A Phase 1/2, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics, and Pharmacokinetics of Zilebesiran in Japanese Patients With Mild to Moderate Hypertension

Alnylam Pharmaceuticals3 sites in 1 country36 target enrollmentJune 5, 2024

ConditionsMild to Moderate Hypertension

InterventionsPlacebo Zilebesiran

DrugsZilebesiran Placebo

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Mild to Moderate Hypertension
Sponsor: Alnylam Pharmaceuticals
Enrollment: 36
Locations: 3
Primary Endpoint: Frequency of Adverse Events (AEs)
Status: Completed
Last Updated: 2 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 5, 2024

End Date

July 17, 2025

Last Updated

2 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alnylam Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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)

Arms & Interventions

Placebo

Participants will be administered a single dose of placebo.

Intervention: Placebo

Zilebesiran

Participants will be administered a single dose of zilebesiran.

Intervention: Zilebesiran

Outcomes

Primary Outcomes

Frequency of Adverse Events (AEs)

Time Frame: Up to 12 months

Number of Participants With Adverse Events (AEs)

Time Frame: 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 Outcomes

Change from Baseline at Month 3 and Month 6 in SBP and DBP Assessed by Office Blood Pressure(Baseline and Month 3 and Month 6)
Percent Change from Baseline in Serum Angiotensinogen (AGT) at Month 3 and Month 6(Baseline and Month 3 and Month 6)
Pharmacokinetics of Zilebesiran and its Metabolite assessed by Plasma Concentration(Predose and up to 3 days postdose)
Change from Baseline at Month 3 and Month 6 in 24-hour Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Assessed by Ambulatory Blood Pressure Monitoring (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)
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)
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.)
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.)
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.)
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.)
Pooled Urine PK (fe) of Zilebesiran and Its Metabolite(Predose and 2 to 6, 6 to 12, and 12 to24 hours post-dose.)