This is an European double-blind, placebo controlled parallel group comparison of DUODART
(fixed dose combination of dutasteride 0. 5mg and tamsulosin 0. 4mg, one capsule daily) and
placebo.
PRIMARY OBJECTIVE:
To assess the change in sexual function from baseline to 1 year in sexually active men with
at least moderate BPH who are treated with DUODART, compared to men treated with placebo .
at least moderate BPH (international prostate symptom score - IPSS = or > 12) who are
treated with DUODART, compared to men treated with placebo . Change in sexual function will
be assessed by change in total score from the full men's sexual health questionnaire (MSHQ)
which has domains for erectile dysfunction, ejaculatory function and libido.
Inclusion Criteria:
- Males aged ≥50 years.
- Men must be sexually active. A man is considered sexually active if he has been
engaged in sexual activity with a partner during the past 4 weeks (at least once) and
plans to be active during the next 4 weeks (unless due to travel or other practical
reasons). Men should confirm that they are in a stable relationship and expect to
maintain their sexual activity over the next year.
- A confirmed clinical diagnosis of BPH.
- International Prostate Symptom Score (IPSS) ≥12 at Visit 1 (screening), with bother
score 4 or less (score from the IPSS Quality of Life question 8).
- Prostate volume ≥30 cc (by transrectal ultrasonography; TRUS). Measurement should be
available by the baseline visit and should have been made /arranged at the screening
visit or within the previous 6 months.
- Total serum prostate specific antigen (PSA ≥1. 5 ng/mL (see exclusion criteria 1) at
Visit 1 (screening).
- Willing and able to give signed written informed consent and comply with study
procedures, including the ability to participate in the study for the full 1 year (or
18 months if necessary because of a persistent sexual AE).
- Fluent and literate in local language with the ability to read, comprehend and record
information on the MSHQ, IPSS, PPSM, BPH Impact Index (BII) and C-SSRS
questionnaires.
- Able to swallow and retain oral medication.
- Men with a female partner of childbearing potential must either agree to use
effective contraception or have had a prior vasectomy. Contraception must be used
from 2 weeks prior to administration of the first dose of study treatment until at
least 5 half-lives for the drug (45 days) plus 3 months (i. e. a total of 4. 5 months)
to allow clearance of any altered sperm after the last dose of study treatment.
- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.
Exclusion Criteria:
- Total serum PSA >10. 0 ng/mL at Visit 1 (screening).
- History or evidence of prostate cancer (e. g. positive biopsy or ultrasound,
suspicious DRE and/or rising PSA). Subjects 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, including consideration of prostate biopsy.
Excluded medication and therapies
- Current or prior use (within the periods given) of the following prohibited
medications
- Any prior use of a 5α-reductase inhibitor (finasteride or dutasteride),
- Anti-cholinergics (e. g. oxybutynin, propantheline, tolerodine, solifenacin or
darifenacin) within 1 month prior to visit 2 (baseline)
- An alpha-adrenoreceptor blocker (i. e. indoramin, prazosin, terazosin, tamsulosin,
alfuzosin and doxazosin) within 1 month prior to visit 2 (baseline)
- Use of any drugs with anti-androgenic properties (e. g. spironolactone, flutamide,
bicalutamide, cimetidine, ketoconazole, progestational agents) within the 6 months
prior to visit 1 (screening).
- Use of any drugs noted for propensity to cause gynaecomastia, or which could affect
prostate volume, within 6 months prior to Visit 1 (screening).
- Use of any investigational or marketed study drug within 30 days or 5 half-lives of
the drug in question, (whichever is longer), preceding visit 2 (baseline).
- Current use (at the baseline visit or within the prior 1month) of:
- PDE-5 inhibitors for Erectile Dysfunction.
- Anabolic steroids.
- Drugs known or thought to have an interaction with tamsulosin, e. g. cimetidine and
warfarin.
- Use of phytotherapy for BPH within 2 weeks prior to Visit 1 (screening) and/or
predicted to need phytotherapy during the study.
- History of a known (immediate or delayed) hypersensitivity reaction or idiosyncratic
reaction to drugs chemically related to the study medication or excipients that, in
the opinion of the Investigator or GSK, contraindicate their participation.
- Previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and
stent replacement) or other invasive or minimally invasive procedures to treat BPH.
Recent Medical Procedures
- History of flexible/rigid cystoscopy or other instrumentation of the urethra within 7
days prior to Visit 1 (screening). Catheterisation (<10F) is acceptable with no time
restriction.
Medical history
- Presence of structural abnormalities in the Lower Urinary Tract or sexual organs
(e. g. urethral stricture, Peyronie's Disease etc) that may cause LUTS or sexual
dysfunction.
- History of AUR.
- Post-void residual volume >100 mL (suprapubic ultrasound) at Visit 1 (screening) or a
recorded PVR above this level on any previous examination. Measurement should be
available by the baseline visit and should have been made /arranged at the screening
visit or within the previous 6 months.
- Any causes other than BPH, which may in the judgement of the investigator, result in
urinary symptoms (e. g. neurogenic bladder, bladder neck contracture, urethral
stricture, bladder malignancy, acute or chronic prostatitis, or acute or chronic
urinary tract infections).
