Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 (zilebesiran) in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.
Interventions
DRUGALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
DRUGALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
DRUGIrbesartan
Irbesartan will be administered orally.
DRUGIrbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of \>130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and \>135 and ≤165 mmHg without hypertensive medication for Part E * Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m\^2; Part D: Has BMI \>35 and ≤50 kg/m\^2; Part E: Has BMI ≥18 kg/m\^2 and ≤50 kg/m\^2 * Has a normal 12-lead electrocardiogram (ECG) * Is a nonsmoker
Exclusion criteria
* Has secondary hypertension * Has orthostatic hypotension * Has estimated glomerular filtration rate (eGFR) of \<60 mL/min/1.73m\^2 * Recently received an investigational agent * Has diabetes mellitus * Has history of any cardiovascular event * Has history of intolerance to SC injection(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Adverse Events (AEs) | Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Blood Angiotensinogen (AGT) Level | Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months |
| Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites | Parts A, B and E: Up to Day 15; Part D: Up to Day 99 |
| Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites | Parts A, B and E: Up to Day 15; Part D: Up to Day 99 |
Countries
United Kingdom
Outcome results
None listed