Trial Outcomes & Findings for A Study to Evaluate Zilebesiran in Japanese Patients With Mild to Moderate Hypertension (NCT NCT06423352)

Last Updated: 2026-04-30

Results Overview

An AE is any untoward medical occurrence in a patient or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2026-04-30

Participant Flow

Participants with mild to moderate hypertension were enrolled at three (3) sites in Japan.

Participant milestones

Participant milestones
Measure	Zilebesiran 300 mg Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 600 mg Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
6-month Double-blind (DB) Period STARTED	12	12	12
6-month Double-blind (DB) Period COMPLETED	11	11	12
6-month Double-blind (DB) Period NOT COMPLETED	1	1	0
6-month Safety Follow-up Period STARTED	11	11	12
6-month Safety Follow-up Period COMPLETED	11	11	12
6-month Safety Follow-up Period NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Zilebesiran 300 mg Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 600 mg Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
6-month Double-blind (DB) Period Withdrawal by Subject	1	1	0

Baseline Characteristics

Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 Participants Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Total n=36 Participants Total of all reporting groups
Age, Categorical Age category (years), n (%) · <=18 years	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Age, Categorical Age category (years), n (%) · Between 18 and 65 years	12 Participants n=14 Participants	9 Participants n=34 Participants	9 Participants n=69 Participants	30 Participants n=140 Participants
Age, Categorical Age category (years), n (%) · >=65 years	0 Participants n=14 Participants	3 Participants n=34 Participants	3 Participants n=69 Participants	6 Participants n=140 Participants
Age, Continuous	58.5 Years n=14 Participants	54.5 Years n=34 Participants	58.5 Years n=69 Participants	58 Years n=140 Participants
Sex: Female, Male Sex (male or female), n (%) · Female	6 Participants n=14 Participants	5 Participants n=34 Participants	1 Participants n=69 Participants	12 Participants n=140 Participants
Sex: Female, Male Sex (male or female), n (%) · Male	6 Participants n=14 Participants	7 Participants n=34 Participants	11 Participants n=69 Participants	24 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · American Indian or Alaska Native	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · Asian	12 Participants n=14 Participants	12 Participants n=34 Participants	12 Participants n=69 Participants	36 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · Black or African American	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · White	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · More than one race	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Race, n (%) · Unknown or Not Reported	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
24-hour Mean Blood Pressure by Ambulatory Blood Pressure Monitoring (ABPM) Baseline Systolic Blood Pressure (SBP; Actual)	143.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.2 • n=14 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	138.9 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.0 • n=34 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	137.7 millimeters of mercury (mmHg) STANDARD_DEVIATION 6.8 • n=69 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	140.1 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.4 • n=140 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.
24-hour Mean Blood Pressure by Ambulatory Blood Pressure Monitoring (ABPM) Baseline Diastolic Blood Pressure (DBP; Actual)	87.2 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.2 • n=14 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	86.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.2 • n=34 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	85.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 5.4 • n=69 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	86.4 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.2 • n=140 Participants • Full Analysis Set (FAS): All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.
Mean Office Blood Pressure (OBP) Baseline SBP (Actual)	139.8 mmHg STANDARD_DEVIATION 11.5 • n=14 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	134.3 mmHg STANDARD_DEVIATION 9.4 • n=34 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	133.9 mmHg STANDARD_DEVIATION 8.5 • n=69 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	136 mmHg STANDARD_DEVIATION 10 • n=140 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.
Mean Office Blood Pressure (OBP) Baseline DBP (Actual)	88.3 mmHg STANDARD_DEVIATION 7.4 • n=14 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	86.6 mmHg STANDARD_DEVIATION 8.3 • n=34 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	89.2 mmHg STANDARD_DEVIATION 6.3 • n=69 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.	88 mmHg STANDARD_DEVIATION 7.3 • n=140 Participants • FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm.

