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

ADARx Pharmaceuticals

Status and phase

Enrolling

Phase 1

Conditions

Hypertension,Essential

Hypertension

Treatments

Drug: Placebo

Drug: Angiotensin Receptor Blockers

Drug: ADX-850

Study type

Interventional

Funder types

Industry

Other

Identifiers

NCT06205628

ADX-850-101

Details and patient eligibility

About

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

Full 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.

Enrollment

120 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Quadruple Blind

120 participants in 4 patient groups, including a placebo group

PART 1 - Active ADX-850 administered to participants with hypertension

Experimental group

Description:

Part 1 includes up to 7 sequential dose cohorts (4 planned and 3 optional) to evaluate doses ranging from 100 to 800 mg (Table 3). In each cohort, 8 participants will be randomized in a 3:1 ratio to ADX-850 or placebo with the option to increase enrollment to 16 participants at the Sponsor's discretion and with SRC agreement. At the start of each cohort, 2 sentinel participants (1 ADX-850 and 1 placebo) will be treated. The Medical Monitor and Investigator will review the available safety data from the first 48 hours after dosing to ensure safety before continuing enrollment in that cohort.

Treatment:

Drug: ADX-850

PART 1 - Placebo administered to participants with hypertension

Placebo Comparator group

Description:

Treatment:

Drug: Placebo

PART 2 - Active ADX-850 administered to participants with hypertension

Experimental group

Description:

In Part 2, participants with hypertension will be dosed with ADX-850 in an open-label, parallel arm fashion. Participants whose SBP \>120 mmHg at Day 57 will be administered irbesartan, 150 to 300 mg, once daily. Dosing of the combination treatment group will begin with 2 sentinel participants who will be followed for safety for 48 hours after starting their irbesartan regimen before the decision is made by the Investigator and Medical Monitor to continue with combination treatment for all other participants who meet the criteria for irbesartan administration.

Treatment:

Drug: ADX-850

PART 2 - Active ADX-850 plus ARB therapy administered to participants with hypertension

Experimental group

Description:

Treatment:

Drug: ADX-850

Drug: Angiotensin Receptor Blockers