Inclusion Criteria:

- histological confirmation of prostate adenocarcinoma

- documented evidence of bone metastasis on bone scan or MRI

- biochemical progression of prostate cancer

- surgically or medically castrate with serum testosterone ≤2.4nmol/L

- ECOG performance status 0 - 2

- life expectancy of 6 months or more.

Exclusion Criteria:

- radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study
treatment.

- prior targeted cancer therapies (such as gefitinib, bevacizumab)

- systemic radionuclide therapy within 12 weeks of starting study treatment.

- current therapy, within 4 weeks of study entry with potent inhibitors of CYP3A4
(ketoconazole, itraconazole, ritonavir, indinavir, erythromycin, troleandomycin,
clarithromycin, diltiazem and verapamil), inhibitors of CYPs 2D6 and 2C9 (quinidine
and fluconazole), and potent P450 inducers (phenytoin, rifampicin, carbamazepine and
phenobarbitone)

- definite or suspected personal history or family history of adverse drug reactions,
or hypersensitivity to drugs that are endothelin antagonists

- ineligibility for MRI scanning includes standard MRI criteria (for example, metal
implants such as cochlear implants, cardiac pacemakers, heart valves, aneurysm clips
and metal fragments in eyes) and patients known to be allergic to gadolinium-based
MRI contrast agents