Efficacy and Safety Study of Dutasteride Combined 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.

• Drug: dutasteride 0.5 mg, used with tolterodine ER 4mg or placebo

  dutasteride 0.5 mg orally once daily for six months, followed by randomization in a 1:1 ratio into two parallel groups of

  1. dutasteride 0.5 mg once daily with tolterodine ER 4 mg orally daily for one year or
  2. dutasteride 0.5 mg once daily with tolterodine ER placebo orally daily for one year
• Drug: dutasteride
  open-label dutasteride 0.5 mg once daily for 6 months

• Active Comparator: dutasteride 0.5 mg
  open-label dutasteride 0.5 mg once daily for 6 months
  Intervention: Drug: dutasteride
• Experimental: dutasteride 0.5 mg, tolterodine ER 4 mg, placebo
  dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo
  Intervention: Drug: dutasteride 0.5 mg, used with tolterodine ER 4mg or placebo

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.

• GlaxoSmithKline
• Pfizer