- History of 'first dose' hypotensive episode on initiation of alpha-1-adrenoreceptor
antagonist therapy.
- 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 breast cancer or clinical breast examination finding of unclear origin or
suggestive of malignancy.
- Prior history of malignancies (other than basal cell carcinoma or squamous cell
carcinoma of the skin) within the past 5 years. Subjects with an earlier history of
malignancy who have had no evidence of disease for at least the past 5 years are
eligible.
- History of hepatic impairment or abnormal liver function tests at Visit 1 (screening)
(defined as ALT, AST or alkaline phosphatase >2 times the ULN, or total bilirubin
>1. 5 times the ULN (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 at Visit 1 (screening).
- 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 the Screening visit; uncontrolled diabetes or peptic ulcer disease
which is uncontrolled by medical management.
- History or current evidence of drug or alcohol abuse within the previous 12 months.
- History or presence of any serious and/or unstable pre-existing psychiatric disorder
or other conditions that in the opinion of the Investigator or GSK Medical Monitor,
could interfere with subject's safety, obtaining informed consent, compliance to the
study procedures, or confound the results of the study.
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Garches 92380, France; Completed
GSK Investigational Site, Nantes cedex 2 44277, France; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Nîmes cedex 9 30029, France; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Orleans 45100, France; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Paris Cedex 13 75651, France; Completed
GSK Investigational Site, Thouars 79100, France; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Berlin 10787, Germany; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Berlin 14057, Germany; Terminated
GSK Investigational Site, Eisleben 06295, Germany; Completed
GSK Investigational Site, Argos 21200, Greece; Completed
GSK Investigational Site, Athens 115 22, Greece; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Athens 11521, Greece; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Athens 11522, Greece; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Athens 11527, Greece; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Larisa 41110, Greece; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Budapest 1032, Hungary; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Budapest 1074, Hungary; Terminated
GSK Investigational Site, Budapest 1204, Hungary; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Debrecen 4043, Hungary; Terminated
GSK Investigational Site, Miskolc 3526, Hungary; Completed
GSK Investigational Site, Nyíregyháza 4400, Hungary; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Szentes 6600, Hungary; Completed
GSK Investigational Site, Almere 1311RL, Netherlands; Completed
GSK Investigational Site, Beek 6191 JW, Netherlands; Completed
GSK Investigational Site, Doetinchem 7009 BL, Netherlands; Completed
GSK Investigational Site, EDE 6716 RP, Netherlands; Completed
GSK Investigational Site, Eindhoven 5623 EJ, Netherlands; Completed
GSK Investigational Site, Sneek 8601 ZK, Netherlands; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Utrecht 3511 NH, Netherlands; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Winterswijk 7101 BN, Netherlands; Completed
GSK Investigational Site, Alcazar de San Juan (Ciudad Real) 13600, Spain; Terminated
GSK Investigational Site, Barcelona 08006, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Bormujo (Sevilla) 41930, Spain; Terminated
GSK Investigational Site, Cadiz 11009, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Coslada 28822, Spain; Completed
GSK Investigational Site, Getafe/Madrid 28905, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Granada 18012, Spain; Completed
GSK Investigational Site, Guadalajara 19002, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Madrid 28040, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Madrid 28031, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Madrid 28007, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Marbella 29600, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Mendaro, Guipuzcoa 20850, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Murcia 30008, Spain; Terminated
GSK Investigational Site, Toledo 45004, Spain; Terminated
GSK Investigational Site, Vitoria- Gasteiz 01009, Spain; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Nuernberg, Bayern 90441, Germany; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Hagenow, Brandenburg 19230, Germany; Completed
GSK Investigational Site, Oranienburg, Brandenburg 16515, Germany; Completed
GSK Investigational Site, Strausberg, Brandenburg 15344, Germany; Terminated
GSK Investigational Site, Marburg, Hessen 35039, Germany; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Randwick, New South Wales 2031, Australia; Completed
GSK Investigational Site, Sydney, New South Wales 2000, Australia; Completed
GSK Investigational Site, Wahroonga, New South Wales 2076, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Buchholz, Niedersachsen 21244, Germany; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Aachen, Nordrhein-Westfalen 52064, Germany; Terminated
GSK Investigational Site, Dortmund, Nordrhein-Westfalen 44225, Germany; Terminated
GSK Investigational Site, Duelmen, Nordrhein-Westfalen 48249, Germany; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Herston, Queensland 4029, Australia; Completed
GSK Investigational Site, Kippa-Ring, Queensland 4021, Australia; Completed
GSK Investigational Site, Leipzig, Sachsen 04109, Germany; Terminated
GSK Investigational Site, Hettstedt, Sachsen-Anhalt 06333, Germany; Terminated
GSK Investigational Site, Kiel, Schleswig-Holstein 24143, Germany; Completed
GSK Investigational Site, Wedel, Schleswig-Holstein 22880, Germany; Terminated
GSK Investigational Site, Adelaide, South Australia 5000, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
GSK Investigational Site, Heidelberg, Victoria 3084, Australia; Completed
GSK Investigational Site, Malvern, Victoria 3144, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com
