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

PHASE1RECRUITING

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

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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)
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2024-03-21

    Primary completion: 2025-12-31

    Study completion finish: 2026-06-30

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

    trial

    Trial ID

    NCT06205628

    Intervention or treatment

    DRUG: ADX-850

    DRUG: Placebo

    DRUG: Angiotensin Receptor Blockers

    Conditions

    • Hypertension
    • Hypertension,Essential

    Find a site

    Closest Location:

    CMAX Clinical Research

    Research sites nearby

    Select from list below to view details:

    • CMAX Clinical Research

      Adelaide, South Australia, Australia

    • Linear Clinical Research

      Nedlands, Western Australia, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: PART 1 - Active ADX-850 administered to patients with hypertension
    • For Cohort 1 in Part 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-850) : 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.
    • For Cohort 2, the option either to enroll 8 or expand to 16 patients in a 3:1 ratio will be made following review of Cohort 1. For Cohorts 3 and 4, 16 patients will be randomized in a 3:1 ratio; 12 patients to active (ADX-850) : 4 patients to control (matched placebo).
    DRUG: ADX-850
    • siRNA duplex oligonucleotide
    PLACEBO_COMPARATOR: PART 1 - Placebo administered to patients with hypertension
    • For Cohort 1 in Part 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-850) : 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.
    • For Cohort 2, the option either to enroll 8 or expand to 16 patients in a 3:1 ratio will be made following review of Cohort 1. For Cohorts 3 and 4, 16 patients will be randomized in a 3:1 ratio; 12 patients to active (ADX-850) : 4 patients to control (matched placebo).
    DRUG: Placebo
    • Saline
    EXPERIMENTAL: PART 2 - Active ADX-850 administered to patients with hypertension
    • This will be initiated at the dose level determined by the Safety Review Committee from SAD in Part 1. The treatment of hypertension patients is an open-label study.
    DRUG: ADX-850
    • siRNA duplex oligonucleotide
    EXPERIMENTAL: PART 2 - Active ADX-850 plus ARB therapy administered to patients with hypertension
    • Following ADX-850 dosing in Part 2, patients with remaining elevated blood pressure will additionally receive regular dosing of an angiotensin receptor blocker as an as-indicated concomitant therapy.
    DRUG: ADX-850
    • siRNA duplex oligonucleotide

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    PART 1 - Safety in Patients with HypertensionTo evaluate the safety and tolerability of ADX-850 in hypertension patients by incidence, relationship, and severity of adverse events and serious adverse events365 days
    PART 2 - Safety in Patients with HypertensionTo 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 events365 days

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the Maximum Observed Concentration (Cmax) based on concentration in plasma8 days
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the Dose-Normalized Maximum Observed Concentration (Cmax/D) based on concentration in plasma8 days
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the Time to Maximum Observed Concentration (Tmax) based on concentration in plasma8 days
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the Area Under the Concentration-Time Curve (AUC) based on concentration in plasma8 days
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the Dose-Normalized Area Under the Concentration-Time Curve (AUC/D) based on concentration in plasma8 days
    PART 1 - Plasma Pharmacokinetics in Patients with HypertensionTo characterize the Pharmacokinetics of ADX-850 by measuring the terminal half-life (t½) based on concentration in plasma8 days
    PART 1 - Biomarker Activity in Patients with HypertensionTo characterize the change from baseline in plasma AGT concentration365 days
    PART 2 - Biomarker Activity in Patients with HypertensionTo characterize the change from baseline in plasma AGT concentration365 days

    Frequently Asked Questions

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    References

    Clinical Trials Gov: Safety, Tolerability, PK and PD of ADX-850 in Participants With Hypertension

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