Study of VERU-944 to Ameliorate Hot Flashes in Men With Advanced Prostate Cancer

Inclusion Criteria

• Be over 18 years of age;
• Be able to communicate effectively with the study personnel;
• Have histologically confirmed prostate cancer;
• Have been treated with an LHRH agonist or LHRH antagonist for at least the 3 months prior to randomization;
• Be continued on an LHRH agonist or LHRH antagonist throughout this study;
• Have experienced hot flashes for at least one month prior to study entry;
• Have moderate or severe vasomotor symptoms (hot flashes) (defined as a minimum of 4 moderate to severe hot flashes per day or 12 per week at baseline);
• ECOG performance status of 0 to 2
• Be willing to uses electronic data capture for the relevant medical events
• Must be at least 80% compliant during the screening period
• Subjects must agree to use acceptable methods of contraception:
• If their female partners are pregnant or lactating, acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication must be used. Acceptable methods are: Condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia), a condom with spermicidal foam/gel/film/cream/suppository should be used.
• If the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository).
• If the female partner has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used.
• If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used.
• Subject is willing to comply with the requirements of the protocol through the end of the study.

Exclusion Criteria

• Have a serum total testosterone concentration > 50 ng/dL at screening;
• Known hypersensitivity or allergy to estrogen or estrogen like drugs;
• Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk;
• Subjects with a personal history of abnormal blood clotting or thrombotic disease, including venous or arterial thrombotic events such as a history of stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE);
• Any subjects, as determined by a central laboratory, that have a:
• Factor V Leiden gene mutation
• Prothrombin gene mutation
• Uncontrolled symptomatic congestive heart failure (NYHA Class III - IV), unstable angina pectoris, cardiac arrhythmia, or uncontrolled atrial fibrillation;
• History of MI
• The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study;
• Receive