Acute Urinary Retention, Benign Prostate Hypertrophy(BPH)
Conditions
Keywords
Prostatic Diseases, Teverelix, Acute urinary retention, Benign Prostate Hypertrophy, AUR, BPH
Brief summary
This randomized, double-blind, placebo-controlled Phase 2 study is evaluating Teverelix DP in men following a first episode of acute urinary retention (AUR) associated with benign prostatic hyperplasia (BPH), a population at risk of recurrent urinary retention and subsequent surgical or minimally invasive intervention. The study is designed to evaluate the effects of Teverelix DP on total prostate volume and urinary function and to prospectively evaluate clinically meaningful outcomes including recurrent AUR, BPH-related surgical or minimally invasive intervention, protocol-defined treatment failure and clinical benefit. Participants will be randomized to one of four treatment groups evaluating two active Teverelix DP regimens: 90 mg administered intramuscularly (IM) and 120 mg administered subcutaneously (SC) and their respective matched placebo controls. The primary endpoint is percent change from baseline in total prostate volume (TPV) at Week 12. Participants will continue to be evaluated during the 28-week treatment period for urinary function and prospectively defined clinical outcomes, including recurrent AUR, BPH-related intervention, treatment failure and clinical benefit, and will be followed through Week 52 for protocol-defined longer-term assessments and safety follow-up. The study is designed to characterize biological activity, urinary function, clinical outcomes, safety and the relative treatment effects of the two Teverelix DP regimens to inform dose and route selection and subsequent clinical development.
Detailed description
An interim analysis of the primary endpoint will be conducted after at least 50% of patients have completed their 12-week visit. The interim analysis may also be used to inform future development strategy for Teverelix DP. Should the interim data demonstrate supportive safety and pharmacodynamic trends, the Sponsor may consider expansion of the clinical development program into a confirmatory Phase 3 trial.
Interventions
DRUGTeverelix DP
Single dose at Day 1 of 90 mg injection IM
DRUGTeverelix DP Placebo
Single dose at Day 1 of 90 mg injection IM
Sponsors
Antev Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male aged 45 years or older 2. Having given his written consent 3. Successful TWOC as defined by successful voiding with a minimum residual volume 4. Having had a first episode of spontaneous acute urinary retention within 6 days of study screening visit. 5. Prostate volume \>40 g (assessed by TRUS) 6. Patients may initiate or continue alpha-blocker therapy at or before randomization. The same agent and dose should be continued throughout the treatment period where possible 7. Agrees to practice contraception during the entire study treatment period and for 3 months after the last dose of IMP is administered: 1. Either by using double barrier contraception and in compliance with local guidelines, 2. or, is truly sexually abstinent, when this is in line with the preferred and usual lifestyle of the patient i. Note: Periodic abstinence \[e.g. calendar, ovulation, symptothermal, postovulation methods for the female partner with childbearing potential\] and withdrawal are not acceptable methods of contraception. 8. Must be treatment naïve to GnRH analogues
Exclusion criteria
1. Participated in another investigational study within 3 months before recruitment 2. AUR due to i.e. postoperative retention following major abdominal/pelvis/spinal surgery 3. Neurological related AUR 4. Contraindication to the use of alpha blockers 5. Previous prostate or urethral surgery 6. Previous histological or clinical diagnosis of prostate cancer 7. Any unstable co-existing medical condition 8. Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values: 1. Liver function test (aspartate aminotransferase \[ASAT/SGOT\], alanine aminotransferase \[ALAT/SGPT\]), exceeding \>2X the upper limit of the normal (ULN) range 2. Total bilirubin exceeding \>1.5X the upper limit of the normal (ULN) range 3. An estimated glomerular filtration rate (eGFR) \< 30 mL/min, based on creatinine clearance calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation normalised to an average surface area of 1.73m2, at the screening visit. 