Dutasteride With Tolterodine ER or Placebo to Treat Lower Urinary Tract Symptoms (LUTS)
Dutasteride With Tolterodine ER or Placebo to Treat Lower Urinary Tract Symptoms (LUTS)
This is an investigator-initiated study of safety, efficacy and tolerability of dutasteride
 given for 18 months, including a 1-year double-blind randomized co-administration with either
 tolterodine ER or placebo in men suffering from lower urinary tract symptoms (LUTS) including
 urgency and frequency, with or without urgency urinary incontinence (i.e., overactive bladder
 (OAB) symptoms).
Men who are treated with an alpha blocker (AB) or 5-alpha reductase inhibitor (5-ARI) for
 benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) often have
 symptoms including urinary frequency and urgency. ABs and 5-ARIs may improve the obstructive
 voiding symptoms but not necessarily the storage symptoms.

 This study will evaluate the safety and efficacy of dutasteride 0.5 mg once daily for 6
 months in an open label fashion. Those patients who continue to report storage urinary
 symptoms, will be randomized to receive dutasteride 0.5 mg once daily for an additional one
 year together with double-blind tolterodine ER 4 mg or matched tolterodine ER placebo once
 daily.
Inclusion Criteria:

 This subject population will consist of males ≥ 50 years of age who have lower urinary
 tract symptoms (LUTS) due to benign prostatic enlargement (BPE) for a minimum of 3 months

 Inclusion criteria at screening:

 1. Subjects who understand and speak English and are able to comply with the protocol,
 complete the diaries, and other study tools

 2. Subject has provided written informed consent and HIPAA authorization

 3. Ambulatory male subjects ≥ 50 years of age

 4. Able to use the toilet without difficulty

 5. History of LUTS due to BPE, as diagnosed by history as well as digital rectal exam
 (DRE), for ≥ 3 months suitable for medical therapy with 5-ARI in combination with
 antimuscarinic drugs

 6. Prostate volume (PV) ≥ 30 cc as measured by transrectal ultrasound (TRUS)

 7. International prostate symptoms score (IPSS) ≥12

 8. Post Void Residual Volume < 150 mL at baseline

 9. Uroflowmetry-Qmax > 5 mL/sec and ≤ 15 mL/sec

 10. Prostate specific antigen (PSA) ≥ 1.5 ng/ml and in normal age-adjusted range. For
 those subjects with an elevated age-adjusted PSA, it is the responsibility of the
 investigator to take standard of care measures to assure reasonable absence of
 prostate cancer

 11. Have an average of ≥ 8 micturitions per 24 hrs

 12. Have an average of 2 episodes of urgency per 24 hrs (defined as those with the Urinary
 Sensation Scale rating of 3 or more)

 Exclusion Criteria:

 1. Concurrent use of 5-ARI therapy within the past 3 months

 2. Concurrent use of alpha blockers within the past 2 weeks

 3. Concurrent use of antimuscarinics within the past 4 weeks

 4. Concurrent use of Phosphodiesterase type 5 (PDE-5) inhibitors on a daily basis

 5. Evidence of chronic inflammation such as interstitial cystitis and bladder stones.

 6. Evidence of untreated urethral stricture disease

 7. Uncontrolled narrow angle glaucoma

 8. Increased post-void residual volume (PVR) defined as PVR > 150 mL

 9. Uroflowmetry-Qmax ≤ 5 mL/sec

 10. Acute urinary tract infection (UTI). These subjects may be treated and re-screened

 11. Acute urinary retention (AUR) requiring catheter within the last 3 months

 12. Previous or planned transurethral resection of the prostate (TURP)

 13. Minimally invasive surgery (MIS) such as transurethral microwave treatment (TUMT),
 transurethral needle ablation (TUNA), laser, or other minimally invasive procedures
 within 12 months. Those patients who in the opinion of the investigator did not
 respond adequately to MIS and fulfill the inclusion criteria are eligible to
 participate

 14. A known diagnosis of prostate cancer.

 15. A known diagnosis of bladder cancer within 5 years of screening. Those patients with
 history of non-muscle invasive bladder cancer who have not had a recurrence in the
 past 5 years are eligible to screen for this study and must maintain continued
 adequate bladder cancer screening at the discretion of the Investigator

 16. Renal or hepatic impairment defined as 2.5 x upper limit of normal. Some isolated
 abnormalities would be left at the discretion of the investigator with always keeping
 in mind to not pose a hazard to the patient.

 17. PSA > 10 ng/mL (if the PSA is greater than 4 ng/mL and less than or equal to 10 ng/mL,
 subjects may be included at the discretion of the Investigator if the PSA has been
 stable and the patient has had a prostate biopsy showing no evidence of prostate
 cancer)

 18. Known or suspected hypersensitivity to dutasteride or tolterodine ER .

 19. Participation in a clinical trial involving an investigational drug, within 30 days
 prior to enrollment.

 20. History of diagnosed gastrointestinal obstruction disease.

 21. Myocardial infarction within the past 8 weeks.

 22. Known or suspected drug and/or alcohol abuse.

 23. Any clinical condition, which, in the opinion of the Investigator, would not allow
 safe completion of the study.