Maintaining Suppression of Testosterone With Transdermal Estradiol Gel
Maintaining Suppression of Testosterone With Transdermal Estradiol Gel
The objective of this clinical study is to evaluate the safety and efficacy of three
 different doses of BHR-200 (0.36% transdermal estradiol gel) compared to placebo for the
 maintenance of testosterone (T) suppression in men with advanced androgen-sensitive prostate
 cancer.
This is a multi-center, randomized, double-blind, placebo-controlled, dose finding study in
 men with advanced androgen-sensitive prostate cancer. Patients who give informed consent will
 have screening evaluations, and if fulfilling the entry criteria, will be randomized to one
 of 4 treatment groups: 1mL, 2mL or 3mL of 0.36% BHR-200 (transdermal estradiol gel) or
 Placebo. Study drug will be initiated on the day they were scheduled to receive next depot
 GnRH agonist injection. Patients will be offered low-dose radiation to aid in the prevention
 of gynecomastia. Patients will apply the study drug once per day. The first dose of study gel
 will be applied under the supervision of the PI/designee. Subsequent doses will be
 self-administered daily by the patient until he is no longer chemically castrated
 (testosterone levels increase above 50 ng/dL), a rise over baseline PSA of > 0.5 ng/mL is
 observed, or he has completed 52 weeks of study drug administration. At the conclusion of
 study participation, patients will be advised to resume standard of care treatment under the
 supervision of their healthcare provider. While on treatment, patients will be evaluated at
 Day 1 and every 2 weeks, for the first 24 weeks and every 4 weeks thereafter with a final
 post-treatment follow-up visit 2 weeks (+/- 1 week) post last dose administration.
Inclusion Criteria:

 1. Males, Ages 18 and older

 2. Body Mass Index (BMI) between 18 and 35 kg/m2 (inclusive)

 3. Not currently hospitalized

 4. Clinical indication of adenocarcinoma of the prostate evidenced by a biopsy report on
 record

 5. At present receiving ADT treatment with a GnRH agonist for at least 2 months but not
 longer than 36 months without interruption - Note: If the patient received GnRH
 agonist treatment prior to the treatment described under 5, there must be evidence of
 a period without GnRH agonist treatment for a minimum of 2 months prior to starting
 the present treatment as is seen, for example with intermittent treatment regimens.

 6. Able to initiate Screening procedures 2 weeks prior to the next scheduled injection
 with a GnRH agonist

 7. Willing to discontinue current ADT regimen for the duration of the study

 8. T level less than 50 ng/dL at Screening

 9. WHO/ECOG performance status of 0 or 1

 10. Life expectancy of at least 1 year

 11. Adequate renal function demonstrated by having normal blood urea nitrogen (BUN) and
 Creatinine Screening lab values

 Exclusion Criteria:

 1. History or presence of allergic or adverse response to estradiol

 2. Presence of symptomatic metastatic disease, risk of spinal cord compression or urinary
 obstruction

 3. History within the past 2 years of deep vein thrombosis (DVT), pulmonary embolism
 (PE2), a known thrombophilic disorder (eg.protein C, protein S, or antithrombin
 deficiency), or cerebrovascular accident (CVA)

 4. History within the past 2 years of myocardial infarction or a coronary vascular
 procedure (e.g. percutaneous coronary intervention, coronary artery bypass graft)

 5. History of congestive heart failure

 6. Use of any investigational drug, biologic, or device within 28 days prior to the first
 dose of study gel

 7. Use of any of the following known inducers or inhibitors of cytochrome P450 3A4
 (CYP3A4): phenobarbital, carbamazepine, rifampin, erythromycin, clarithromycin,
 ketoconazole, itraconazole, ritonavir, St. John's Wort preparations (Hypericum
 perforatum), and grapefruit juice

 8. Hematological parameters (Hematocrit or Hemoglobin) outside 20% of the upper or lower
 limits of normal at Screening

 9. Active skin rash, sunburn, or other skin disorder on the upper arm(s) that requires
 treatment or may affect skin absorption of study gel

 10. Resting uncontrolled hypertension (HTN) (160/100 mmHg) at Screening

 11. Co-existent malignancy or a history of malignancy during the past 5 years, with the
 exception of basal and/or squamous cell carcinoma of the skin

 12. Any other significant concurrent illness or disease or condition that in the opinion
 of the Investigator might interfere with the patient's ability to receive the
 treatment outlined in the protocol or might put him at additional risk