Effects and Safety of OPK-88004 Doses in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (BPH)
Condition: Benign Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia
Intervention: Group-1 (15mg, OPK-88004); Group-2 (25 mg,OPK-88004); Placebo
Intervention description: 15mg, OPK-88004; 25 mg,OPK-88004; Placebo
Intervention MeSH terms: Ascorbic Acid; Methyltestosterone; Androgens; Estrogens, Conjugated (USP)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 114.0
Sex: Male
Minimum age: 45 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety and effectiveness of different doses of OPK-88004
      compared to placebo on serum PSA compared to placebo in men with benign prostatic hyperplasia
      (BPH).
    

Eligibility criteria:

        Inclusion Criteria

        Subjects are eligible if they meet the following criteria:

          1. Present with BPH-LUTS based on disease diagnostic criteria at visit 1

          2. Are men aged 45 years or older at visit 1

          3. Have prostate volume >40 cm3 and <80 cm3 assessed by TRUS at visit 1

          4. Have a PSA >1.5 and <10.0 ng/mL at visit 1. This PSA blood draw must be performed at
             least 1 week after any digital rectal exam (DRE) and/or transrectal ultrasound (TRUS)
             procedures

          5. Subjects with a PSA ≥4.0 and <10.0 ng/mL must have documentation of a negative
             histologic biopsy of carcinoma of the prostate within 12 months of screening (visit
             1). For subjects aged ≤80 years and who have not undergone any invasive urological
             procedure within 6 months, if biopsy has not been performed, then 4Kscore Test value
             must be <7.5% at visit 1

          6. Have laboratory tests within normal limits (with the exception of total serum or free
             testosterone). If laboratory test results are outside normal limits they are
             determined to be not clinically significant at visit 1

          7. Have not received prior treatment with 5-ARIs (finasteride, dutasteride) within the
             past one year for any indication

          8. Have not received herbal BPH preparations within 1 week of visit 1. If the subject is
             currently on such treatment, a 1-week washout period will be required

          9. Agree not to use 5-ARIs, herbal or experimental treatments for BPH, at any time during
             the study. Subjects on daily PDE5i's, alpha-blockers or anticholinergic medications
             for BPH should remain on a stable dose during the study, unless a change in dose is
             medically warranted. Occasional-use PDE5i's for ED are permitted at a stable dose and
             frequency, however should not be taken within 72 hours prior to a study visit

         10. Agree to use an acceptable method of birth control during the study and for 60 days
             after the last dose of IP, unless the female partner is postmenopausal. Postmenopausal
             is defined as a female >50 years of age and 12 months of amenorrhea, or surgically
             postmenopausal

         11. Are reliable and willing to make themselves available for the duration of the study,
             and who will comply with the required study and dosing visits and abide by the
             Clinical Research Site policy and procedure and study restrictions

         12. Have given written informed consent

        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