Safety, Tolerability, PK and PD of ADX-850 in Participants with Hypertension
Phase 1
Recruiting
- Conditions
- Hypertension,EssentialHypertension
- Interventions
- Registration Number
- NCT06205628
- Lead Sponsor
- ADARx Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PART 2 - Active ADX-850 plus ARB therapy administered to participants with hypertension ADX-850 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. PART 1 - Active ADX-850 administered to participants with hypertension ADX-850 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. PART 1 - Placebo administered to participants with hypertension Placebo 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. PART 2 - Active ADX-850 administered to participants with hypertension ADX-850 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. PART 2 - Active ADX-850 plus ARB therapy administered to participants with hypertension Angiotensin Receptor Blockers 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.
- Primary Outcome Measures
Name Time Method PART 1 - Safety in Participants with Hypertension 365 days To evaluate the safety and tolerability of ADX-850 in hypertension patients by incidence, and severity of adverse events and serious adverse events
PART 2 - Safety in Participants with Hypertension 365 days To evaluate the safety and tolerability of ADX-850 in hypertension patients by incidence, nature, and severity of adverse events, adverse events of special interest, and serious adverse events
- Secondary Outcome Measures
Name Time Method PART 1 - Pharmacokinetics in Participants with Hypertension 8 days To characterize the Pharmacokinetics of ADX-850 by measuring the Maximum Observed Concentration (Cmax) based on concentration in plasma
PART 1 - Biomarker activity in Participants with Hypertension 365 days Change from baseline in plasma concentration over time
PART 2 - Biomarker Activity in Participants with Hypertension on a stable dose of ARB 365 days To characterize the change from baseline in plasma concentration over time
Trial Locations
- Locations (2)
CMAX Clinical Research
🇦🇺Adelaide, South Australia, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia