Efficacy and Safety Study of Dutasteride Combined With Tolterodine ER or Placebo to Treat Lower Urinary Tract Symptoms (LUTS)

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 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 TRUS

7. IPSS ≥12

8. Post Void Residual Volume < 150 mL at baseline

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

10. 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 micuturitions 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 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 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.