Safety and tolerability
malaria, vomiting, headache, hepato-biliary disorders
ADVERSE EVENTS, ADVERSE EVENT, MALARIA
Treatment emergent adverse events of any cause were reported in 51.4% (18/35) of patients in the ferroquine only group, and in the combination arms for 58.3% (21/36) with 300 mg, 66.7% (24/36) with 600 mg, and 72.7% (24/33) with 1000 mg artefenomel. The most common adverse events were malaria (20.0%; 7/35) with ferroquine alone, malaria and headache (both 16.7%; 6/36) with artefenomel 300 mg, malaria (22.2%; 8/36) with artefenomel 600 mg, and vomiting (30.3%; 10/33) with 1000 mg artefenomel (Fig. Most common treatment emergent adverse events of any cause. Safety population. Data are % patients for adverse events occurring in > 3% of patients in any treatment group. AE, adverse eventAll adverse events were of mild-to-moderate severity (Fig. Adverse events considered in the investigator’s opinion related to drug administration occurred in 7.9% (11/140) of patients with ferroquine, most commonly vomiting (3.6%; 5/140) (Additional file There was one case of ALT increased in the ferroquine/artefenomel 1000 mg arm (3.0%; 1/33) observed in a female patient with baseline elevations of ALT (1.1xULN), alkaline phosphatase (ALP) (3.2xULN), and total bilirubin (1.2xULN), and no history of hepato-biliary disorders. From Day 5, ALT increased to a maximum of 3.3xULN on Day 15, with concurrent ALP 5.4xULN, AST 1.3xULN, and total bilirubin 1.2xULN. Total bilirubin continued to rise, peaking at 3.4xULN on Day 25 with direct bilirubin at 4.7xULN and ALP at 5xULN. There were no symptoms, and ALT, AST, and total bilirubin values had returned to normal by Day 42 without intervention. Further elevations in ALT (1.7xULN), AST (1.5xULN), total bilirubin (1.3xULN), and ALP (2.6xULN) were noted on Day 96, but all measures had resolved to baseline levels by Day 141.There was no difference in the maximum post-baseline change in haematology parameters between treatment groups, which were consistent with recovery from malaria (Additional file There were no differences between treatment arms in vital signs (Additional file 