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.

Study Overview

• Status: Terminated
• Conditions: Benign Prostatic Hyperplasia (BPH); Lower Urinary Tract Symptoms (LUTS)
• Intervention / Treatment: Drug: Placebo; Drug: ozarelix

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92660
      • California Professional Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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?

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo + Placebo; Participants will receive Placebo + Placebo on Days 0 and 14 of each 6-month course.	Drug: Placebo; Identical placebo is also provided and reconstituted using diluent containing 0.1% saline solution.
EXPERIMENTAL: 15 mg Ozarelix + 15 mg Ozarelix; Participants will receive 15 mg Ozarelix + 15 mg Ozarelix on Days 0 and 14 of each 6-month course.	Drug: ozarelix; One single-dose vial contains 16.5 mg of ozarelix. The drug is reconstituted with 1.3 mL of diluent.
EXPERIMENTAL: 30 mg Ozarelix + 15 mg Ozarelix; Participants will receive 30 mg Ozarelix + 15 mg Ozarelix on Days 0 and 14 of each 6-month course.	Drug: ozarelix; One single-dose vial contains 16.5 mg of ozarelix. The drug is reconstituted with 1.3 mL of diluent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline International Prostate Symptom Score (IPSS) Score at Week 14	IPSS is a validated self-administered index for grading benign prostatic hyperplasia (BPH)-related signs and symptoms. It consists of a set of seven questions. A total score of 1-7 indicates mild disease, 8-19 moderate disease and 20-35 severe disease.	Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline IPSS (Including Sub-scores) at Week 52	The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). 1) Voiding- The subscale voiding score is the sum of the responses to 4 voiding symptoms questions (incomplete emptying, intermittency, weak stream, and straining). 2) Storage- The subscale storage score is the sum of the responses to 3 storage symptoms questions (frequency, urgency, and nocturia). Voiding and Storage: the lowest and highest possible scores range from 0 to 15 (mildly symptomatic to severely symptomatic). Voiding and Storage: each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. And 3) QoL assessment was a single question asking the participant how he would feel about tolerating his current level of symptoms for the rest of his life. The lowest and highest possible score ranges from 0 to 6 (very pleased to terrible).	Week 52
Change From Baseline Benign Prostatic Hyperplasia Impact Index (BPHII) Score at Week 14 and Week 52	BPH Impact Index (BII) is used to assess the impact of BPH on various aspects of health. This 4 question self administered index uses a scoring range from 0 (best) to 13 (worst).	Weeks 14 and 52
Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) Response at Week 52	The self administered LUTS GAQ is a "yes" or "no" response to a question asking whether overall improvement in LUTS will be observed during the treatment period.	Week 52
Change From Baseline Maximum Urine Flow (Qmax) at Week 14 and Week 52	Qmax was measured by free flow uroflowmetry. Qmax is defined as the peak urine flow rate (measured in milliliter (mL)/second using a standard calibrated flowmeter). For a Qmax to be considered valid, the voided volume had to be at least 125 mL. The uroflowmeter is to be calibrated weekly.	Week 14 and Week 52
Change From Baseline International Index of Erectile Function-15 (IIEF-EF) Score at Week 14 and Week 52	IIEF-EF is defined as the sum of the scores for Questions 1-5 and 15 of the IIEF questionnaire. This recall instrument is self-administered by the participant. Individual questions are graded from 1 to 5 with a maximum total score of 30. Lower IIEFEF scores represent diminished erectile function. Men with a score of ≥ 26 are interpreted as having normal erectile function.	Week 14 and Week 52
Change From Baseline International Prostate Symptom Score - Quality of Life (IPSS-QOL) at Week 14 and Week 52	IPSS QOL is a disease-specific quality of life question, referred to as IPSS Question 8. Participants with an IPSS QOL of <3 at screening will be excluded from this study. The rating is as follows: 0=delighted, 1=pleased, 2=mostly satisfied, 3=mixed, 4=mostly dissatisfied, 5=unhappy, 6=terrible.	Week 14 and Week 52
Number of Participants With Treatment-Emergent Adverse Events		Up to 104 weeks

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2008
• Primary Completion (ACTUAL): January 20, 2010
• Study Completion (ACTUAL): January 20, 2010

Study Registration Dates

• First Submitted: August 26, 2008
• First Submitted That Met QC Criteria: August 27, 2008
• First Posted (ESTIMATE): August 28, 2008

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: LUTS; BPH; Lower urinary tract symptoms (LUTS)
• Additional Relevant MeSH Terms: Pathologic Processes; Urological Manifestations; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms
• Other Study ID Numbers: SPI-153-08-1