PRIMARY outcome

Timeframe: Up to 12 months

Population: SAS: All participants who received any amount of zilebesiran or placebo during the study.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 Participants Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Number of Participants With Adverse Events (AEs) Severe Treatment-emergent AEs, n (%)	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Treatment-emergent AEs Leading to Withdrawal from Study, n (%)	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Death (any fatal SAE), n (%)	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Treatment-emergent AEs, n (%)	6 Participants	4 Participants	6 Participants
Number of Participants With Adverse Events (AEs) Related Treatment-emergent AEs, n (%)	1 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Treatment-emergent SAEs, n (%)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Month 3 and Month 6

Population: Pharmacodynamic (PD) Analysis Set: 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 analysis. Number analyzed is the number of participants with data available for analysis at the specified time-points.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 Participants Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=11 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Percent Change From Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6 Month 3 (% Change from Baseline)	-96.85 Percent Change Standard Deviation 2.32	6.93 Percent Change Standard Deviation 21.93	-96.85 Percent Change Standard Deviation 1.45
Percent Change From Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6 Month 6 (% Change from Baseline)	-95.79 Percent Change Standard Deviation 3.21	-2.74 Percent Change Standard Deviation 12.75	-95.36 Percent Change Standard Deviation 2.17

SECONDARY outcome

Timeframe: Baseline and Month 3 and Month 6

Population: FAS: All randomized participants who received any amount of study drug. All by-treatment analyses based on the FAS were grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time-points.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 Participants Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=11 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM Month 3 SBP (Change from Baseline)	-17.8 mmHg Standard Deviation 11.8	0.4 mmHg Standard Deviation 7.8	-15.2 mmHg Standard Deviation 9.0
Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM Month 6 SBP (Change from Baseline)	-12.2 mmHg Standard Deviation 11.7	-6.5 mmHg Standard Deviation 11.0	-12.6 mmHg Standard Deviation 4.8
Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM Month 3 DBP (Change from Baseline)	-9.2 mmHg Standard Deviation 6.5	0.3 mmHg Standard Deviation 5.3	-8.6 mmHg Standard Deviation 6.0
Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM Month 6 DBP (Change from Baseline)	-8.2 mmHg Standard Deviation 6.0	-3.9 mmHg Standard Deviation 6.6	-7.1 mmHg Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline and Month 3 and Month 6

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 Participants Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=11 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP Month 3 SBP (Change from Baseline)	-14.4 mmHg Standard Deviation 12.3	4.4 mmHg Standard Deviation 5.0	-14.4 mmHg Standard Deviation 21.0
Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP Month 6 SBP (Change from Baseline)	-6.8 mmHg Standard Deviation 9.6	1.2 mmHg Standard Deviation 13.3	-10.3 mmHg Standard Deviation 12.9
Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP Month 3 DBP (Change from Baseline)	-7.4 mmHg Standard Deviation 8.0	0.1 mmHg Standard Deviation 5.2	-7.8 mmHg Standard Deviation 10.4
Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP Month 6 DBP (Change from Baseline)	-1.7 mmHg Standard Deviation 6.8	-2.2 mmHg Standard Deviation 7.1	-4.5 mmHg Standard Deviation 7.9

SECONDARY outcome

Timeframe: Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.

Population: Pharmacokinetic (PK) Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment.

Cmax is the highest concentration of zilebesiran in the plasma and metabolite after a dose is given.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Maximum Plasma Concentration (Cmax) of Zilebesiran and Its Metabolite Zilebesiran Plasma PK	2445 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 42.4	—	1024 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.5
Maximum Plasma Concentration (Cmax) of Zilebesiran and Its Metabolite Metabolite [AS(N-1)3'] Plasma PK	288.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 49.7	—	101.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 72.1

SECONDARY outcome

Timeframe: Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.

Population: PK Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time-points.

