Actelion Ltd, a biopharmaceutical company, announced that preliminary analysis of the dose-finding study Conscious-1 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid haemorrhage) indicates that all three doses of i.v clazosentan tested (15, 5 and 1 mg/hour) have reached statistical significance versus placebo for the primary endpoint, the reduction in the occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography at day 9 (plus/minus 2 days) post-aneurysm rupture compared to placebo.
The effect was dose-related and most significantly seen with the dose of 15 mg/hour, a relative risk reduction compared to placebo of 65 percent (p<0.0001). In the study, the significant reduction in cerebral vasospasm did not translate into an overall clinical benefit as assessed by the chosen key secondary composite endpoint: occurrence of morbidity/mortality (death, new cerebral infarcts, delayed ischemic neurological deficit, rescue therapy) up to week 6.
In the study, treatment with clazosentan was associated with more adverse events than placebo, mainly related to vasodilatory effects such as hypotension and fluid retention.
Isaac Kobrin, MD and Head of Clinical Development, commented: "The information generated from the preliminary analysis of CONSCIOUS-1 demonstrates significance in terms of clazosentan decreasing cerebral vasospasm in a dose-related fashion."
Isaac Kobrin concluded: "A full data analysis and consultation with clinical experts is essential to better understand the apparent disconnect in this study between the significant reduction in cerebral vasospasm and clinical outcome assessed by the endpoint chosen. This full data analysis will determine the future development path."
Conscious-1 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid haemorrhage) was a multi-centre, international, double-blind, randomized, placebo-controlled, parallel group, dose-finding study to evaluate the efficacy of 3 dose levels of clazosentan (15, 5 and 1mg/hour) in preventing the occurrence of cerebral vasospasm following SAH who underwent either clipping or coiling to stop the initial aneurismal bleed, assessed by angiography. As a secondary endpoint, the study also evaluated the ability of clazosentan to reduce the occurrence of early morbidity/mortality as well as overall safety and tolerability of the drug.
Conscious-1 recruited 413 patients in 52 centres in 11 countries worldwide and was initiated after promising pre-clinical and clinical data that was published in the Journal of Neurosurgery in July 2005.