AZD5462 / AstraZeneca - LARVOL DELTA

AURORA: A Phase Ib Study of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=40 ➔ 8

Enrollment change • Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry for the Determination and Identification of AZD5462 and Its Metabolites in Rat Plasma. (PubMed, Biomed Chromatogr) - "The metabolic pathways of AZD5462 include oxygenation and glucuronidation. This study is the first report on the pharmacokinetics and metabolism of AZD5462, which would provide insights into the effectiveness and toxicity of this drug candidate."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure

GLITTER: A Study to Investigate the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | N=25 ➔ 16 | Trial completion date: Apr 2025 ➔ Dec 2024 | Trial primary completion date: Apr 2025 ➔ Dec 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Renal Disease

GLITTER: A Study to Investigate the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

GLITTER: A Study to Investigate the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Renal Disease

AURORA: A Phase Ib Study of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

LUMINARA: A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans (ERA-EDTA 2024) - "Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients."

Cardiovascular • Congestive Heart Failure • Heart Failure

Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. (PubMed, J Med Chem) - "AZD5462 was well tolerated in both rat and cynomolgus monkey and has successfully completed phase I studies in healthy volunteers. In summary, AZD5462 is a small molecule pharmacological mimetic of relaxin H2 signaling at RXFP1 and holds promise as a potential therapeutic approach to treat heart failure patients."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

LUMINARA: A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure (clinicaltrials.gov) - P2 | N=360 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

Safety, tolerability, and pharmacokinetics of AZD5462, a small molecule agonist of the RXFP1 relaxin receptor (ESC 2023) - "Introduction: Despite multiple new drug advancements for patients with heart failure in recent years (specifically, sodium-glucose co-transporter-2 and sacubitril/valsartan), morbidity and mortality remain high. AZD5462 was generally well tolerated at all dose levels in this phase 1 study. These data pave the way for development of a chronic oral relaxin therapy for patients with heart failure."

Clinical • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Ventricular Tachycardia

Pharmacokinetics of AZD5462 in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

Pharmacokinetics of AZD5462 in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=16 ➔ 8

Enrollment change • Enrollment closed

A Study to Assess the Effect of Multiple Doses of AZD5462 on the Pharmacokinetics (PK) of Drugs in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD5462 Following Single and Multiple Ascending Dose Administration to Healthy Volunteers (clinicaltrials.gov) - P1 | N=98 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

Pharmacokinetics of AZD5462 in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

Pharmacokinetics of AZD5462 in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A Study to Assess the Effect of Multiple Doses of AZD5462 on the Pharmacokinetics (PK) of Drugs in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Effect of Multiple Doses of AZD5462 on the Pharmacokinetics (PK) of Drugs in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial