Safety, Tolerability, PK and PD of ADX-850 in Participants With Hypertension

Hypertension Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ADX-850 in Participants With Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06205628
• Other study ID #: ADX-850-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 21, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: April 2024
• Source: ADARx Pharmaceuticals, Inc.
• Contact: Markus P Schlaich, MD
• Phone: +61892240382
• Email: markus.schlaich[@]uwa.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The first-in-human Phase 1 study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ADX-850 in patients with hypertension.

Description:

The clinical study described in this protocol is a Phase 1, two-part, multi-center study evaluating safety, tolerability, PK, and PD of ADX-850.

The study consists of two parts:

• Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in patients with hypertension with up to 4 dose cohorts. For SAD cohorts and planned dosing; and

• Open-label, parallel group, single fixed dose of ADX-850 in patients with hypertension. After ADX-850 dosing, patients with elevated blood pressure will additionally receive regular dosing of an ARB as an as-indicated concomitant therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) between 18 and 35 kg/m2

• Body weight =55 kg

• No use of antihypertensive medication for a minimum of 2 weeks or 5 half-lives

• Access to and ability to use antihypertensive medication/access to emergency services to treat hyper- or hypotensive events

• Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

• Willing and able to provide informed consent and comply with all study visits

• Willing to start or switch to irbesartan as concomitant ARB therapy, if applicable (Part 2 only)

Exclusion Criteria:

• Any significant medical history

• Secondary hypertension

• Active malignancy and/or history of malignancy in the past 5 years

• History of liver disease, Gilbert's syndrome, nonalcoholic steatohepatitis, severe steatosis, or abnormal liver function test

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, red blood cell (RBC), hemoglobin, hematocrit, reticulocytes, gamma-glutamyl transferase (GGT), and creatinine must be within normal range at screening and prior to dosing

• Any active infection or acute illness

• Major surgery or significant traumatic injury occurring within 3 months

• Any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study

• Mean sitting diastolic BP (DBP) =110 mmHg at any time prior to randomization.

• Orthostatic hypotension

• eGFR <60 mL/min/1.73m2

• Abnormal potassium levels <3.5 and >5 mmol/L

• History or presence of clinically significant ECG abnormalities and corrected QTcF >450 ms prior to dosing

• Positive serology tests (HepB, Hep C, HIV)

• Use of unapproved prescription, vaccines, supplements/vitamins, or over-the counter medication

• Treatment with another investigational product concurrently or within 30 days prior to the first study drug administration

• Known hypersensitivity to any of the study drug ingredients

• Pregnancy, intent to become pregnant during the course of the study, or lactating women

• History or presence of alcohol abuse

• Night shift workers (regular working hours between 10:00 PM and 6:00 AM)

• Known history of intolerance to ARB medication (Part 2 only)

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension
• Hypertension,Essential

Intervention

Drug:
• ADX-850
siRNA duplex oligonucleotide
• Placebo
Saline
• Angiotensin Receptor Blockers
Angiotensin receptor blocker

Locations

Country	Name	City	State
Australia	CMAX Clinical Research	Adelaide	South Australia
Australia	Linear Clinical Research	Nedlands	Western Australia

Sponsors (2)

Lead Sponsor	Collaborator
ADARx Pharmaceuticals, Inc.	ADARx Australia Pty Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PART 1 - Safety in Patients with Hypertension	To evaluate the safety and tolerability of ADX-850 in hypertension patients by incidence, relationship, and severity of adverse events and serious adverse events	365 days
Primary	PART 2 - Safety in Patients with Hypertension	To evaluate the safety and tolerability of ADX-850 in hypertension patients by incidence, relationship, and severity of adverse events, adverse events of special interest, and serious adverse events	365 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the Maximum Observed Concentration (Cmax) based on concentration in plasma	8 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the Dose-Normalized Maximum Observed Concentration (Cmax/D) based on concentration in plasma	8 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the Time to Maximum Observed Concentration (Tmax) based on concentration in plasma	8 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the Area Under the Concentration-Time Curve (AUC) based on concentration in plasma	8 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the Dose-Normalized Area Under the Concentration-Time Curve (AUC/D) based on concentration in plasma	8 days
Secondary	PART 1 - Plasma Pharmacokinetics in Patients with Hypertension	To characterize the Pharmacokinetics of ADX-850 by measuring the terminal half-life (t½) based on concentration in plasma	8 days
Secondary	PART 1 - Biomarker Activity in Patients with Hypertension	To characterize the change from baseline in plasma AGT concentration	365 days
Secondary	PART 2 - Biomarker Activity in Patients with Hypertension	To characterize the change from baseline in plasma AGT concentration	365 days