Trial of the Safety and Efficacy of Ozarelix in Patients With Benign Prostatic Hyperplasia (BPH)
Trial of the Safety and Efficacy of Ozarelix in Patients With Benign Prostatic Hyperplasia (BPH)
This is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the
 efficacy of ozarelix compared to placebo in the treatment of lower urinary tract symptoms
 (LUTS) secondary to benign prostatic hyperplasia (BPH) in men as assessed by the
 International Prostate Symptom Score (IPSS) at Week 14.
This is a multi-center, randomized, double-blind, placebo-controlled study.

 Patients who meet the entry IPSS inclusion criteria at Week 0 will be randomized and enroll
 in the double-blind treatment period. Patients will be randomized to one of three treatment
 arms and will receive two 6-month courses of study drug administered on Days 0 and 14 of each
 6-month course. Treatment arms include: ozarelix 30mg + 15mg, ozarelix 15mg + 15mg or placebo
 + placebo. Safety and efficacy assessments will be performed at defined intervals throughout
 the study. At Week 52 all patients on study will be eligible to receive ozarelix for two
 additional courses in the open-label treatment period.
Inclusion Criteria (All must be answered yes):

 1. Has the patient given written informed consent?

 2. Is the patient at least 50 years old?

 3. Is the patient diagnosed with BPH and has he had clinical signs and symptoms of BPH
 for ≥ 6 months?

 4. Does the patient have an IPSS ≥ 13?

 5. Does the patient have a peak urinary flow rate (Qmax) of 4-15 mL/sec (utilizing the
 2-second rule) established on a voided volume of at least 125 mL?

 6. Does the patient have an IPSS QoL score of ≥ 3?

 7. Does the patient have a PSA > 0.8 ng/mL?

 8. For patients with a PSA between 4 and 10 ng/mL or suspicion of prostate cancer, has
 the patient had a diagnostic evaluation (e.g., biopsy, PSA, velocity, etc.) that
 reasonably excludes the diagnosis of prostate cancer?

 9. Is the patient willing to agree not to use any other approved or experimental
 pharmacologic BPH treatments including but not limited to alpha blockers, 5-alpha
 reductase inhibitors, anti-cholinergic preparations or herbal preparations at any time
 during the study?

 10. Is the patient willing to restrict use of PDE 5 inhibitors exclusively to the use of
 Viagra, one dose per week only and with no dosing in the 5 days immediately preceding
 scheduled study visit?

 11. Is the patient willing and able to abide by the protocol?

 12. Does the patient have an IPSS ≥ 13?

 13. Does the patient have an IPSS QoL score of ≥ 3?

 14. Does the patient have a post-void residual ≤ 350cc?

 Exclusion Criteria (all must be answered No):

 1. Does the patient have a history of prostate cancer or a serum PSA >10 ng/mL?

 2. Has the patient had prior prostate or bladder surgery, pelvic surgery (excluding
 hernia repair), pelvic radiation or lower urinary tract malignancy?

 3. Does the patient have a prevoid total bladder volume assessed by ultrasound > 550 mL?

 4. Does the patient have a post void residual urine volume ≥ 350 mL by ultrasound?

 5. Has the patient taken or is the patient currently taking any of the following:

 1. Estrogens, phytoestrogens, androgens, antiandrogens or LHRH agonists within the
 past 4 months (e.g. testosterone gel [Androgel ®1%, Testim ® 1%], testosterone
 buccal [Striant®], oxymetholone [Anadrol®-50], oxandrolone [Oxandrin®],
 esterified estrogen and methyltestosterone [Estratest®]), bicalutamide
 [Casodex®], nilutamide [Nilandron®], flutamide [Eulexin®], leuprolide acetate
 [Lupron®, Eligard®, Viadur®], goserelin acetate [Zoladex®] or,

 2. 5 α-reductase inhibitors within the past 4 months (e.g. finasteride[Proscar®,
 Propecia®], dutasteride [Avodart®]) or,

 3. Alpha blockers or anti-cholinergic preparations within the past 6 weeks (e.g.
 doxazosin [Cardura®], terazosin [Hytrin®], tamsulosin [Flomax®], alfuzosin
 [Uroxatrol®], oxybutinin [Ditropan®], tolteredine [Detrol-LA®], amytriptyline
 [Elavil®, Limbitrol®]) or,

 4. Class 1A (e.g. quinidine, procainamide, disopyramide) or Class III
 Anti-arrhythmic (e.g.sotalol [Betapace®], amiodarone [Cordarone®])

 6. Does the patient have or has the patient ever had a diagnosis of acute or chronic
 prostatitis or chronic pelvic pain syndrome?

 7. Has the patient had a urinary tract infection or instrumentation (e.g catheterization,
 cystoscopy, prostate biopsy) within the past 4 weeks?

 8. Does the patient have a history of urethral stricture, bladder stones, obstructing
 median lobe or neurogenic bladder dysfunction?

 9. Does the patient have microscopic hematuria greater than trace by dipstick urine at
 Visit 1?

 10. Did the patient have a positive drug screening result?

 11. Does the patient have a history of urinary retention?

 12. Does the patient have any serious medical condition (e.g., CHF, poorly controlled
 diabetes (HgbA1c > 9), psychiatric disorder, drug or alcohol abuse) that might
 interfere with his ability to comply with or complete the protocol?

 13. Is the patient's QTc interval on the screening ECG > 450ms, or does he have a family
 history of long QT syndrome?

 14. Does the patient anticipate or plan to have an elective surgery or surgical procedure
 requiring general, spinal or epidural anesthesia during the course of the double-blind
 treatment portion of the study(within the next 12 months)?

 15. Has the patient ever received ozarelix, cetrorelix, tevarelix or degarelix?

 16. Has the patient participated in any other study of an investigational drug or
 treatment for the signs and symptoms LUTS or BPH in the past 12 months?

 17. Has the patient participated in any other clinical research study or study of an
 investigational drug in the past 90 days?