Clinical trial NCT03934307: A Study to Evaluate ALN-AGT01 in Patients With Hypertension
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-05-01
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
Secondary outcomes:
measure: Change from Baseline in Blood Angiotensinogen (AGT) Level
timeFrame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
measure: Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites
timeFrame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
measure: Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites
timeFrame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Manchester
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: