Trial of the Safety and Efficacy of Ozarelix in Participants With Benign Prostatic Hyperplasia (BPH)

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Ozarelix, in Patients With Lower Urinary Tract Symptoms (LUTS) Due to 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.

Participants who meet the entry IPSS inclusion criteria at Week 0 will be randomized and enroll in the double-blind treatment period. Participants 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 participants 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 participant given written informed consent?
2. Is the participant at least 50 years old?
3. Is the participant diagnosed with BPH and has he had clinical signs and symptoms of BPH for ≥ 6 months?
4. Does the participant have an IPSS ≥ 13?
5. Does the participant 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 participant have an IPSS Quality of life (QoL) score of ≥ 3?
7. Does the participant have a PSA > 0.8 ng/mL?
8. For participant 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 participant 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 participant willing to restrict use of Phosphodiesterase 5 (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 participant have an IPSS ≥ 13?
13. Does the participant have an IPSS QoL score of ≥ 3?
14. Does the participant have a post-void residual ≤ 350cc?

Exclusion Criteria (all must be answered No):

1. Does the participant have a history of prostate cancer or a serum prostate specific antigen (PSA) >10 nanogram per milliliter (ng/mL)?

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

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

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

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

   1. Estrogens, phytoestrogens, androgens, antiandrogens or luteinizing hormone-releasing hormone (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®], oxybutynin [Ditropan®], tolterodine [Detrol-LA®], amitriptyline [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 participant have or has the patient ever had a diagnosis of acute or chronic prostatitis or chronic pelvic pain syndrome?

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

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

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

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

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

12. Does the participant have any serious medical condition (e.g., Congestive heart failure [CHF], poorly controlled diabetes (Hemoglobin A1C [HgbA1c] > 9), psychiatric disorder, drug or alcohol abuse) that might interfere with his ability to comply with or complete the protocol?

13. Is the participants corrected QT interval (QTc) interval on the screening electrocardiogram (ECG) > 450ms, or does he have a family history of long QT syndrome?

14. Does the participant 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 participant ever received ozarelix, cetrorelix, teverelix or degarelix?

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