Acute Ischemic Stroke (AIS) MedDRA version: 20.0 Level: LLT Classification code 10008107 Term: Cerebral edema System Organ Class: 100000004852
Conditions
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Participants who are between the ages >=18 and 15 for the non-dominant hemisphere and > 20 for the dominant hemisphere ? Participants who present with a wake-up stroke (WUS) who are =65 years) yes F.1.3.1 Number of subjects for this age range 59
Exclusion criteria
Exclusion criteria: ? Participants who are >12 hours from LKW at the start of treatment with study drug or >8 hours from awakening with WUS ? Any MLS on brain imaging ? Evidence of parenchymatous hematoma ([PH]1 or PH2) on baseline imaging (per Heidelberg classification) ? Evidence of additional anterior cerebral artery (ACA) infarction ? Diagnosis of brain death ? Planned surgical decompression prior to randomization ? Participants with a known history of a hereditary bleeding disorder which increases bleeding risk ? Chronic kidney disease stage III or higher ? Hepatic injury ? Diagnosis of diabetes insipidus ? Participants who have received any prophylactic hyperosmolar therapy ? Participants who have received treatment with any other V1a and/or V2 receptor-blocking agent or glyburide ? A preexisting medical condition for which the participant is unlikely to survive the next 6 months ? Planned limitation or withdrawal of life-sustaining treatment during hospital admission ? Participants who are pregnant or breastfeeding, or intending to become pregnant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To evaluate the efficacy of balovaptan compared with placebo based on the amount of midline shift (MLS);Secondary Objective: ? To evaluate the efficacy of balovaptan compared with placebo based on global disability, amount of MLS, proportion of patients with surgical decompressive hemicraniectomy (DHC), proportion of patients who received hyperosmolar therapy, impairment of consciousness, neurological impairment, mortality, functional independence, stroke disability and health-related quality of life, hospital length of stay and ICU length of stay ? To evaluate the safety of balovaptan compared with placebo ? To characterize the balovaptan, M2, and M3 pharmacokinetic (PK) profile ;Primary end point(s): 1. Amount of MLS, as measured in millimeters at the level of the septum pellucidum on NCCT at 72 hours from LKW;Timepoint(s) of evaluation of this end point: 1. At 72 hours from LKW | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Global disability, defined as the proportion of participants with modified Rankin Scale-Structured Interview (mRS-SI) score 4 measured at Day 90 2. Amount of MLS, as measured in millimeters at the level of the septum pellucidum on non-contrast computed tomography (NCCT) at 48 hours and 96-120 hours from LKW 3. Proportion of patients with surgical DHC performed 4. Proportion of patients who received hyperosmolar therapy following initiation of study treatment 5. Impairment of consciousness, as measured by the Glasgow Coma Scale (GCS) score up to Day 4 6. Neurological impairment, as measured by the NIHSS on hospital Day 4 and Day 90 7. Mortality at Day 30 8. Global disability, as measured by the mRS-SI at Day 30 9. Functional independence, as measured by the FIM at discharge or Day 10 and Day 90 10. Stroke disability and health-related quality of life, as measured by the Stroke Impact Scale (SIS)-16 at Day 30 and Day 90 11. Hospital length of stay 12. ICU length of stay 13. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) 14. Any safety signals seen on brain imaging 15. Change from baseline in targeted vital signs and ECG 16. Change from baseline in targeted clinical laboratory test results 17. Plasma concentration of balovaptan and its major metabolites (M2 and M3) at specified timepoints 18. Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr) of balovaptan and its major metabolites (M2 and M3) as calculated by non-compartmental analysis (NCA) 19. Maximum observed concentration (Cmax) of balovaptan and its major metabolites (M2 and M3) as calculated by NCA or taken directly from measured concentration 20. Plasma drug concentration 24 hours after the administration of a given dose (C24hr) of balovaptan and its major metabolites (M2 and M3) as calculated by NCA or | — |
Countries
Canada, France, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed