Disease relevance of Clazosentan

• CONCLUSIONS: This study indicates that clazosentan reduces the frequency and severity of cerebral vasospasm following severe aneurysmal SAH with the incidence and severity of adverse events comparable to that of placebo [1].
• Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter phase IIa study [1].
• There was no adverse event pattern indicating a specific organ toxicity of clazosentan [1].
• The incidence of new infarctions was 15% in the clazosentan group and 44% in the placebo group (p = 0.130) [1].
• OBJECTIVE: The goal of this study was to investigate the safety and tolerability of the novel endothelin A (ETA) receptor antagonist clazosentan in patients with subarachnoid hemorrhage (SAH) and its potential to reduce the incidence and severity of cerebral vasospasm following surgical clipping of the aneurysm [1].

High impact information on Clazosentan

• Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction [2].
• In Part A, treatment with clazosentan resulted in a reduced incidence of angiographically evident cerebral vasospasm (40% compared with 88% of patients, p = 0.008) [1].
• Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid [3].
• The pharmacokinetics of clazosentan were dose proportional in the dose range investigated [4].
• OBJECTIVE: The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist [4].

Associations of Clazosentan with other chemical compounds

• Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist [4].
• In addition, more selective ET(A) receptor antagonists (ambrisentan, atrasentan, avosentan, clazosentan, darusentan, and sitaxsentan) are undergoing clinical trials [5].

Analytical, diagnostic and therapeutic context of Clazosentan

• CONCLUSIONS: The present data characterize clazosentan as a potent competitive antagonist of ET(A) receptor-mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1 [2].

References