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. Author manuscript; available in PMC: 2014 Feb 1.
Published in final edited form as: Eur Urol. 2012 Nov 23;63(2):309–320. doi: 10.1016/j.eururo.2012.10.007

Table 3.

Negative randomized phase III trials involving endothelin inhibition

Agent N Population Study Arms Endpoints Outcome/Notes
Atrasentan4 941 Nonmetastatic CRPC 1:1 randomization to atrasentan (10 mg PO) or placebo daily Primary: time to disease progression (onset of metastases) There was a non-significant (p = 0.288) 93 day improvement in time to disease progression.
Atrasentan90 809 Metastatic CRPC 1:1 randomization to atrasentan (10 mg PO) or placebo daily Time to disease progression, overall survival Atrasentan did not reduce the risk of disease progression (HR 0.89; 95% CI 0.76 – 1.04; p = 0.136).
Atrasentan SWOG 042191 930 planned (closed early) CRPC with bone metastases All receive docetaxel and prednisone; 1:1 randomization to atrasentan or placebo for up to 52 weeks Survival, progression free survival No differences in median OS (HR 1.01; 95% CI 0.87 – 1.18; p = 0.88), PFS, or response were seen between arms.
Zibotentan M0, Study 15 1,421 Nonmetastatic CRPC 1:1 randomization to zibotentan (10 mg PO) or placebo daily Progression free survival, overall survival Halted early due to lack of efficacy (overall survival 40 months with zibotentan, 39 months with placebo). Screen failures due to previously-unidentified metastases were common.92
Zibotentan M1, Study 14 594 CRPC metastatic to bone, mild or no pain 1:1 randomization to zibotentan (10 mg PO) or placebo daily Overall survival, progression free survival, time to use of opiates, SREs Preliminarily reported as negative as the drug did not significantly improve overall survival (24.5 months with zibotentan, 22.5 months with placebo).
Zibotentan M1C, Study 33 1,052 CRPC metastatic to bone All received docetaxel 1:1 randomization to zibotentan (10 mg PO) or placebo daily Overall survival Preliminarily reported as negative as the drug did not significantly improve median overall survival (20.0 months with zibotentan, 19.2 months with placebo).