In first of these studies in 809 patients with metastatic CRPC has atrasentan not the risk of disease progression compared to placebo. Most patients radiological bone scan before 12 weeks without concomitant clinical progression forward. In the second study of 941 cancer patients not CRPC, there is a delay Delay of 93 days after treatment, with GSK1292263 a median TTP atrasentan 10 mg was not statistically significant compared to placebo. However, there were large e geographical differences between U.S. and non-US sites observed in this second study. The difference in TTP was 81 and 180 days more U.S. and non-US sites, or after treatment compared to placebo treatment atrasentan. It s believed that the failure of the two Phase III trials of atrasentan may be the design and conduct studies.
JNJ-26481585 Atrasentan was generally well tolerated in these studies. Associated adverse events most common h With treatment were headache, peripheral Said and rhinitis, which reflect the characteristics of fluid retention and vasodilators ETA antagonism. Atrasentan has also studied in combination with docetaxel in a phase I-II CRPC patients with cancer, the maximum tolerated dose of docetaxel in this combination study and vorl INDICATIVE determine effectiveness. MTD dose of docetaxel every 3 weeks in combination with t again Resembled atrasentan 10 mg was 70 to 75 mg ? ?m 2 and PFS and OS were comparable to those observed with docetaxel and prednisone. This combination therapy is currently being studied in a Phase III trial.
Showed a phase I II atrasentan in combination with paclitaxel and carboplatin in patients with chemotherapy naive stage IIIB and IV NSCLC ? that the combination was well tolerated Possible and effective, and the median survival time was comparable to chemotherapy alone. Atrasentan in a Phase I safety in patients with malignant glioma progression studied or relapsed and in a Phase II trial in patients with kidney cancer, locally recurrent or metastatic, the data does not support the further investigation as a single agent in this patient population. Zibotentan Zibotentan is a specific antagonist of the ETA, mix inhibits 125i and 1 binding to cloned human ETA erythroleuk in mouse cells And membranes expressed with an IC50 of 21 nM for ETA and an IC50 value undetectable ETB at concentrations up to 100 mM.
In vitro competitive binding assays suggest that an inhibitor is less strong activity zibotentan t Against other ETA ETA receptor antagonist. However, the relative activity of t in vitro not zwangsl Frequently potency in vivo. Moreover, in contrast to other agents that t the activity Both ETA and ETB, the lack of any effect on ETB zibotentan clinically important than performance relative to ETA. Tats Chlich clinical studies with zibotentan the population pharmacokinetic data showed that the plasma levels of zibotentan after t Glicher oral administration of 10 mg were should reach far beyond the non-clinical and cellular Ren IC50 sufficient ETA antagonism.