Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms

This study is a phase III multinational, multicenter,randomized, double blind, placebo
controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus
abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus
prednisone/prednisolone).The study period will consist of screening/randomization, treatment,
active follow-up with clinic visits, active follow-up without clinic visits, and long-term
follow-up phases. In this study, subjects will receive study treatment (radium-223 dichloride
or placebo in addition to abiraterone acetate plus prednisone/prednisolone for the first 6
cycles followed by abiraterone acetate plus prednisone/prednisolone thereafter) until an
on-study symptomatic skeletal event (SSE) occurs (or other withdrawal criteria are met).
Follow-up will continue for up to 7 years or until the subject dies, is lost to followup, or
withdraws informed consent and actively objects to collection of further data.This study will
be conducted at approximately 150 investigative study centers and approximately 800 subjects
will be enrolled.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Male subjects of age ≥ 18 years

- Prostate cancer progression documented by prostate specific antigen according to the
Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according
to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

- Two or more bone metastases on bone scan within 4 weeks prior to randomization with no
lung, liver, other visceral and/or brain metastasis.

- Asymptomatic or mildly symptomatic prostate cancer.

- Subjects who received combined androgen blockade with an anti-androgen must have shown
prostate specific antigen (PSA) progression after discontinuing the anti-androgen
prior to enrollment.

- Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L).

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Exclusion Criteria:

- Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes,
mitoxantrone and estramustine

- Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg
prednisone/prednisolone bid.

- Pathological finding consistent with small cell carcinoma of the prostate

- History of visceral metastasis, or presence of visceral metastasis detected by
screening imaging examinations

- History of or known brain metastasis.

- Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.

- Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and
during the whole screening period before randomization

- Imminent spinal cord compression based on clinical findings and/or magnetic resonance
imaging (MRI). Subjects with history of spinal cord compression should have completely
recovered

- Use of opiate analgesics for cancer-related pain, including codeine and
dextropropoxyphene, currently or anytime during the 4- week period prior to
randomization.