Error 0.89	-6.1 mmHg Standard Error 0.88	-5.7 mmHg Standard Error 0.90	-5.6 mmHg Standard Error 0.90
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean DBP at Month 6	2.1 mmHg Standard Error 1.07	-4.8 mmHg Standard Error 1.01	-6.2 mmHg Standard Error 0.98	-6.1 mmHg Standard Error 1.02	-5.7 mmHg Standard Error 1.00
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean DBP at Month 1	3.2 mmHg Standard Error 1.01	-2.4 mmHg Standard Error 0.98	-3.5 mmHg Standard Error 1.02	-5.9 mmHg Standard Error 0.99	-5.4 mmHg Standard Error 1.00
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean DBP at Month 3	3.7 mmHg Standard Error 1.08	-3.6 mmHg Standard Error 1.02	-5.1 mmHg Standard Error 1.01	-4.8 mmHg Standard Error 1.03	-5.8 mmHg Standard Error 1.04
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean DBP at Month 6	2.2 mmHg Standard Error 1.09	-4.3 mmHg Standard Error 1.03	-5.9 mmHg Standard Error 1.00	-6.7 mmHg Standard Error 1.05	-7.6 mmHg Standard Error 1.03
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean SBP at Month 1	4.3 mmHg Standard Error 1.50	-3.6 mmHg Standard Error 1.45	-6.4 mmHg Standard Error 1.51	-9.6 mmHg Standard Error 1.46	-9.1 mmHg Standard Error 1.48
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean SBP at Month 3	6.7 mmHg Standard Error 1.62	-7.6 mmHg Standard Error 1.53	-10.7 mmHg Standard Error 1.52	-9.8 mmHg Standard Error 1.54	-8.9 mmHg Standard Error 1.56
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Daytime Mean SBP at Month 6	4.5 mmHg Standard Error 1.83	-6.9 mmHg Standard Error 1.72	-10.4 mmHg Standard Error 1.66	-9.3 mmHg Standard Error 1.74	-8.8 mmHg Standard Error 1.71
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit Change in Nighttime Mean SBP at Month 1	4.7 mmHg Standard Error 1.64	-3.4 mmHg Standard Error 1.59	-5.1 mmHg Standard Error 1.64	-9.5 mmHg Standard Error 1.60	-8.0 mmHg Standard Error 1.62

SECONDARY outcome

Timeframe: Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6

Population: Pharmacodynamic (PD) Analysis Set included all participants who received at least 1 full dose of study drug. All by-treatment analyses based on the PD Analysis Set were grouped according to the treatment actually received. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at specified timepoints.

Outcome measures

Measure	Placebo n=74 Participants Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=78 Participants Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M and Q3M n=73 Participants Participants received zilebesiran, 300 mg, as SC injection, Q6M or Q3M during the 6-month DB period. Participants assigned to the Q6M regimen received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=75 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 600 mg Q6M n=76 Participants Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Week 2	-0.05 percent change Standard Deviation 23.99	-88.34 percent change Standard Deviation 9.96	-92.68 percent change Standard Deviation 4.40	-92.77 percent change Standard Deviation 4.03	-94.49 percent change Standard Deviation 5.52
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 1	1.61 percent change Standard Deviation 22.96	-94.48 percent change Standard Deviation 9.04	-97.38 percent change Standard Deviation 1.72	-97.20 percent change Standard Deviation 2.30	-98.22 percent change Standard Deviation 2.69
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 2	-2.06 percent change Standard Deviation 21.87	-94.47 percent change Standard Deviation 12.38	-97.74 percent change Standard Deviation 2.04	-97.64 percent change Standard Deviation 2.15	-98.70 percent change Standard Deviation 0.74
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 3	-2.19 percent change Standard Deviation 22.86	-93.31 percent change Standard Deviation 9.94	-97.26 percent change Standard Deviation 2.78	-97.00 percent change Standard Deviation 2.61	-98.25 percent change Standard Deviation 1.60
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 4	1.39 percent change Standard Deviation 26.06	-91.89 percent change Standard Deviation 11.61	-95.94 percent change Standard Deviation 5.23	-98.38 percent change Standard Deviation 1.08	-97.98 percent change Standard Deviation 1.74
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 5	-2.27 percent change Standard Deviation 21.18	-90.10 percent change Standard Deviation 12.48	-94.85 percent change Standard Deviation 6.58	-98.23 percent change Standard Deviation 1.13	-97.38 percent change Standard Deviation 2.41
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6 Percent Change from Baseline at Month 6	-4.97 percent change Standard Deviation 24.90	-87.84 percent change Standard Deviation 13.82	-93.13 percent change Standard Deviation 8.29	-97.71 percent change Standard Deviation 1.91	-96.41 percent change Standard Deviation 4.04

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Zilebesiran 150 mg Q6M

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Zilebesiran 300 mg Q6M

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Zilebesiran 300 mg Q3M

Serious events: 4 serious events

Other events: 23 other events

Deaths: 1 deaths

Zilebesiran 600 mg Q6M

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=75 participants at risk Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=78 participants at risk Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M n=73 participants at risk Participants received zilebesiran, 300 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q3M n=75 participants at risk Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 600 mg Q6M n=76 participants at risk Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
Infections and infestations Pyelonephritis	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Infections and infestations Endocarditis	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Cardiac disorders Acute coronary syndrome	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Cardiac disorders Coronary artery disease	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Gastrointestinal disorders Colitis	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.4% 1/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Injury, poisoning and procedural complications Coronary bypass stenosis	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage II	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Nervous system disorders Dizziness	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Nervous system disorders Transient ischaemic attack	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Psychiatric disorders Abnormal behaviour	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Vascular disorders Aortic aneurysm	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Vascular disorders Hypertension	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Vascular disorders Hypertensive urgency	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Vascular disorders Orthostatic hypotension	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.

Other adverse events

Measure	Placebo n=75 participants at risk Participants received zilebesiran matching placebo, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 150 mg Q6M n=78 participants at risk Participants received zilebesiran, 150 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q6M n=73 participants at risk Participants received zilebesiran, 300 mg, as SC injection on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.	Zilebesiran 300 mg Q3M n=75 participants at risk Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month DB period.	Zilebesiran 600 mg Q6M n=76 participants at risk Participants received zilebesiran, 600 mg, as SC injection, on Day 1 and Month 6 of the 6-month DB period. They received placebo at Month 3 of the 6-month DB period to maintain the blind.
General disorders Injection site reaction	0.00% 0/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	3.8% 3/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.5% 4/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	10.7% 8/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.3% 4/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Infections and infestations Coronavirus Disease of 2019 (COVID-19)	4.0% 3/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	3.8% 3/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	8.2% 6/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	8.0% 6/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.3% 4/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Infections and infestations Upper respiratory tract infection	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	3.8% 3/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.5% 4/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.7% 2/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Metabolism and nutrition disorders Hyperkalaemia	1.3% 1/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	6.4% 5/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.5% 4/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	6.7% 5/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	6.6% 5/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 2/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.6% 2/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.5% 4/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.7% 2/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Nervous system disorders Dizziness	5.3% 4/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.6% 2/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.7% 2/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	4.0% 3/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	3.9% 3/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Nervous system disorders Headache	9.3% 7/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.5% 4/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	2.7% 2/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	1.3% 1/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.
Vascular disorders Hypertension	6.7% 5/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	5.1% 4/78 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	0.00% 0/73 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	4.0% 3/75 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.	6.6% 5/76 • Baseline up to Month 6 Safety Analysis Set included all participants who received any amount of study drug, grouped according to the treatment actually received. This study is still ongoing, and the data collected up to the primary completion date (i.e., up to Month 6) are reported here. Data will be updated 1 year after the study completion date.

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals

Phone: 866-330-0326

Email: clinicaltrials@alnylam.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER