Summary of reported treatment-emergent AEs by treatment groups in Study 1 (Safety analysis set).
deaths, neutropenia, diarrhea, respiratory failure, vomiting, anemia, vomiting and diaper dermatitis, RSV bronchiolitis, respiratory syncytial virus, Neutropenia, hypokalemia
LYMPHADENITIS, FLUID OVERLOAD, NEUTROPENIA, FEBRILE NEUTROPENIA, RESPIRATORY FAILURE, HYPOMAGNESEMIA, ANEMIA, BACTERIAL PNEUMONIA, ADVERSE EVENT, DIAPER DERMATITIS, EVENTS, NEUTROPENIA
AE, adverse event; ALT, alanine aminotransferase increased; AST, aspartate aminotransferase increased; CPK, creatinine phosphokinase; LRT, lower respiratory tract; MAD, multiple-ascending dose; RSV, respiratory syncytial virus; SAD, single-ascending dose; URT, upper respiratory tract.In the MAD phase, diarrhea was the most frequently reported AE in 16 (11 [14.1%] patients in lumicitabine, 5 [15.0%] in placebo) patients, followed by vomiting and diaper dermatitis in 13 patients each (vomiting: 12 [15.4%] patients in lumicitabine; 1 [3.0%] patient in placebo; diaper dermatitis: 9 [11.5%] patients in lumicitabine and 4 [12.1%] patients in placebo). Increased aspartate aminotransferase was reported in 10 patients (9 [11.5%] patients in lumicitabine and 1 [3.0%] patient in placebo). None of the AEs led to drug interruptions. Regarding clinical laboratory evaluations reported as AEs, there were slight (all maximum Grade 1 or 2) dose-related transient (return to baseline by day 11) increases in alanine aminotransferase (6 [7.7%] in overall lumicitabine, and none in placebo) and aspartate aminotransferase (9 [11.5%] in overall lumicitabine, and 1 [3.0%] in placebo). However, there was no change in bilirubin in any group. Most of these increases were considered at least possibly related to treatment. Neutropenia was reported as an AE in 7 patients (3 [16.7%] in the lumicitabine 40/20 mg/kg group, 3 [18.8%] in the lumicitabine 60/40 mg/kg group and 1 [3.0%] in placebo), and was considered at least possibly related to the study drug in 3 of these patients (2 [11.1%] in the 40/20 mg/kg group and 1 [6.3%] in the 60/40 mg/kg group). Two (11.1%) patients in the 40/20 mg/kg LD/MD group experienced an AE that led to the study drug discontinuation: One patient experienced hypokalemia, hypomagnesemia, bacterial pneumonia, respiratory failure, and fluid overload; the other patient experienced neutropenia. AEs in both patients resolved after drug discontinuation. Grade 3 events reported were respiratory failure in two patients in 40/20 mg/kg group and anemia in one patient in the 30/10 mg/kg group. There were no trends in the vital sign values.Serious treatment-emergent AEs were reported in 3 patients in the lumicitabine groups (respiratory failure and RSV bronchiolitis, considered not related to the study drug; neutropenia, considered possibly related to the study drug) and in 1 patient in the placebo group (lymphadenitis not related to the study drug).All 7 patients treated in Study 2 experienced at least one AE, majority being Grade 1 or 2 in severity. There were no AEs leading to permanent withdrawal of the study treatment. Grade 3 neutropenia was followed by a Grade 3 febrile neutropenia; both were reported in one patient in the 60/40 mg/kg LD/MD lumicitabine group. Additionally, Grade 2 neutropenia was reported in 1 patient in the same treatment group. These neutropenia events were considered at least possibly related to lumicitabine by the investigator. No deaths were reported during the studies.In both studies, a transient decrease in the absolute neutrophil count in the lumicitabine groups was observed, with higher grade neutropenia being observed with increased doses and exposures (