A Randomized, Double Blind, Placebo Controlled, Multicenter Efficacy and Safety Study of Toremifene Citrate for Prevention of Bone Fractures in Men With Prostate Cancer on Androgen Deprivation Therapy

Inclusion Criteria:

To be eligible for participation in this study, subjects must meet all of the following
criteria (minor deviations may be discussed with the medical monitor for possible
inclusions):

- Give voluntary, signed informed consent in accordance with institutional policies

- Be male, aged ≥ 50 years

- Have histologically documented prostate cancer. Subjects with metastatic prostate
cancer may still be considered for the study as long as they are not disqualified by
other inclusion/exclusion criteria and there is a reasonable expectation that their
medical condition will not interfere with the objectives of the study and that
adequate follow-up and compliance with the study protocol can be achieved for the
full 24-month duration of the study.

- Have been on:

- ADT treatment (either luteinizing hormone-releasing agonist [LHRHa] or
orchiectomy) for at least 6 months; Or

- Intermittent LHRHa for at least the preceding 12 months is acceptable, but
subjects must be maintained on uninterrupted treatment for the duration of this
study once they are randomized into the study.

- Be aged ≥ 70 years or have BMD of lumbar spine or femoral neck at or below the
specified thresholds for study entry:

- Hologic BMD (g/cm2): L1-L4 - 0.926; Femoral neck - 0.717

- Lunar BMD (g/cm2): L1-L4 - 1.050; Femoral neck - 0.840

- Serum prostate-specific antigen (PSA) ≤ 4 ng/mL

- Have a Zubrod performance status ≤ 1

- Subject weight < 300 lbs (weight limitation of DEXA equipment)

- Agree to complete a daily diary of medication intake and to provide tablet containers
for accurate counts

- Agree to use an effective method of contraception, if the partner is of childbearing
age, while on study

- Have adequate bone marrow, liver and renal function:

- White blood cell (WBC) count ≥ 3,000/mm3;

- Platelet count ≥ 100,000/mm3;

- Bilirubin ≤ 1.5 mg/dL;

- AST and ALT < 2x upper limit of normal;

- Serum creatinine ≤ 2.0 mg%.

Exclusion Criteria:

Subjects with any of the following will not be eligible for enrollment:

- Taking bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid
hormone (PTH), Forteo® (teriparatide), calcitonin, or oral glucocorticoids within 45
days of randomization

- Have any disease or condition that would preclude an accurate evaluation of
radiographs of the thoracic and lumbar spine (at least eight evaluable vertebrae in
the range T4 to L4) [for example, severe scoliosis, or sequelae of orthopedic
procedures or other surgery]

- Have > 4 vertebral fragility fractures

- Have any history of other carcinomas within the last 5 years (except nonmelanoma
cutaneous malignancies and superficial bladder cancer with no evidence of recurrence
which will not be excluded). NOTE: Patients with cancers other than nonmelanoma
cutaneous malignancies and superficial bladder cancer with no evidence of tumor
recurrence for at least 5 years after definitive treatment will not be excluded from
this study.

- Have Paget's disease of bone

- Have active systemic viral, bacterial or fungal infections requiring treatment

- Have, in the judgment of the investigator, a clinically significant concurrent
illness or psychological, familial, sociological, geographical or other concomitant
condition that would not permit adequate follow-up and compliance with the study
protocol for the full 24-month duration of the study

- Received treatment with other investigational agents within 30 days prior to
randomization

- Taking finasteride (e.g., Proscar®), dutasteride (e.g., Avodart®), Danocrine®
(danazol) or testosterone-like supplements, such as dehydroepiandrosterone (DHEA)
[subject is eligible if he stops these agents for a total washout of 45 days prior to
randomization and agrees not to use these agents for the duration of the study]

- Taking herbal medicine or dietary supplements for prostate health, such as PC SPES
and saw palmetto (also known as Serenoa repens) [subject is eligible if he stops
these agents for a total washout of 45 days prior to randomization and agrees not to
use these agents for the duration of the study]. Lycopene and selenium are not
prohibited and no washout is required.

- Have a history of thromboembolic disease including deep vein thrombosis or pulmonary
embolus

- Have a history of chronic hepatitis or cirrhosis

- Have received prior treatment with toremifene