TALEN is a prospective randomised double-blind placebo-controlled phase 2 study of 5-Aminolevulinic Acid with Sodium Ferrous Citrate (5-ALA-SFC) in adult patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). TALEN aims to identify the optimal biological dose (OBD) of 5-ALA-SFC.

TALEN is a prospective, randomised, double blind, placebo-controlled phase 2 study of 5-ALA-SFC administration in adults undergoing non-emergent cardiac surgery on CPB examining the potential of 5-ALA-SFC to induce haem oxygenase-1 (HO-1) as a novel cardio- and cyto-protective strategy for clinical benefit. 5-ALA is an amino acid found in several foods and a natural endogenous precursor in the synthesis of haem. Oral administration of 5-ALA-SFC has been shown to be safe and to induce a pharmacodynamic effect on the key effector, HO-1. TALEN is designed as a dose-finding trial with sequential dose cohorts, evaluating the safety, tolerability and PD response to 5-ALA-SFC to determine the optimum biological dose for further evaluation.

Inclusion Criteria:

• Scheduled for non-emergent cardiac surgery under CPB (including coronary artery bypass grafting, valve replacement, valve repair or a combination thereof)
• Signed informed consent
• Age ≥18 years
• Able and willing to comply with all study requirements

Exclusion Criteria:

• Female participants who are of childbearing potential who are either unable or unwilling to use highly effective contraception, or who are pregnant or breast feeding
• History of hypersensitivity to 5-ALA, SFC and/or porphyrins
• Acute or chronic types of porphyria
• Known genetic haemochromatosis or clinically significant iron overload
• History of clinically significant photosensitization
• Current long-term (> 3 months) use of amiodarone
• Concomitant use of hypericin extract (including St John's Wort) or concomitant therapeutic dose oral iron replacement
• Use of other investigational medical product(s) < 28 days prior to study or 5 half-lives, whichever is longer
• Cardiogenic shock/Low cardiac output syndrome requiring catecholamine infusion and/or mechanical circulatory support prior to induction of anaesthesia for cardiac surgery
• Recent acute myocardial infarction
• Cardiac surgery without cardiopulmonary bypass or induced fibrillating heart surgery
• Inadequate renal or liver function
• Any other condition which, in the opinion of the Investigator, makes the patient unsuitable for or may compromise their participation in the study

Randomisation will follow a sequential randomisation list prepared by the blinded trial statistician. As participants are randomised, they will be manually allocated the next available treatment kit (active or placebo) number from this list which will correspond to the randomisation number.