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

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Pfizer
Information provided by (Responsible Party):
Paul F. Siami, MD, Siami, Paul F., M.D.
ClinicalTrials.gov Identifier:
NCT00939120
First received: June 12, 2009
Last updated: April 15, 2015
Last verified: April 2015
  Purpose

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).


Condition Intervention Phase
Benign Prostatic Hyperplasia (BPH)
Drug: Tolterodine ER 4mg
Drug: Placebo
Drug: Pre-randomization Dutasteride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Siami, Paul F., M.D.:

Primary Outcome Measures:
  • Post-void Residual (PVR) Volume [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Urine Flow Rate (Qmax). [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Urine Voided Volume (Voiding) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Acute Urinary Retention (AUR) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overactive Bladder Questionnaire (OABq) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Patient Perception of Bladder Condition (PPBC) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • International Prostate Symptoms Score (IPSS), Total [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • International Prostate Symptoms Score, Voiding Subscore [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • International Prostate Symptoms Score (IPSS), Storage Subscore [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 46
Study Start Date: July 2009
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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: 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
Other Name: Placebo
Drug: Pre-randomization Dutasteride
All participants were on Dutasteride 0.5mg orally once daily prior to randomization.

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939120

Locations
United States, Indiana
Deaconess Clinic Gateway Health Center
Newburgh, Indiana, United States, 47630
Sponsors and Collaborators
Siami, Paul F., M.D.
GlaxoSmithKline
Pfizer
Investigators
Principal Investigator: Paul F Siami, MD Deaconess Clinic Research Institute
  More Information

No publications provided

Responsible Party: Paul F. Siami, MD, Medical Director, Deaconess Clinic Research Institute, Siami, Paul F., M.D.
ClinicalTrials.gov Identifier: NCT00939120     History of Changes
Other Study ID Numbers: 110983
Study First Received: June 12, 2009
Results First Received: March 16, 2015
Last Updated: April 15, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Siami, Paul F., M.D.:
Benign prostatic hyperplasia (BPH)
dutasteride
tolterodine ER

Additional relevant MeSH terms:
Hyperplasia
Lower Urinary Tract Symptoms
Prostatic Hyperplasia
Genital Diseases, Male
Pathologic Processes
Prostatic Diseases
Signs and Symptoms
Urological Manifestations
Dutasteride
Phenylpropanolamine
Tolterodine
5-alpha Reductase Inhibitors
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-Agonists
Anti-Obesity Agents
Appetite Depressants
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Nasal Decongestants
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 02, 2015