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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00939120

Acronym

LUTS

Enrollment

Registered

2009-07-14

Start date

2009-07-31

Completion date

2014-09-30

Last updated

2015-05-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Benign Prostatic Hyperplasia (BPH)

Keywords

Benign prostatic hyperplasia (BPH), dutasteride, tolterodine ER

Brief summary

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).

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.

Interventions

DRUGTolterodine 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

DRUGPlacebo

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

DRUGPre-randomization Dutasteride

All participants were on Dutasteride 0.5mg orally once daily prior to randomization.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

50 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Post-void Residual (PVR) Volume	12 months	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).	12 months	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)	12 months	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)	12 months	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

Measure	Time frame	Description
Overactive Bladder Questionnaire (OABq)	12 months	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.
International Prostate Symptoms Score (IPSS), Storage Subscore	12 months	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.
Patient Perception of Bladder Condition (PPBC)	12 months	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	12 months	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	12 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Tolterodine ER 4mg + Dutasteride 0.5mg Patients randomized to experimental group received Dutasteride 0.5mg orally once daily plus Tolterodine ER 4mg orally once daily.	23
Placebo + Dutasteride 0.5mg Patients randomized to control group received Dutasteride 0.5mg orally once daily plus placebo orally once daily.	23
Total	46

Baseline characteristics

Characteristic	Placebo + Dutasteride 0.5mg	Tolterodine ER 4mg + Dutasteride 0.5mg	Total
Age, Continuous	67.7 years STANDARD_DEVIATION 7.4	68.6 years STANDARD_DEVIATION 9.5	68.2 years STANDARD_DEVIATION 8.4
International prostate symptoms score, storage subscore	8.7 units on a scale STANDARD_DEVIATION 2.2	8.9 units on a scale STANDARD_DEVIATION 2.7	8.8 units on a scale STANDARD_DEVIATION 2.4
International prostate symptoms score, total	17.7 units on a scale STANDARD_DEVIATION 4.5	18.0 units on a scale STANDARD_DEVIATION 6.2	17.9 units on a scale STANDARD_DEVIATION 5.4
International prostate symptoms score, voiding subscore	9.0 units on a scale STANDARD_DEVIATION 3.8	9.1 units on a scale STANDARD_DEVIATION 4.3	9.1 units on a scale STANDARD_DEVIATION 4
Maximum flow rate	12.4 mL/sec STANDARD_DEVIATION 4.8	11.1 mL/sec STANDARD_DEVIATION 3.5	11.7 mL/sec STANDARD_DEVIATION 4.2
Overactive bladder questionnaire	86.1 units on a scale STANDARD_DEVIATION 29.9	86.4 units on a scale STANDARD_DEVIATION 22.3	86.3 units on a scale STANDARD_DEVIATION 26.1
Patient's perception of bladder condition	3.7 units on a scale STANDARD_DEVIATION 1	3.7 units on a scale STANDARD_DEVIATION 0.9	3.7 units on a scale STANDARD_DEVIATION 0.9
Post-void residual volume	81.6 mL STANDARD_DEVIATION 60.7	93.0 mL STANDARD_DEVIATION 69.2	87.3 mL STANDARD_DEVIATION 64.6
Prostate specific antigen	5.3 ng/mL STANDARD_DEVIATION 8.8	4.0 ng/mL STANDARD_DEVIATION 2.1	4.6 ng/mL STANDARD_DEVIATION 6.4
Prostate volume	43.1 mL STANDARD_DEVIATION 16	43.9 mL STANDARD_DEVIATION 15.8	43.5 mL STANDARD_DEVIATION 15.7
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	22 Participants	23 Participants	45 Participants
Region of Enrollment United States	23 participants	23 participants	46 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	23 Participants	23 Participants	46 Participants
Urinary frequency	11.4 frequency episodes STANDARD_DEVIATION 2.2	11.3 frequency episodes STANDARD_DEVIATION 2.2	11.3 frequency episodes STANDARD_DEVIATION 2.2
Urinary urgency	8.6 urgency episodes STANDARD_DEVIATION 3.5	6.7 urgency episodes STANDARD_DEVIATION 3.5	7.7 urgency episodes STANDARD_DEVIATION 3.6
Voided volume	273.7 mL STANDARD_DEVIATION 189.9	202.5 mL STANDARD_DEVIATION 96.5	238.1 mL STANDARD_DEVIATION 153.2

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	21 / 23	22 / 23
serious Total, serious adverse events	4 / 23	5 / 23

Outcome results

Primary

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.

Time frame: 12 months