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The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacodynamics (PD) and pharmacokinetics (PK) of zilebesiran in Japanese patients with mild to moderate hypertension.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zilebesiran | Experimental | Participants will be administered a single dose of zilebesiran. |
|
| Placebo | Placebo Comparator | Participants will be administered a single dose of placebo. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zilebesiran | Drug | Zilebesiran administered by subcutaneous (SC) injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 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. | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6 | Baseline and Month 3 and Month 6 | |
| Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM | Baseline and Month 3 and Month 6 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Fukuoka | Japan | ||||
| Clinical Trial Site |
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.
Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more.
Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.
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Participants with mild to moderate hypertension were enrolled at three (3) sites in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6-month Double-blind (DB) Period |
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| 6-month Safety Follow-up Period |
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Safety Analysis Set (SAS): All participants who received any amount of study drug. All by-treatment analyses based on the Safety Analysis Set were grouped according to the treatment actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Zilebesiran 600 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) | 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. | SAS: All participants who received any amount of zilebesiran or placebo during the study. | Posted | Count of Participants | Participants | Up to 12 months |
|
Up to 12 months
SAS: All participants who received any amount of zilebesiran or placebo during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye pruritus | Eye disorders | MedDRA27.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Alnylam Pharmaceuticals Inc. | 866-330-0326 | clinicaltrials@alnylam.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 18, 2024 | Apr 10, 2026 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 20, 2025 | Apr 10, 2026 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| Placebo | Drug | Placebo administered by SC injection |
|
| Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP | Baseline and Month 3 and Month 6 |
| Maximum Plasma Concentration (Cmax) of Zilebesiran and Its Metabolite | Cmax is the highest concentration of zilebesiran in the plasma and metabolite after a dose is given. | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
| Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite | Tmax is the time it takes for zilebesiran to reach the Cmax after administration. | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
| Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite | t½ is the time it takes for the concentration of the drug in the plasma to be reduced by 50%. | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
| Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite | AUClast is the AUC from the time of dosing to the last measurable concentration of the drug. | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
| Pooled Urine PK (fe) of Zilebesiran and Its Metabolite | Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose. |
| Osaka |
| Japan |
| Clinical Trial Site | Tokyo | Japan |
| NOT COMPLETED |
|
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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 24-hour Mean Blood Pressure by Ambulatory Blood Pressure Monitoring (ABPM) | 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 | Standard Deviation | millimeters of mercury (mmHg) |
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| Mean Office Blood Pressure (OBP) | 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 | Standard Deviation | mmHg |
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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. |
| OG002 | 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. |
|
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| Secondary | Percent Change From Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6 | 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. | Posted | Mean | Standard Deviation | Percent Change | Baseline and Month 3 and Month 6 |
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| Secondary | Change From Baseline at Month 3 and Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline and Month 3 and Month 6 |
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| Secondary | Change From Baseline at Month 3 and Month 6 in SBP and DBP Assessed by OBP | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline and Month 3 and Month 6 |
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| Secondary | Maximum Plasma Concentration (Cmax) of Zilebesiran and Its Metabolite | Cmax is the highest concentration of zilebesiran in the plasma and metabolite after a dose is given. | Pharmacokinetic (PK) Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
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|
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite | Tmax is the time it takes for zilebesiran to reach the Cmax after administration. | 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. | Posted | Median | Full Range | Hours | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
|
|
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| Secondary | Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite | t½ is the time it takes for the concentration of the drug in the plasma to be reduced by 50%. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
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| Secondary | Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite | AUClast is the AUC from the time of dosing to the last measurable concentration of the drug. | PK Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. |
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| Secondary | Pooled Urine PK (fe) of Zilebesiran and Its Metabolite | PK Analysis Set: All participants who received at least 1 full dose of zilebesiran and had at least 1 evaluable postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percent | Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose. |
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| 0 |
| 12 |
| 0 |
| 12 |
| 6 |
| 12 |
| EG001 | 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. | 0 | 12 | 0 | 12 | 6 | 12 |
| EG002 | 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. | 0 | 12 | 0 | 12 | 4 | 12 |
| Gastralgia | Gastrointestinal disorders | MedDRA27.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA27.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA27.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA27.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA27.0 | Systematic Assessment |
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| Alanine aminotrasferase increased | Investigations | MedDRA27.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA27.0 | Systematic Assessment |
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| Blood potassium increased | Investigations | MedDRA27.0 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA27.0 | Systematic Assessment |
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| Glomerular filtration rate decreased | Investigations | MedDRA27.0 | Systematic Assessment |
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| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA27.0 | Systematic Assessment |
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| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA27.0 | Systematic Assessment |
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| Vaginal hemorrhage | Reproductive system and breast disorders | MedDRA27.0 | Systematic Assessment |
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| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA27.0 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA27.0 | Systematic Assessment |
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| Month 6 SBP (Change from Baseline) |
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| Month 3 DBP (Change from Baseline) |
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| Month 6 DBP (Change from Baseline) |
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| Month 3 DBP (Change from Baseline) |
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| Month 6 DBP (Change from Baseline) |
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| Metabolite [AS(N-1)3'] Plasma PK |
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