Effects and Safety of OPK-88004 Doses in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (BPH)

Exclusion Criteria

• •Patients will be excluded from study enrollment if they meet any of the following criteria at visit 1:
• •1. History of any of the following pelvic conditions:
• •* radical prostatectomy, pelvic surgery for removal of malignancy, or bowel resection
• •* pelvic radiotherapy
• •* any pelvic surgical procedure on the urinary tract, including transurethral resection of the prostate (TURP), penile implant surgery
• •* lower urinary tract malignancy or trauma
• •* pelvic surgery or any other pelvic procedure less than 6 months prior to visit 1
• •2. Lower urinary tract instrumentation (including prostate biopsy) within 6 weeks prior to screening PSA blood draw
• •3. History of urinary retention or lower urinary tract (bladder) stones within 1 month of visit 1
• •4. Minimally invasive procedures for BPH, such as prostatic stent, high intensity focused ultrasound (HIFU), holmium laser enucleation of prostate (HoLEP), interstitial laser coagulation (ILC), transurethral electroevaporation of the prostate (TUVP), transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA), photoselective vaporization (PVP), UroLift, within 6 weeks
• •5. Clinical evidence of urinary tract infection or urinary tract inflammation (including prostatitis)
• •6. Intravesical obstruction (eg, intravesical median lobe of the prostate)
• •7. Current neurologic disease or condition associated with neurogenic bladder (eg, Parkinson's disease, multiple sclerosis)
• •8. History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance \<45 mL/min
• •9. Active hepatobiliary disease or serologic evidence of active hepatitis A, B, C, hepatitis E or HIV
• •10. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2X the upper limit of normal (ULN)
• •11. Glycosylated hemoglobin (HbA1c) \>9%
• •12. Hematocrit ≥50%
• •13. HDL-C \<35 mg/dL and LDL-C \>130 mg/dL
• •14. QTcB interval \>450 msec. For heart rates over 75, the ECG may be repeated after 5 minutes of resting quietly
• •15. Abnormality in ECG (eg, left bundle branch block, complete right bundle branch block, or delayed intraventricular conduction with a QRS interval \>120 msec) that in the opinion of the investigator places the subject at an unacceptable risk for study participation, or subject has implanted pacemaker
• •16. History of any of the following cardiac/coronary conditions within 90 days:
• •* history of myocardial infarction or coronary artery bypass graft
• •* percutaneous coronary intervention
• •* stroke
• •17. Any evidence of heart disease (NYHA ≥Class II, Appendix 4) within 6 months, or are receiving treatment for congestive heart failure (CHF)
• •18. Any supraventricular or ventricular arrhythmia with uncontrolled ventricular response (mean heart rate \>100 bpm) at rest despite medical therapy
• •19. Systolic blood pressure \>160 or \<90 mm Hg or diastolic blood pressure \>100 or \<50 mm Hg as determined by a sitting measurement (if stress is suspected, retest up to two times under basal conditions), or malignant hypertension
• •20. Have a history or presence of prostatic carcinoma, as well as any conditions that may be exacerbated by androgenic medications such as (but not limited to) epilepsy, seizures, convulsions, migraine or polycythemia
• •21. History of cancer within the previous 5 years, except for excised superficial lesions (such as basal cell carcinoma and squamous cell carcinoma of the skin)
• •22. History of drug, alcohol, or substance abuse within 6 months
• •23. Have an alcohol intake of ≥3 units/day or ≥14 units/week during the study (1 unit = 12 ounces of beer, 5 ounces of wine, 1.5 ounces of distilled spirits)
• •24. Any condition that would interfere with subject's ability to provide informed consent or comply with study instructions, would impair ability to perform the study assessments, or would place subject at increased risk, or might confound the interpretation of the study results
• •25. Current treatment with androgens, antiandrogens, estrogens, or anabolic steroids within the prior 1 month. Any prior or current treatment with LHRH agonists/antagonists
• •26. Current treatment with potent CYP3A4 inhibitors such as itraconazole or ritonavir
• •27. Have taken prescription or over-the-counter medications to promote weight loss within the prior 3 months
• •28. Any prior use of OPK-88004 Allergic to any component of OPK-88004