Study of Teverelix DP on Prostate Volume, Urinary Function and Clinical Outcomes Following Acute Urinary Retention

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)