Mild to Moderate Hypertension
Conditions
Keywords
High blood pressure, Hypertension, Hypertensive, siRNA, Angiotensinogen, AGT
Brief summary
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.
Interventions
DRUGZilebesiran
Zilebesiran administered by subcutaneous (SC) injection
DRUGPlacebo
Placebo administered by SC injection
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Must have been born in Japan, and their biological parents and grandparents must have been of Japanese origin * Has mean systolic office blood pressure (SBP) of \>130 and \<=165 mmHg by automated office blood pressure measurement, after a minimum of 3 weeks of washout if taking hypertensive medication * Has 24-hour mean SBP ≥130 mmHg by ambulatory blood pressure monitoring (ABPM), without antihypertensive medication
Exclusion criteria
* Has secondary hypertension, symptomatic orthostatic hypotension * Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2× upper limit of normal (ULN) * Has elevated serum potassium \>5 mmol/L * Has estimated glomerular filtration rate (eGFR) of \<60 mL/min/1.73m\^2 * Has received an investigational agent within the last 30 days * Has Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus or newly diagnosed Type 2 diabetes mellitus * Has history of intolerance to SC injection(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. | Cmax is the highest concentration of zilebesiran in the plasma and metabolite after a dose is given. |
| Time to Maximum Plasma Concentration (Tmax) of Zilebesiran and Its Metabolite | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. | Tmax is the time it takes for zilebesiran to reach the Cmax after administration. |
| Elimination Half-life (t1/2) of Zilebesiran and Its Metabolite | 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%. |
| Area Under the Curve (AUClast) of Zilebesiran and Its Metabolite | Predose and 30 minutes, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose. | AUClast is the AUC from the time of dosing to the last measurable concentration of the drug. |
| Pooled Urine PK (fe) of Zilebesiran and Its Metabolite | Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose. | — |
Countries
Japan
Contacts
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Participant flow
Recruitment details
Participants with mild to moderate hypertension were enrolled at three (3) sites in Japan.
Baseline characteristics
| Characteristic | — |
|---|---|
| 24-hour Mean Blood Pressure by Ambulatory Blood Pressure Monitoring (ABPM) Baseline Diastolic Blood Pressure (DBP; Actual) | 85.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 5.4 |
| 24-hour Mean Blood Pressure by Ambulatory Blood Pressure Monitoring (ABPM) Baseline Systolic Blood Pressure (SBP; Actual) | 138.9 millimeters of mercury (mmHg) STANDARD_DEVIATION 8 |
| Age, Categorical Age category (years), n (%) <=18 years | 0 Participants |
| Age, Categorical Age category (years), n (%) >=65 years | 6 Participants |
| Age, Categorical Age category (years), n (%) Between 18 and 65 years | 30 Participants |
| Age, Continuous | 58 Years |
| Mean Office Blood Pressure (OBP) Baseline DBP (Actual) | 89.2 mmHg STANDARD_DEVIATION 6.3 |
| Mean Office Blood Pressure (OBP) Baseline SBP (Actual) | 136 mmHg STANDARD_DEVIATION 10 |
| Race (NIH/OMB) Race, n (%) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Race, n (%) Asian | 36 Participants |
| Race (NIH/OMB) Race, n (%) Black or African American | 0 Participants |
| Race (NIH/OMB) Race, n (%) More than one race | 0 Participants |
| Race (NIH/OMB) Race, n (%) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Race, n (%) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Race, n (%) White | 0 Participants |
| Sex: Female, Male Sex (male or female), n (%) Female | 6 Participants |
| Sex: Female, Male Sex (male or female), n (%) Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 6 / 12 | 6 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
None listed