9. Has congenital long QT syndrome or ECG abnormalities at screening of: 1. Q-wave infarction, unless identified ≥6 months before screening 2. Fridericia corrected QT interval (QTcF interval) \>480 msec. If QTcF is prolonged in a patient with a pacemaker, the patient may be enrolled in the study upon discussion with the project clinician 3. If the QTcF interval is 450-480 msec, inclusive, in a patient with current use of medications with known effects on QT interval, the patient may be enrolled in the study following discussion with the Medical Lead Note: Cardiac arrhythmia grading: * Bradyarrhythmias (HR \<60/min) * Tachyarrhythmias (HR \>100/min * Supraventricular arrhythmias - arrhythmias that originate in the sinoatrial node, atrial myocardium or atrioventricular node (regular QRS complex) * Ventricular arrhythmias - arrhythmias that originate below the atrioventricular node (wide QRS complex) 10. History or current evidence of alcohol or drug abuse within the last 12 months 11. Prostate Specific Antigen (PSA) greater than 20ng/ml 12. Use of suprapubic catheterization after failed urethral catheterization 13. Neurogenic bladder dysfunction, confirmed or suspected, irrespective of etiology 14. Isolated bladder neck disease 15. Acute or chronic prostatitis 16. Confirmed or suspected urethral stricture 17. Known bladder stones 18. Use of the following medications prior to and during study participation: 1. Any other IMP (within 3 months of enrolment) 2. Herbal medications known to have anti-androgenic effects (e.g. red reishi, licorice, white peony, green tea, spearmint, black cohosh, chaste tree, saw palmetto, etc) (within 3 months of enrolment) 3. Anti-androgen therapy (within 3 months of enrolment) 4. T replacement therapy (within 3 months of enrolment) 5. 5α-reductase inhibitor treatment etc. (within 25 weeks prior to screening: dutasteride; within 12 weeks prior to screening: finasteride (and others)) 6. Bethanechol chloride 7. Any other medication or herbal product that may affect hormone levels and might, therefore, confound interpretation of the study results (e.g. St. John's wort) (within 3 months of enrolment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change from Baseline in Total Prostate Volume (TPV) at Week 12 | Change from baseline to Week 12 | Percent change from baseline in total prostate volume as assessed by transrectal ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the AUR clinical benefit rate of Teverelix DP after a single dose | From dosing to week 52 | The proportion of patients meeting all of the following criteria during the 28-week treatment period and the 52-week observation period: * No relapse of AUR; * No need or indication for surgical intervention; and * No occurrence of treatment failure (PVR \>300 mL with Qmax \<10 mL/sec). |
| Evaluate the durability of prostate volume reduction following a single dose of Teverelix DP | Change from baseline to week 52 | Percent change in total prostate volume |
| Change from baseline in post-void residual volume (PVR) (mL), assessed by ultrasound. | Change from baseline to week 28 | — |
| Change from baseline in maximum urinary flow rate (Qmax) (mL/sec), using Uroflowmetry. | Change from baseline to week 28 | — |
| Explore the correlation between change prostate volume and change in post-void residual volume (PVR) (mL) | Change from baseline to week 28 | — |
| Explore the correlation between change prostate volume and change in maximum urinary flow rate (Qmax) (mL/sec) | Change from baseline to week 28 | — |
| Incidence of AUR recurrence according to Teverelix dose (90 mg vs 120 mg) and route of administration (IM vs SC) | From Day 1 through study completion (an average of 1 year) | Identifying the optimal dosing regimen and route of administration from the following; 90 mg or 120 mg of Teverelix DP and intramuscular (IM) or subcutaneous (SC). |
| To assess time to Post-void residual (PVR) >60% of total bladder volume, measured by ultrasound. | From Day 1 through study completion (an average of 1 year) | PVR volume measurements will be taken at various timepoints in the study to assess the time taken for PVR \>60% of total bladder volume |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of Teverelix DP in men with AUR secondary to benign prostatic hyperplasia (BPH). | From Day 1 through study completion (an average of 1 year) | Safety and tolerability will be evaluated by the incidence, nature, severity, and relationship to study treatment of adverse events (AEs) and serious adverse events (SAEs), together with assessments of clinical laboratory parameters, vital signs, physical examinations, electrocardiograms (ECGs), concomitant medications, and any clinically significant findings observed throughout the study. |
| To assess progression of BPH-related symptoms. | Change from Day 1 through study completion (an average of 1 year) | The International Prostate Symptom Score (IPSS) will be used to assess progression of BPH-related symptoms. The total IPSS score is calculated by summing the scores from all seven questions, giving a range of 0 to 35. Change in IPSS score will be reviewed. Lower scores indicate fewer or less severe urinary symptoms, and higher scores indicate more severe urinary symptoms. |
| To assess the incidence of BPH-related minimally invasive procedures or surgeries. Procedure/surgery review will completed at visits throughout the study. | From Day 1 through study completion (an average of 1 year) | — |
Contacts
CONTACTRuhena Chowdhury, PhD
Outcome results
None listed