Clinical trial NCT02058368: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Hyperplasia
Keywords: Benign Prostatic Hyperplasia
Quality of Life
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-02-10
Enrollment: 607
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in International Prostate Symptom Score (IPSS) by Last Observation Carried Forward (LOCF) Approach at 24 Months
timeFrame: Baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months
Secondary outcomes:
measure: Percent Change in Prostate Volume From Baseline
timeFrame: Baseline,12 and 24 months
measure: Number of Participants With IPSS Improvement From Baseline
timeFrame: Baseline and 3, 6, 9,12,15,18,21 and 24 months
measure: Change From Baseline in Maximum Urine Flow Rate (Qmax) by LOCF Approach
timeFrame: Baseline, 6, 12, 18 and 24 Months
measure: Number of Participants With Qmax Improvement From Baseline by LOCF Approach.
timeFrame: Baseline 6, 12, 18 and 24 Months
measure: Number of Participants With Acute Urinary Retention (AUR) or Benign Prostatic Hyperplasia (BPH)-Related Prostatic Surgery
timeFrame: Up to 24 Months
measure: Number of Subjects With AUR
timeFrame: Up to 24 Months
measure: Number of Participants With BPH-related Surgery
timeFrame: Up to 24 Months
measure: Change From Baseline in the BPH-related Health Status (BHS) by LOCF Approach
timeFrame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 Months
measure: Change From Baseline in BPH Impact Index (BII) by LOCF Approach
timeFrame: Baseline 3, 6, 9, 12, 15, 18, 21 and 24 Months
measure: Change From Baseline in Problem Assessment Scale of the Sexual Function Inventory (PAS-SFI)
timeFrame: Baseline, 12 and 24 Months
measure: Number of Hospitalization Days
timeFrame: Up to 24 Months
measure: Number of Participants in a Hospital Ward
timeFrame: Up to 24 Months
measure: Number of Participants With Hospital Admissions
timeFrame: Up to 24 Months
measure: Number of Participants With Non-serious Adverse Events (AE) and Serious AE (SAE)
timeFrame: Up to 24 Months
measure: Change From Baseline in Serum Prostate Specific Antigen (PSA)
timeFrame: Baseline 6, 12 and 24 Months
measure: Number of Participants With Vital Signs Exceeding Threshold Values
timeFrame: Up to 24 Months
measure: Change From Baseline in Post Void Residual Volume
timeFrame: Baseline, 6, 12, 18 and 24 Months
measure: Number of Participants With Threshold Hematology Value.
timeFrame: Up to 24 Months
measure: Number of Participants With Threshold Clinical Chemistry Value.
timeFrame: Up to 24 Months
measure: Number of Participants With Digital Rectal Examination (DRE)
timeFrame: 6, 12, 18 , 24 months and final assessment
measure: Number of Participants With Clinically Significant Qualitative Breast Examination
timeFrame: 6, 12, 18 , 24 months and final assessment
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior
timeFrame: 6, 12, 18 , 24 months and final assessment
Other outcomes:
Locations:
city: Xiame
country: China
facility: GSK Investigational Site
state: Fujian
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Suzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Shenyang
country: China
facility: GSK Investigational Site
state: Liaoning
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Chonju
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Chia-Yi
country: Taiwan
facility: GSK Investigational Site
city: Hualien
country: Taiwan
facility: GSK Investigational Site
city: Kaohsiung Hsien
country: Taiwan
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: New Taipei City
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Tau-Yuan
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Haque N, Masumori N, Sakamoto S, Ye Z, Yoon SJ, Kuo HC, Brotherton B, Wilson T, Muganurmath C, McLaughlin M, Manyak M. Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of moderate-to-severe benign prostatic hyperplasia in Asian men. Int J Urol. 2018 Nov;25(11):944-951. doi: 10.1111/iju.13785. Epub 2018 Sep 9.