Dutasteride With Tolterodine ER or Placebo to Treat Lower Urinary Tract Symptoms (LUTS) (LUTS)

A Randomized, Double-blind, Placebo-controlled, Study of Safety and Efficacy of Dutasteride in Combination With Tolterodine ER or Placebo in Men With Lower Urinary Tract Symptoms (LUTS) Including Urgency and Frequency

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).

Study Overview

• Status: Completed
• Conditions: Benign Prostatic Hyperplasia (BPH)
• Intervention / Treatment: Drug: Tolterodine ER 4mg; Drug: Pre-randomization Dutasteride; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic Gateway Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tolterodine ER 4mg; 1:1 randomization to either Dutasteride 0.5mg orally once daily plus Tolterodine ER 4mg orally once daily or Dutasteride 0.5mg orally once daily plus placebo once daily	Drug: Tolterodine ER 4mg; 1:1 randomization to either Dutasteride 0.5mg orally once daily plus Tolterodine ER 4 mg orally once daily or Dutasteride 0.5mg orally once daily plus placebo once daily; Other Names: Detrol LA; Drug: Pre-randomization Dutasteride; All participants were on Dutasteride 0.5mg orally once daily prior to randomization.
Placebo Comparator: placebo; 1:1 randomization to either Dutasteride 0.5mg orally once daily plus Tolterodine ER 4mg orally once daily or Dutasteride 0.5mg orally once daily plus placebo once daily	Drug: Pre-randomization Dutasteride; All participants were on Dutasteride 0.5mg orally once daily prior to randomization.; Drug: Placebo; 1:1 randomization to either Dutasteride 0.5mg orally once daily plus Tolterodine ER 4mg orally once daily or Dutasteride 0.5mg orally once daily plus placebo once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-void Residual (PVR) Volume	To evaluate the safety of dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with symptoms of LUTS: post-voiding residual volume measured via ultrasound.	12 months
Maximum Urine Flow Rate (Qmax).	To evaluate the safety of dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with symptoms of LUTS: maximum urine flow rate (Qmax) measured via uroflowmetry.	12 months
Urine Voided Volume (Voiding)	To evaluate the safety of dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with symptoms of LUTS: urine voided volume (voiding) measured by uroflowmetry.	12 months
Acute Urinary Retention (AUR)	To evaluate the safety of dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with symptoms of LUTS: acute urinary attention (AUR) - inability to urinate requiring catheterization.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overactive Bladder Questionnaire (OABq)	To evaluate the efficacy in men taking dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with LUTS including OAB symptoms: overactive bladder questionnaire (OABq) - 33 questions scored via 1-6 (higher scores indicate more severe symptoms), thus values ranged from 33-198.	12 months
Patient Perception of Bladder Condition (PPBC)	To evaluate the efficacy in men taking dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with LUTS including OAB symptoms: participant reported patient perception of bladder condition (PPBC), one question scored from 1-6, higher scores indicating more severe symptoms.	12 months
International Prostate Symptoms Score (IPSS), Total	To evaluate the efficacy in men taking dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with LUTS including OAB symptoms: total international prostate symptoms score (IPSS) - 7 questions scored from 0-5 (higher score indicating more severe symptoms), thus total scores ranged from 0-35.	12 months
International Prostate Symptoms Score, Voiding Subscore	To evaluate the efficacy in men taking dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with LUTS including OAB symptoms: voiding subscore of international prostate symptoms score (IPSS) - 4 questions scored from 0-5 (higher score indicating more severe symptoms), thus total scores ranged from 0-20.	12 months
International Prostate Symptoms Score (IPSS), Storage Subscore	To evaluate the efficacy in men taking dutasteride 0.5 mg in combination with either tolterodine ER 4mg or placebo for the treatment of men with LUTS including OAB symptoms: storage subscore international prostate symptoms score (IPSS) - 3 questions scored from 0-5 (higher score indicating more severe symptoms), thus total scores ranged from 0-15.	12 months

Collaborators and Investigators

• Sponsor: Siami, Paul F., M.D.
• Collaborators: GlaxoSmithKline; Pfizer
• Investigators: Principal Investigator: Paul F Siami, MD, Deaconess Clinic Research Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 15, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: dutasteride; Benign prostatic hyperplasia (BPH); tolterodine ER
• Additional Relevant MeSH Terms: Pathologic Processes; Urological Manifestations; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Dutasteride; Tolterodine Tartrate
• Other Study ID Numbers: 110983