Tmax is the time it takes for zilebesiran to reach the Cmax after administration.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite Zilebesiran Plasma PK	6.00 Hours Interval 1.0 to 16.0	—	3.53 Hours Interval 1.0 to 12.0
Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite Metabolite [AS(N-1)3'] Plasma PK	16.00 Hours Interval 4.0 to 16.0	—	8.01 Hours Interval 3.0 to 16.0

SECONDARY outcome

Timeframe: Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.

t½ is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=11 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=10 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite Zilebesiran Plasma PK	5.56 Hours Geometric Coefficient of Variation 36.9	—	5.83 Hours Geometric Coefficient of Variation 65.3
Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite Metabolite [AS(N-1)3'] Plasma PK	5.48 Hours Geometric Coefficient of Variation 25.6	—	9.42 Hours Geometric Coefficient of Variation 120.8

SECONDARY outcome

Timeframe: Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose.

Population: PK Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment.

AUClast is the AUC from the time of dosing to the last measurable concentration of the drug.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite Zilebesiran Plasma PK	41260 ng*h/mL Geometric Coefficient of Variation 32.2	—	16150 ng*h/mL Geometric Coefficient of Variation 43.5
Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite Metabolite [AS(N-1)3'] Plasma PK	4906 ng*h/mL Geometric Coefficient of Variation 47.5	—	1587 ng*h/mL Geometric Coefficient of Variation 73.8

SECONDARY outcome

Timeframe: Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose.

Population: PK Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment.

Outcome measures

Outcome measures
Measure	Zilebesiran 600 mg n=12 Participants Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 300 mg n=12 Participants Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Pooled Urine PK (fe) of Zilebesiran and Its Metabolite Zilebesiran Urine PK	30.08 Percent Geometric Coefficient of Variation 16.1	—	23.62 Percent Geometric Coefficient of Variation 21.2
Pooled Urine PK (fe) of Zilebesiran and Its Metabolite Metabolite [AS(N-1)3'] Urine PK	3.85 Percent Geometric Coefficient of Variation 28.3	—	2.68 Percent Geometric Coefficient of Variation 42.7

Adverse Events

Zilebesiran 300 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Zilebesiran 600 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc.

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 1. Copy of disclosure is provided to Sponsor at least 60 days before submission for publication or date of disclosure 2. Confidential information is deleted if requested by Sponsor 3. If a Discovery is disclosed, defer publication or disclosure for 60 days from time Sponsor notifies them of its wish to file a patent application on such Discovery 4. Site/Investigator will not disclose or publish results until results from all sites have been received and analyzed by Sponsor
Publication restrictions are in place

Restriction type: OTHER

Measure	Zilebesiran 300 mg n=12 participants at risk Participants were administered a single dose of zilebesiran (300 mg) by subcutaneous (SC) injection on Day 1 of the 6-month Double-blind (DB) period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Zilebesiran 600 mg n=12 participants at risk Participants were administered a single dose of zilebesiran (600 mg) by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.	Placebo n=12 participants at risk Participants were administered a single dose of placebo by SC injection on Day 1 of the 6-month DB period. After the DB period, participants completed safety follow-up visits at Months 9 and 12.
Musculoskeletal and connective tissue disorders Periarthritis	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Eye disorders Eye pruritus	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Gastrointestinal disorders Gastralgia	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Gastrointestinal disorders Nausea	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Infections and infestations COVID-19	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Infections and infestations Influenza	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	16.7% 2/12 • Number of events 2 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Infections and infestations Pharyngitis	16.7% 2/12 • Number of events 2 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Investigations Alanine aminotrasferase increased	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Investigations Blood potassium increased	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Investigations Gamma-glutamyltransferase increased	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 2 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Investigations Glomerular filtration rate decreased	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Nervous system disorders Headache	16.7% 2/12 • Number of events 2 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Reproductive system and breast disorders Vaginal hemorrhage	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.
Skin and subcutaneous tissue disorders Eczema	8.3% 1/12 • Number of events 1 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.	0.00% 0/12 • Up to 12 months SAS: All participants who received any amount of zilebesiran or placebo during the study.