Last updated: 11/04/2018 04:48:36
Benign Prostatic Hyperplasia Trial With dutasteride And tamsulosin Combination Treatment
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomized, double-blind, parallel group study to investigate the efficacy and safety of treatment with dutasteride (0.5mg) and tamsulosin (0.4mg), administered once daily for 4 years, alone and combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic benign prostatic hyperplasia
Trial description: This study will investigate the efficacy and safety of treatment with dutasteride and tamsulosin, administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic Benign Prostatic Hyperplasia (BPH). Study visits are every 3 months for up to 4 years (18 clinic visits). Transrectal ultrasound (TRUS) is done annually.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of events of acute urinary retention (AUR) or benign prostatic hyperplasia (BPH)-related prostatic surgery at the indicated time periods.
Timeframe: Years 1, 2, 3, and 4
Number of participants with AUR or BPH-related Surgery
Timeframe: Baseline (Day 1) through Year 4
Secondary outcomes:
Number of events of first BPH clinical progression at Years 1, 2, 3 and 4
Timeframe: Years 1, 2, 3, and 4
The number of participants with each of the five components of BPH clinical progression
Timeframe: Baseline (Day 1) to Year 4
Number of events of symptom deterioration at the indicated time periods
Timeframe: Years 1, 2, 3, and 4 (from treatment start until each participant's last treatment-phase visit)
Number of participants with an event of post-baseline BPH-related Macroscopic Hematuria
Timeframe: Baseline (Day 1) through Year 4
Number of participants with an event of post-baseline BPH-related Hematospermia
Timeframe: Baseline (Day 1) through Year 4
Adjusted mean change from baseline in International Prostate Symptom Score (IPSS) at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, and 48
Adjusted mean change from baseline in urinary flow rate (Qmax) at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, and 48
Adjusted mean percent change from baseline in prostate volume at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, and 48
Adjusted mean change from baseline in transition zone (portion of the prostate that surrounds the proximal urethra) volume at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, and 48
Number of unscheduled visits to GP/Urologist regarding AUR symptoms since the last study visit
Timeframe: Every 3 months from Month 3 to Month 48
Number of "Yes" responses to the question: "Would the participant have paid a visit to his GP/Urologist regarding AUR symptoms if the study visit had not been planned"?.
Timeframe: Every 3 months from Month 3 to Month 48
Number of visits to GP/Urologist regarding BPH-related surgery since the last study visit
Timeframe: Every 3 months from Month 3 to Month 48
Number of "Yes" responses to the question: "Would the participant have paid a visit to his GP/Urologist regarding BPH-related surgery since the last study visit?"
Timeframe: Every 3 months from Month 3 to Month 48
Number of unplanned visits to GP/Urologist that would have taken place if a scheduled study visit had not been planned (including visits resulting from UTI, UI, macroscopic haematuria, etc.)
Timeframe: Every 3 months from Month 3 to Month 48
Number of unscheduled visits to GP/Urologist (outpatient) planned, not relating to the study (including visits resulting from UTI, UI, macroscopic haematuria, etc.)
Timeframe: Every 3 months from Month 3 to Month 48
Adjusted mean change from baseline in BPH Impact Index (BII) at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, and 48
Adjusted mean change from baseline in BPH-Related Health Status (BHS) at Months 12, 24, 36, and 48
Timeframe: Baseline and Months 12, 24, 36, 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 1 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 2 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 3 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 4 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 5 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 6 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 7 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 8 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 9 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 10 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 11 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Patient Perception of Study Medication (PPSM): Number of Participants with the Indicated Responses to Question 12 (LOCF)
Timeframe: Baseline and Months 12, 24, 36, and 48
Interventions:
Enrollment:
4844
Primary completion date:
2009-11-05
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Antoñanzasa F, Brenesb F, Moleroc JM, Fernández-Prod A, Huertae A, Palenciae R, Cozarf JM. Cost-effectiveness of the combination therapy of dutasteride and tamsulosin in the treatment of benign prostatic hyperlasia in Spain. Actas Urol Esp. 2011;35(2):65–71.
Barkin J, Roehrborn CG, Siami P, et al. Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign hyperplasia: 2-year data from the CombAT trial. BJU Int 2009.
Bjerklund Johansen TE, Black L, Baker T. Cost-effectiveness of combination therapy for treatment of benign prostatic hyperplasia: A modeling based on the findings of CombAT. BJU Int. 2012;109(5):731–738.
Bjerklund Johansen TE, Black L, Baker T. Cost-effectiveness of combination therapy for treatment of benign prostatic hyperplasia: A modeling based on the findings of CombAT. BJU Int. Sep 20, 2011 Epub ahead of print.
Black L, Grove A, Morrill B. The psychometric validation of a US English satisfaction measure in patients with BPH. Health Qual Life Outcomes. 2009;7:55.
Byung-Ha Chung, Claus Roehrborn, Paul Siami, Kim Major-Walker, Betsy Morrill, Tim Wilson, Francesco Montorsi on behalf of the CombAT Study Group. Efficacy and safety of dutasteride, tamsulosin, and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate to severe BPH . Prostate Cancer Prostatic Dis. 2009;12(2):152-9.
C Roehrborn, P Siami, J Barkin, R Damião, K Major-Walker, I Nandy, B Morrill, P Gagnier, F Montorsi. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4 year results from the Combination of Avodart and Tamsulosin (CombAT) study. Eur Urol. 2010;57:123-131.
Chung B-H, Roehrborn CG, Siami P, et al. Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH. Prostate Cancer Prostatic Dis 2008.
Claus G. Roehrborn, Gerald L. Andriole, Tim Wilson, Ramiro Castro and Roger S. Rittmaster. Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the Combination of Avodart and Tamsulosin (CombAT) trial. Eur Urol 2010. 4 Nov doi:10.1016/j.eururo.2010.10.040 Epub ahead of print.
Claus G. Roehrborn, Gerald L. Andriole, Tim Wilson, Ramiro Castro and Roger S. Rittmaster. Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the Combination of Avodart and Tamsulosin (CombAT) trial. Eur Urol. 2011;59(2):244-9.
Claus G. Roehrborn, Jack Barkin, Paul Siami, Andrea Tubaro, Tim H. Wilson, Betsy B. Morrill and R. Paul Gagnier. Clinical outcomes after combination therapy with dutasteride and tamsulosin in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomised, double-blind CombAT trial. BJU Int. 2011;107(6):946-954.
Claus G. Roehrborn, Tim Wilson, Libby Black. Quantifying the Contribution of Symptom Improvement to Satisfaction of Men With Moderate to Severe Benign Prostatic Hyperplasia: 4-Year Data From the CombAT Trial. J Urol. 2012;187(5):1732-1738.
Edgardo Becher, Claus Roehrborn, Paul Siami, R. Paul Gagnier, Timothy H. Wilson and Francesco Montorsi . Effect of dutasteride and tamsulosin and the combination on storage and voiding symptoms/different symptom domains in men with moderate to severe BPH: 2-year results from the CombAT trial . Prostate Cancer Prostatic Dis. 2009;(12):369-374.
Francesco Montorsi, Claus Roehrborn, Javier Penit, Michael Borre, Ton A Roeleveld, Jean-Charles Alimi, Paul Gagnier, Timothy H Wilson. The effects of dutasteride and tamsulosin alone and in combination on storage and voiding symptoms in men with symptomatic benign prostatic hyperplasia: 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study . BJU Int. 2011;107(9):1426-31.
Francesco Montorsi, Thomas Henkel, Arno Geboers, Vincenzo Mirone, Peio Arrosagarai, Betsy Morrill, Libby Black. Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 4-year data from the CombAT study. Int J Clinc Prac. 2010;64(8):1042-1051.
Jack Barkin, Claus G. Roehrborn, Paul Siami, Olivier Haillot, Betsy Morrill, Libby Black and Francesco Montorsi. Effect of dutasteride, tamsulosin and the combination on patient quality of life and expectations and satisfaction with treatment in men with moderate-to-severe BPH: 2-year data from the CombAT trial. BJU Int. 2009;103(7):919-26.
Oliver Haillot, Avelino Fraga, Piotr Maciukiewicz, Dmitry Pushkar, Teuvo Tammela, Klaus Höfner, Venancio Chantada, Paul Gagnier, Betsy Morrill. The effects of combination therapy with dutasteride plus tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year post hoc analysis of European men in the CombAT study. Prostate Cancer Prostatic Dis. 2011;14(4):302-6.
Roehrborn CG, Siami P, Barkin J, Damião R, Montorsi F on behalf of the CombAT Study Group. The effects of dutasteride, tamsulosin, and combination therapy on lower urinary tract symptoms in men with prostatic enlargement: Two-year results from the Combination of Avodart and Tamsulosin (CombAT) study. J Urol. 2008 Feb;179(2):616-21.
Kruep EJ, Goodwin BB, Chaudhari S. Evaluation of Recent Trends in Treatment Patterns Among Men with Benign Prostatic Hyperplasia. Am J Mens Health.2013;7(3):214-219.
Medical condition
Prostatic Hyperplasia
Product
dutasteride
Collaborators
Not applicable
Study date(s)
November 2003 to May 2009
Type
Interventional
Phase
3
Participation criteria
Sex
Male
Age
50+ years
Accepts healthy volunteers
No
- Inclusion criteria:
- A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion criteria:
- A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
- males, aged ≥50 years
- clinical diagnosis of BPH by medical history and physical examination, including a digital rectal examination (DRE)
- International Prostate Symptom Score (IPSS) ≥12 points at Screening
- prostate volume ≥30 cc by transrectal ultrasonography; (TRUS)
- total serum Prostate Specific Antigen (PSA) ≥1.5ng/mL at Screening
- maximum flow rate (Qmax) >5 mL/sec and ≤15 mL/sec and minimum voided volume of ≥125 mL at Screening (based on two voids)
- willing and able to give written informed consent and comply with study procedures
- fluent and literate in local language with the ability to read, comprehend and record information on the IPSS, BII and Patient Perception of Study Medication
- able to swallow and retain oral medication
- willing and able to participate in the study for the full 4 years. Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- total serum PSA >10.0ng/mL at Screening
- history or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious DRE). Patients with suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6 months and stable PSA are eligible for the study. Note: If total serum PSA is >4ng/mL and unless PSA value has been stable for at least the past 2 years, the investigator should make every appropriate effort to exclude the possibility of prostate cancer, e.g. further DRE, review TRUS taken within previous month, consider 8-12 core prostate biopsy in accordance with routine clinical practice.
- previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and stent replacement) or other invasive procedures to treat BPH.
- history of flexible/rigid cystoscopy or other instrumentation of the urethra within 7 days prior to the Screening Visit. Routine catheterisation is acceptable with no time restriction.
- history of AUR within 3 months prior to Screening Visit.
- post-void residual volume >250mL (suprapubic ultrasound) at Screening.
- any causes other than BPH, which may in the judgement of the investigator, result in urinary symptoms or changes in flow rate (e.g. neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, or acute or chronic urinary tract infections).
- history of breast cancer or clinical breast examination finding of unclear origin or suggestive of malignancy.
- use of any 5-alpha-reductase inhibitor (e.g. Proscar®, Propecia®, Avodart®), any drugs with antiandrogenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, metronidazole, progestational agents), or other drugs which affect prostate volume, within past 6 months of the Screening Visit and throughout the study (other than as study medication).
- concurrent use of anabolic steroids
- use of phytotherapy for BPH within 2 weeks of Screening Visit and/or predicted to need phytotherapy during the study.
- use of any alpha-adrenoreceptor blockers (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin) within 2 weeks of Screening Visit and/or predicted to need any alpha blockers other than tamsulosin during the study. Note: the purpose of this criteria is to be able to standardise baseline symptom severity for all enrolled patients prior to randomisation and not to specifically exclude current alpha-adrenoreceptor blocker users from participation in the study.
- use of any alpha-adrenoreceptor agonists (e.g. pseudoephedrine, phenylephrine, ephedrine) or anticholinergics (e.g. oxybutynin, propantheline) or cholinergics (e.g. bethanecol chloride) within 48 hours prior to all uroflowmetry assessments.
- hypersensitivity to any alpha-/beta- adrenoreceptor blocker or 5-alpha-reductase inhibitor, or other chemically-related drugs.
- concurrent use of drugs known or thought to have an interaction with tamsulosin, e.g. cimetidine and warfarin.
- history of hepatic impairment or abnormal liver function tests at Screening defined as alanine aminotransferase (ALT), aspartate aminotranferase (AST), and/or alkaline phosphatase >2 times the upper limit of normal, or total bilirubin >1.5 times the upper limit of normal (unless associated with predominantly indirect bilirubin elevation or Gilbert's syndrome).
- history of renal insufficiency, or serum creatinine >1.5 times the upper limit of normal or serum creatinine ≥1.5 mg/dL at Screening.
- prior history of malignancies other than basal cell carcinoma or squamous cell carcinoma of the skin within the past 5 years. Subjects with a prior malignancy who have had no evidence of disease for at least the past 5 years are eligible.
- history of any illness that in the opinion of the investigator might confound the results of the study or poses additional risk to the patient.
- any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes or peptic ulcer disease which is uncontrolled by medical management.
- history of postural hypotension, dizziness, vertigo or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
- history of unsuccessful treatment with tamsulosin or 'first dose' hypotensive episode on initiation of alpha-1-adrenoreceptor antagonist therapy.
- history of unsuccessful treatment with finasteride or dutasteride
- history or current evidence of drug or alcohol abuse within the previous 12 months.
- participation in any investigational or marketed drug trial within 30 days (or 5 half-lives whichever is the longer) preceding the Screening Visit and/or during the course of this study.
Trial location(s)
Location
GSK Investigational Site
Greenbrae, California, United States, 94904
Status
Study Complete
Showing 1 - 6 of 490 Results
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2009-11-05
Actual study completion date
2009-11-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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