Clinical trial NCT06205628: Safety, Tolerability, PK and PD of ADX-850 in Participants With Hypertension
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ADX-850 in Participants With Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hypertension
Hypertension,Essential
Keywords: Hypertension
Lead sponsor: ADARx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ADARx Australia Pty Ltd
name: Avance Clinical Pty Ltd.
First posted: 2024-01-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Model Description
Primary purpose: TREATMENT

Brief 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.

Detailed 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, blinded, placebo-controlled, parallel group, single ascending dose (SAD) in participants with hypertension with up to 7 dose cohorts.
* Open-label, parallel group, single fixed dose of ADX-850 in participants with hypertension. After ADX-850 dosing, participants with elevated blood pressure will additionally receive regular dosing of an ARB as an as-indicated concomitant therapy.

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) between 18 and 35 kg/m2
* Documentation of mild to moderate hypertension, mean of \>130 and \<165mmHg
* 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)
* Negative urine drug and breath alcohol test
* Must be a non-smoker for the duration of the study

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
* Blood donation within 30 days prior to study drug administration
* Night shift workers (regular working hours between 10:00 PM and 6:00 AM)
* Known history of intolerance to ARB medication (Part 2 only)

Primary outcomes:
measure: PART 1 - Safety in Participants with Hypertension
timeFrame: 365 days
measure: PART 2 - Safety in Participants with Hypertension
timeFrame: 365 days
Secondary outcomes:
measure: PART 1 - Pharmacokinetics in Participants with Hypertension
timeFrame: 8 days
measure: PART 1 - Biomarker activity in Participants with Hypertension
timeFrame: 365 days
measure: PART 2 - Biomarker Activity in Participants with Hypertension on a stable dose of ARB
timeFrame: 365 days
Other outcomes:
measure: PART 1 - Pharmodynamics in Participants with Hypertension
timeFrame: 365 days
measure: PART 1 - Rescue Medication use in Participants with Hypertension
timeFrame: 365 days
measure: Part 1 - Immunogenicity in Participants with Hypertension
timeFrame: 365 days
measure: Part 2 - Pharmodynamics in Participants with Hypertension
timeFrame: 365 days
measure: PART 2 - Biomarker activity in Participants with Hypertension
timeFrame: 365 days
measure: PART 2 - Rescue Medication in Participants with Hypertension
timeFrame: 365 days
measure: Part 2 - Immunogenicity in Participants with Hypertension
timeFrame: 365 days
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Perth
country: Australia
facility: Clinitrials Pty Ltd
Study officials:
References: