A Study to Evaluate ALN-AGT01 in Patients With Hypertension
Phase 1
Completed
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT03934307
- Lead Sponsor
- Alnylam Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: SAD: ALN-AGT01-Matching Placebo ALN-AGT01-Matching Placebo Participants will be administered a single dose of ALN-AGT01-matching placebo. Part B: SD: ALN-AGT01 ALN-AGT01 Participants with controlled salt intake will be administered a single dose of ALN-AGT01. Part A: SAD: ALN-AGT01 ALN-AGT01 Participants will be administered a single dose of ALN-AGT01. Part B: SD: ALN-AGT01-Matching Placebo ALN-AGT01-Matching Placebo Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo Irbesartan-Matching Placebo Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan ALN-AGT01-Matching Placebo Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. Part E: Open Label: ALN-AGT01 + Irbesartan ALN-AGT01 Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo ALN-AGT01 Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan Irbesartan Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. Part E: Open Label: ALN-AGT01 + Irbesartan Irbesartan Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧Manchester, United Kingdom