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

NCT02058368 | Completed Phase 3 Results

• 1 other identifier: 114265
• Study Type: interventional
• Target: 607
• Locations: 4 countries
• Sites: 46

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.

Conditions

Prostatic Hyperplasia

Keywords

Benign Prostatic Hyperplasia; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in International Prostate Symptom Score (IPSS) by Last Observation Carried Forward (LOCF) Approach at 24 Months

  IPSS (also called IPSS total score) is the sum of the seven questions with each score ranging from 0 (best) to 5 (worst). IPSS was self administered at screening, Baseline and each time-point of Month 3, 6, 9, 12, 15, 18, 21 and 24. Seven questions included are incomplete emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. The total IPSS score can range from 0-35 with severity catagories of mild (0 to 7), moderate (8 to 19) or severe (20 to 35). LOCF is defined as carrying forward the last non-missing post-Baseline assessment for participants with missing visit data and/or for participants who discontinued from the study. Baseline value is defined as the latest non-missing assessment of either treatment start date or randomization date. Month 24 is the primary timepoint and earlier timepoints are considered secondary. Change from Baseline defined as difference between Post-Baseline value and Baseline value.

  Baseline and 3, 6, 9, 12, 15, 18, 21 and 24 months

Secondary Outcomes (22)

• Percent Change in Prostate Volume From Baseline

  Baseline,12 and 24 months

• Number of Participants With IPSS Improvement From Baseline

  Baseline and 3, 6, 9,12,15,18,21 and 24 months

• Change From Baseline in Maximum Urine Flow Rate (Qmax) by LOCF Approach

  Baseline, 6, 12, 18 and 24 Months

• Number of Participants With Qmax Improvement From Baseline by LOCF Approach.

  Baseline 6, 12, 18 and 24 Months

• Number of Participants With Acute Urinary Retention (AUR) or Benign Prostatic Hyperplasia (BPH)-Related Prostatic Surgery

  Up to 24 Months

Study Arms (2)

Arm 1

EXPERIMENTAL

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; Drug: Dutasteride placebo capsules; Drug: Tamsulosin 0.2mg tablets; Drug: Disintegrating placebo tamsulosin tablet

Arm 2

EXPERIMENTAL

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; Drug: Tamsulosin 0.2mg tablets; Drug: Disintegrating placebo tamsulosin tablet

Interventions

Dutasteride 0.5mg capsules DRUG

Dutasteride 0.5mg capsules will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.

Arm 1

Dutasteride placebo capsules DRUG

Dutasteride placebo will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.

Arm 1; Arm 2

Tamsulosin 0.2mg tablets DRUG

Commercially available tamsulosin 0.2mg tablets will be supplied.

Arm 1; Arm 2

Disintegrating placebo tamsulosin tablet DRUG

Disintegrating placebo tamsulosin tablet will be supplied for the run-in period.

Arm 1; Arm 2

Eligibility Criteria

• Age: 50 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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.
• 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.
• 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
• History of breast cancer or clinical breast examination finding suggestive of malignancy.
• 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:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (46)

GSK Investigational Site

Xiame, Fujian, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510120, China

Location

GSK Investigational Site

Wuhan, Hubei, 430030, China

Location

GSK Investigational Site

Suzhou, Jiangsu, 215004, China

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GSK Investigational Site

Shenyang, Liaoning, China

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GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

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GSK Investigational Site

Beijing, 100020, China

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GSK Investigational Site

Beijing, 100191, China

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GSK Investigational Site

Beijing, 100730, China

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GSK Investigational Site

Chongqing, 400037, China

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GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200030, China

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GSK Investigational Site

Shanghai, 200032, China

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GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

GSK Investigational Site

Fukuoka, 810-0001, Japan

Location

GSK Investigational Site

Fukuoka, 811-0120, Japan

Location

GSK Investigational Site

Hyōgo, 651-1145, Japan

Location

GSK Investigational Site

Kanagawa, 226-0025, Japan

Location

GSK Investigational Site

Kanagawa, 252-0143, Japan

Location

GSK Investigational Site

Osaka, 530-0013, Japan

Location

GSK Investigational Site

Ōita, 874-0937, Japan

Location

GSK Investigational Site

Saitama, 343-0845, Japan

Location

GSK Investigational Site

Tokyo, 150-0002, Japan

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GSK Investigational Site

Tokyo, 184-0005, Japan

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GSK Investigational Site

Yamanashi, 400-0124, Japan

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GSK Investigational Site

Busan, 614-735, South Korea

Location

GSK Investigational Site

Daegu, 700-712, South Korea

Location

GSK Investigational Site

Gwangju, 501-757, South Korea

Location

GSK Investigational Site

Incheon, 405-760, South Korea

Location

GSK Investigational Site

Jeonju, 561-712, South Korea

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Seoul, 135-720, South Korea

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GSK Investigational Site

Seoul, 136-705, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Seoul, 150-713, South Korea

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GSK Investigational Site

Seoul, 156-707, South Korea

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GSK Investigational Site

Chiayi City, 613, Taiwan

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GSK Investigational Site

Hualien City, 970, Taiwan

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GSK Investigational Site

Kaohsiung City, Taiwan

Location

GSK Investigational Site

Kaohsiung Hsien, 83301, Taiwan

Location

GSK Investigational Site

New Taipei City, 23142, Taiwan

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GSK Investigational Site

Tainan, 704, Taiwan

Location

GSK Investigational Site

Tainan, 71004, Taiwan

Location

GSK Investigational Site

Tau-Yuan, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 30198102 BACKGROUND

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Prostatic Hyperplasia

Interventions

Dutasteride; Tamsulosin

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: February 10, 2014
• Study Start: February 10, 2014
• Primary Completion: March 3, 2017
• Study Completion: March 3, 2017
• Last Updated: April 5, 2019
• Results First Posted: April 5, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

KR (12); CN (15); JP (11); TW (8)