E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with lower urinary tract symptoms due to Benign Prostatic Hyperplasia
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004446 |
E.1.2 | Term | Benign prostatic hyperplasia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and efficacy of a single treatment of 100 U, 200 U, or 300 U BOTOX® compared with placebo injected into the prostate to treat lower urinary tract symptoms in patients due to benign prostatic hyperplasia.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male, aged 50 years and older 2. Weight at least 50 kg 3. Lower urinary tract symptoms in patients due to benign prostatic hyperplasia based on medical history and digital rectal exam, respectively. 4. Lower urinary tract symptoms (except incontinence) for at least 3 months by patient report. These symptoms may include any or all of the following obstructive or irritative symptoms: weak urinary stream, prolonged voiding, abdominal straining, hesitancy, intermittency, incomplete bladder emptying, dribbling, frequency, nocturia, urgency, bladder pain, and dysuria. 5. International Prostate Symptom Score (IPSS) greater than or equal to 12 at the screening visit (day -14). 6. Total prostate volume by transrectal ultrasound of at least 30 mL but not greater than 100 mL determined at the screening visit (day -14). 7. Peak urinary flow rate of at least 5 mL/sec, but not greater than 15 mL/sec with a voided urine volume of at least 125 mL at the screening visit (day -14). 8. Post void residual urine volume less than 200 mL measured by ultrasound or bladder scan at the screening visit (day -14). 9. If engaging in sexual activities, all patients must use a male condom for 3 months post-treatment irrespective of other contraceptive methods (e.g., vasectomy). Patient with a partner of child-bearing potential must also use a spermicide gel or cream with the male condom, if patient has not had a vasectomy or the female partner is not using an oral, patch, injectable contraceptive or intrauterine device (if she has not had a tubal ligation or hysterectomy). 10. Written informed consent obtained including information regarding the collection, use, disclosure and protection of their personal information (Canadian sites only) or Data Protection Consent (European sites only). 11. Patient is registered in the French social security system and fulfils necessary requirements as required by local law (French sites only). 12. Able and willing to comply with study instructions and visit schedule. |
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E.4 | Principal exclusion criteria |
1. Previous prostate surgery, including minimally invasive procedures (e.g., transurethral needle ablation, transurethral microwave therapy) 2. Any prostate biopsy within 6 weeks of the screening visit (day -14). Patients will be allowed to be re-screened a minimum of 6 weeks after a negative biopsy result is documented. All other protocol inclusion and exclusion criteria must be met. 3. Prominent medial lobe at the screening visit (day -14), as determined by the investigator’s opinion (e.g., transrectal ultrasound or previous cystoscopy). 4. Previous or current diagnosis of prostate cancer. 5. Patient with a Prostate Specific Antigen (PSA) greater than 10 μg/L may not be enrolled. Patients with a total PSA greater than or equal to 4.0 μg/L and less than or equal to 10 μg/L must have prostate cancer ruled out to the satisfaction of the investigator according to local site practice. 6. Alpha-adrenergic antagonists within 15 days prior to the screening visit (day - 14) and patient is unwilling to remain off the medication for duration of the study. 7. Medications in the following classes within 15 days of the screening visit (day - 14) and patient is unwilling or unable to remain off chronic use of these medications for the duration of the study. • Alpha-adrenergic agonists • Drugs with anticholinergic/antimuscarinic activity if they are indicated for any form of urinary symptoms or bowel disease • Antispasmodics, including those indicated for gastrointestinal discomfort 8. Medication in the following classes within 90 days of the screening visit (day - 14) and throughout the duration of the study. • 5-alpha-reductase inhibitors • Androgens • Drugs with anti-androgenic activity (e.g., spironolactone) 9. Phytotherapy taken for the treatment of prostate diseases or non-specific urinary symptoms within 30 days of the screening visit (day -14) and throughout the duration of the study. 10. Medications with anti-platelet or anti-coagulant (e.g., including acetylsalicylic acid) effect are prohibited for a minimum of 3 days or longer according to clinical judgment of the investigator, prior to any study treatment until the end of the day of treatment (refer to Section 8.2.2 Prohibited Medications/Treatments for details). 11. Symptomatic prostatitis (acute or chronic) within 12 months of the screening visit (day -14), as determined by patient history. 12. History or evidence of any urologic abnormalities (e.g., urethral stricture), bladder surgery, or disease (other than BPH) that may impact bladder function. 13. Recurrent urinary tract infections (UTI) defined as 2 or more episodes in the 12 months prior to the screening visit (day -14) or UTI in the last 6 months prior to randomization/ treatment visit (day 1). 14. Urinary infection defined as a bacteriuria count of >10^4 CFU/mL conjoint with leukocyturia >5/hpf at the screening visit (day -14). In addition, patients with a lower bacteriuria count who, in the opinion of the investigator, have a UTI should also be excluded. 15. Urinary tract infection (symptomatic or asymptomatic) at the treatment visit (day 1), prior to randomization. Asymptomatic urinary tract infection defined as positive nitrites, blood and/or leukocyte esterase on urine dipstick reagent test strip. 16. History or evidence of interstitial cystitis based on the investigator’s opinion. 17. History or evidence of bladder cancer. 18. History or evidence of stones in the bladder are excluded. Patients with current evidence of asymptomatic stones in the kidney may be enrolled if no active intervention is planned. 19. History or evidence of urinary incontinence not directly related to benign prostatic hyperplasia (e.g., sphincter conditions). 20. Acute urinary retention or previous use of indwelling catheter for urinary retention within 3 months of the screening visit (day -14), except if urinary retention was associated with unrelated surgery and/or general/regional/local anesthesia and has resolved without any further intervention. 21. Urethral instrumentation within 15 days of the screening visit (day -14), including urodynamic assessments (e.g. bladder catheterization). 22. Previous radiation therapy to the pelvis. 23. Patient with hematuria (>5 RBC/hpf) at the screening visit (day -14) or a history of hematuria is excluded: 1) if the hematuria is due to a pathological condition in the investigator’s opinion, or 2) if the hematuria is uninvestigated. 24. Diagnosis or findings at the screening visit (day -14) consistent with a known primary neurologic condition known to affect bladder function (e.g. multiple sclerosis, Parkinson’s disease, spinal cord injury, stroke). Please refer to protocol for criterion 25 to 32.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change of International Prostate Symptom Score (IPSS) score from baseline at 12 week visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |