Clinical trial NCT06639087: A Phase Ib Study of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment
Official title: Phase Ib Randomised, Placebo-controlled, Double-blind, Multicentre Study to Assess the Effects and Safety of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Heart Failure
Keywords: Relaxin family peptide receptor 1 agonist
Estimated glomerular filtration rate
Heart failure
Renal impairment
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2024-10-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to investigate the effects and safety of AZD5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment.

Detailed description: This is a randomized, double-blind, placebo-controlled Phase 1b study to evaluate the safety, pharmacodynamics, and pharmacokinetics of AZD5462 on top of dapagliflozin in participants with heart failure and renal impairment.

The study will include 5 periods and approximately 9 study site visits:

* Screening Period of up to 4 weeks (at least one study visit)
* Run-in Period of up to 4 weeks (one study visit)
* Inpatient Treatment Period of 4 days (one study visit)
* Outpatient Treatment Period of up to 4 weeks (three study visits)
* Follow-up Period of up to 4 weeks (three study visits)

Eligibility criteria: Inclusion Criteria:

* Participants must have a pre-existing diagnosis of heart failure (HF).
* Participants must have a left ventricular ejection fraction (LVEF) of ≤ 40% based on echocardiography taken within the last 9 months.
* Participants must have an estimated glomerular filtration rate (eGFR) of 30 to 60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m2) (inclusive) at Screening as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 (creatinine) equation.
* Participants must be on stable HF standard of care (SoC) medication for at least 4 weeks prior to Screening. If the participant is currently taking diuretics, then diuretics must also be stable for at least one week prior to Screening.
* Participants must be on stable Sodium-glucose co-transporter-2 inhibitors (SGLT2) inhibitor treatment for at least 12 weeks prior to Screening.
* Minimum BMI of 18 kilograms per meter squared (kg/m2) at Screening.

Exclusion Criteria:

* Historical or current evidence of a clinically significant disease or disorder.
* Participants with a known hypersensitivity to AZD5462 or dapagliflozin, or to any of the excipients of these drug products.
* Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication.
* Cardiac ventricular arrhythmia that requires treatment. However, participants with atrial fibrillation or flutter and controlled ventricular rate (eg, resting heart rate \< 110 beats per minute) are permitted. Participants with cardiac ventricular arrhythmia that are treated with antiarrhythmic agents (eg, amiodarone) and are stable are permitted.
* History of or anticipated heart transplant.
* Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, valve repair/replacement, aortic aneurysm surgery).
* Any evidence of clinically important disease or disorder which in the Investigator's opinion makes it undesirable for the participant to participate in the study.
* Positive hepatitis C antibody, hepatitis B virus surface antigen, or hepatitis B virus core antibody at Screening.

Primary outcomes:
measure: Change in sodium excretion
timeFrame: From Baseline to Day 1
Secondary outcomes:
measure: Change in urine albumin-creatinine ratio (uACR)
timeFrame: From Baseline to Day 1 and 29
measure: Change in haematocrit
timeFrame: From Baseline to Day 29
measure: Number of adverse events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline to Day 57
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Research Site
Study officials:
References: