Trial record 7 of 73 for:    Open Studies | "Prostatic Hyperplasia"

Study to Compare the Efficacy and Safety of Combination Treatment With Dutasteride and Tamsulosin With Tamsulosin Monotherapy, in Men With Moderate to Severe Benign Prostatic Hyperplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02058368
First received: January 23, 2014
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

This is a multicentre, randomised, double-blind, parallel group study in Asian subjects. The aim of the study is to investigate whether combination therapy with dutasteride and tamsulosin is more effective than tamsulosin monotherapy for the improvement of symptoms and health outcomes in an at risk population of benign prostatic hyperplasia (BPH) clinical progression including older men (>=50 years), with moderate-severe symptoms of BPH, enlarged prostates (>=30 cubicentimeter [cc]) and prostate specific antigen (PSA) >= 1.5 nanograms per milliliter (ng/mL). Each subject who met the eligibility criteria at screening will enter a four-week single-blind, placebo run-in period following which each subject will be randomised into a 2 year double-blind treatment phase. The total study duration for each subject will be up to 110 weeks.


Condition Intervention Phase
Prostatic Hyperplasia
Drug: Dutasteride 0.5mg capsules
Drug: Dutasteride placebo capsules
Drug: Tamsulosin 0.2mg tablets
Drug: Disintegrating placebo tamsulosin tablet
Phase 3

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, Parallel Group Study to Compare the Efficacy and Safety of Combination Treatment With Dutasteride (0.5mg) and Tamsulosin (0.2mg) With Tamsulosin (0.2mg) Monotherapy, Administered Once Daily for 2 Years, on the Improvement of Symptoms and Health Outcomes in Men With Moderate to Severe Benign Prostatic Hyperplasia

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in the International Prostate Symptom Score (IPSS) at Year 2 [ Time Frame: Baseline to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    The IPSS is a 7-item questionnaire that measures urinary symptoms, but with an additional, independent eighth question on quality of life. It measures the level of urinary symptoms (including incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) reported as the total IPSS score. The first 7 items has a 6-point response scale (0=none/never to 5=almost always/5 or more times) with a total score that can range from 0-35: mild (0-7), moderate (8-19), or severe (20-35). The last item assesses quality of life reported as a Quality of Life assessment index.


Secondary Outcome Measures:
  • Percentage change from Baseline in Prostate Volume [ Time Frame: Baseline to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    Prostate volume was measured by transrectal ultrasound (TRUS). The prostate volume will be calculated using three prostate measurements (anteroposterior, cephalocaudal, and transverse diameters).

  • Proportion of subjects with IPSS improvement of >=2 points and >=3 points from baseline and, separately, >=25% improvement from Baseline [ Time Frame: Baseline to Year 2 (Week 104) ] [ Designated as safety issue: No ]
  • Change from Baseline in maximum urinary flow rate (Qmax) [ Time Frame: Baseline to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    Maximum urinary flow rate will be measured using an uroflow meter.

  • Proportion of subjects with Qmax improvement of >=3 milliliter per second (mL/sec) and, separately, >=30% improvement from baseline [ Time Frame: Baseline to Year 2 (Week 104) ] [ Designated as safety issue: No ]
  • Time to event/ proportion of subjects with acute urinary retention (AUR) or BPH related prostatic surgery [ Time Frame: Up to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    Time to first AUR or BPH-related surgical intervention will be defined as the number of days from date of first dose of randomized study drug to date of the first event (earliest occurring of either AUR or BPH-related surgery) for each subject.

  • Time to event/proportion of subjects with AUR [ Time Frame: Up to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    Time to first AUR -related surgical intervention will be defined as the number of days from date of first dose of randomized study drug to date of the first event (earliest occurring of either AUR related surgery) for each subject.

  • Time to event/proportion of subjects undergoing BPH related prostatic surgery [ Time Frame: Up to Year 2 (Week 104) ] [ Designated as safety issue: No ]
    Time to first BPH -related surgical intervention will be defined as the number of days from date of first dose of randomized study drug to date of the first event (earliest occurring of either BPH related surgery) for each subject.


Estimated Enrollment: 600
Study Start Date: February 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Run-in phase: All subjects qualifying for the study will entered into a placebo run-in phase will receive one soft gelatin placebo capsule (swallowed whole and not chewed) and one oral disintegrating placebo tablet once daily (OD) (dissolved on the tongue then swallowed not chewed), following the first meal each day for four weeks. Randomized treatment phase: Subjects will be instructed to take 1 dutasteride 0.5 milligram (mg) capsule (swallowed whole and not chewed) and one tamsulosin 0.2mg tablet OD (dissolved on the tongue then swallowed not chewed) following the first meal each day for 104 weeks.
Drug: Dutasteride 0.5mg capsules
Dutasteride 0.5mg capsules will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.
Drug: Dutasteride placebo capsules
Dutasteride placebo will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.
Drug: Tamsulosin 0.2mg tablets
Commercially available tamsulosin 0.2mg tablets will be supplied.
Drug: Disintegrating placebo tamsulosin tablet
Disintegrating placebo tamsulosin tablet will be supplied for the run-in period.
Experimental: Arm 2
Run-in phase: All subjects qualifying for the study will entered into a placebo run-in phase will receive one soft gelatine placebo capsule (swallowed whole and not chewed) and one oral disintegrating placebo tablet OD (dissolved on the tongue then swallowed not chewed), following the first meal each day for four weeks. Randomized treatment phase: Subjects will be instructed to take 1 placebo dutasteride 0.5mg capsule (swallowed whole and not chewed) and one tamsulosin 0.2mg tablet OD (dissolved on the tongue then swallowed not chewed) following the first meal each day for 104 weeks.
Drug: Dutasteride placebo capsules
Dutasteride placebo will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.
Drug: Tamsulosin 0.2mg tablets
Commercially available tamsulosin 0.2mg tablets will be supplied.
Drug: Disintegrating placebo tamsulosin tablet
Disintegrating placebo tamsulosin tablet will be supplied for the run-in period.

  Eligibility

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

Inclusion Criteria:

  • 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 >=30cc (by TRUS)
  • Total serum Prostate Specific Antigen (PSA) >=1.5ng/mL and <= 10 ng/mL at Screening
  • Maximum urinary flow rate (Qmax) >5mL/sec and 15mL/sec and minimum voided volume of >=125 milliliter (mL) at Screening
  • Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • Fluent and literate in local language with the ability to comprehend and record information on the IPSS, BPH-related Health Status (BHS), BPH Impact Index (BII), and Problem Assessment Scale Sexual Function Inventory (PAS- SFI) questionnaires
  • Men with a female partner of childbearing potential must agree to use a condom up to 6 months after the last dose (applies only to countries where the local product monograph for dutasteride mandates condom use for men with a female partner of childbearing potential)

Exclusion Criteria:

  • History or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious Digital Rectal Examination [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, including consideration of prostate biopsy.
  • Previous prostatic surgery (including TURP, laser, transrectal high intensity focused ultrasounds(HIFU), thermotherapy, transurethral needle ablation (TUNA), balloon dilatation, 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. Catheterisation (<10F) 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 conditions other than BPH, which may in the judgment 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).
  • Unstable liver disease (chronic stable hepatitis B and C are acceptable if subject meets entry criteria).
  • History of renal insufficiency, or serum creatinine >1.5 times the upper limit of normal at Screening.
  • Any unstable, serious co-existing medical condition(s) including, but not limited to:

    1. 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.
    2. 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.
    3. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to study procedures in the opinion of the investigator or GSK medical monitor. Investigator may consult with GSK Medical Monitor if condition could interfere with subject's safety
    4. History of breast cancer or clinical breast examination finding suggestive of malignancy.
    5. History of malignancy within the past five years, except for basal cell carcinoma of the skin. Subjects with a priori malignancy who have had no evidence of disease for at least the past 5 years are eligible.
  • Current or Previous Use of the following medications:

    1. Use of any 5-alpha-reductase inhibitor (e.g. finasteride), any drugs with antiandrogenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents), or other drugs noted for gynaecomastia effects, or that could affect prostate volume, within the 6 months preceding the historical TRUS or Screening Visit and throughout the study (other than as study medication). Previous use of dutasteride should not be within 6 months of the baseline or historical TRUS.
    2. Anabolic steroids (subject must discontinue for 6 months prior to study entry to be eligible) and agree not to take them for the duration of the study.
    3. Phytotherapy for BPH within 2 weeks of Screening Visit and/or predicted to need phytotherapy during the study.
    4. Use of any alpha-adrenoreceptor blockers within 2 weeks of Screening Visit (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin, doxazosin, silodosin) and/or predicted to need any alpha blockers other than the study prescribed tamsulosin.
    5. Use of any alpha-adrenoreceptor agonists (e.g. pseudoephedrine, phenylephedrine, ephedrine) or anticholinergics (e.g. oxybutynin,tolterodine, darifenacin, solifenacin,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.
  • Participation in any investigational or marketed drug trial within 30 days (or 5 half-lives of drug, whichever is the longer) preceding the Screening Visit and/or plans to participate in such a trial during the course of this 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: NCT02058368

Contacts
Contact: US GSK Clinical Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 46 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02058368     History of Changes
Other Study ID Numbers: 114265
Study First Received: January 23, 2014
Last Updated: August 21, 2014
Health Authority: Japan: Pharmaceutical and Medical Device Agency
South Korea: Ministry of Food and Drug Safety
China: Food and Drug Administration
Taiwan : Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Benign Prostatic Hyperplasia
Quality of Life

Additional relevant MeSH terms:
Prostatic Hyperplasia
Hyperplasia
Prostatic Diseases
Genital Diseases, Male
Pathologic Processes
Tamsulosin
Dutasteride
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses
5-alpha Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014