Safety and Tolerability
death, bleeding, overdose, pelvic pain, fracture, cirrhosis, fibrosis, hematuria, dizziness, kidney pain, intentional self-injury, pollakiuria, deaths
CHOLESTASIS AND JAUNDICE, BLEEDING, ADVERSE EVENTS, EVENT, CIRRHOSIS, EVENTS, HEPATIC FAILURE, FIBROSIS, HEMATURIA, NONINFECTIOUS HEPATITIS, ADVERSE EVENT, VIRAL PERICARDITIS, PETIT MAL EPILEPSY, HYPERTENSIVE CRISIS
Treatment-emergent AEs were reported for 44 of 48 participants (92%) in the tolvaptan group and 42 of 43 participants (98%) in the placebo group during phase A of the trial. The most frequent AEs are shown in Table Summary of adverse events and listing of individual treatment-emergent adverse events (by system organ class and MedDRA preferred term) occurring in ≥5% of participants in either treatment groupAE, adverse event.Defined as an AE that started after the initiation of study medication; or if the event was continuous from baseline and was serious, study medication-related, or resulted in death, discontinuation, interruption, or reduction of study medication. Multiple occurrences of treatment-emergent AEs are counted once per MedDRA preferred term.This participant discontinued trial medication but continued participating in the trial (Data on urine volume in the 24 hours after dosing were collected for a subset of tolvaptan (In the nine tolvaptan-treated participants who experienced increased creatinine, the event resolved in all patients, with no action taken regarding tolvaptan in six participants, tolvaptan interruption in two participants, and tolvaptan dose reduction in one participant. Potentially clinically significant increases in creatinine occurred in four participants in the tolvaptan group and no participant in the placebo group during phase A.For five hepatic standardized MedDRA queries (cholestasis and jaundice of hepatic origin; hepatic failure, fibrosis and cirrhosis, and other liver damage-related conditions; noninfectious hepatitis; liver-related investigations, signs, and symptoms; and liver-related coagulation and bleeding disturbances),One participant in the tolvaptan group had a serious treatment-emergent AE (viral pericarditis). Six participants in the placebo group had serious treatment-emergent AEs: one had a hand fracture and ulna fracture, one had hematuria and kidney pain, one had an intentional overdose and intentional self-injury, and one participant each had petit mal epilepsy, hypertensive crisis, and pelvic pain. None of the serious treatment-emergent AEs reported in either treatment group were assessed by the investigator as related to the study drug. There were no deaths. One participant in the tolvaptan group and two participants in the placebo group had treatment-emergent AEs that were assessed as severe (Two participants discontinued treatment because of AEs: one in the tolvaptan group (because of pollakiuria) and one in the placebo group (because of dizziness). Both events were assessed as of moderate severity and related to the study drug.Mean changes from baseline in height SD scores were similar between the tolvaptan and placebo arms across age and sex subgroups (The PedsQL Generic Core Scale and the PedsQL Multidimensional Fatigue Scale showed that quality of life was unchanged from baseline to month 12 (