Dutasteride (GI198745) In Benign Prostatic Hyperplasia Subjects

Clinical Evaluation of Dutasteride in Benign Prostatic Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparative Study of GI198745 (Dutasteride) in Subjects With Benign Prostatic Hyperplasia.

This study will assess the efficacy and safety of GI198745 0.5mg given once daily for 52 weeks to Benign Prostatic Hyperplasia (BPH) patients.

Study Overview

• Status: Completed
• Conditions: Prostatic Hyperplasia
• Intervention / Treatment: Drug: Dutasteride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 263-0043
    • GSK Investigational Site
  • Chiba, Japan, 266-0031
    • GSK Investigational Site
  • Chiba, Japan, 272-0107
    • GSK Investigational Site
  • Fukuoka, Japan, 802-0077
    • GSK Investigational Site
  • Fukuoka, Japan, 810-0001
    • GSK Investigational Site
  • Fukuoka, Japan, 830-0027
    • GSK Investigational Site
  • Hyogo, Japan, 660-0052
    • GSK Investigational Site
  • Kanagawa, Japan, 215-0021
    • GSK Investigational Site
  • Kanagawa, Japan, 226-0025
    • GSK Investigational Site
  • Kanagawa, Japan, 229-1103
    • GSK Investigational Site
  • Kanagawa, Japan, 245-0015
    • GSK Investigational Site
  • Kanagawa, Japan, 252-0804
    • GSK Investigational Site
  • Kanagawa, Japan, 259-1132
    • GSK Investigational Site
  • Kyoto, Japan, 604-8436
    • GSK Investigational Site
  • Oita, Japan, 871-0012
    • GSK Investigational Site
  • Oita, Japan, 874-0937
    • GSK Investigational Site
  • Osaka, Japan, 542-0073
    • GSK Investigational Site
  • Osaka, Japan, 562-0036
    • GSK Investigational Site
  • Osaka, Japan, 584-0074
    • GSK Investigational Site
  • Tokyo, Japan, 130-0026
    • GSK Investigational Site
  • Tokyo, Japan, 131-0032
    • GSK Investigational Site
  • Tokyo, Japan, 150-0002
    • GSK Investigational Site
  • Tokyo, Japan, 152-0001
    • GSK Investigational Site
  • Tokyo, Japan, 153-0051
    • GSK Investigational Site
  • Tokyo, Japan, 183-0044
    • GSK Investigational Site
  • Tokyo, Japan, 186-0011
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Only subjects who meet all the following criteria during the screening phase will be enrolled in the study.

1. Diagnosis: BPH
2. Age: ≥50 years
3. Gender: Male
4. Estimated prostate volume ≥30cc (by TRUS)
5. I-PSS Symptom Score (total of 7 items) ≥8 points
6. Maximum flow rate (Qmax) ≤15mL/sec (voided volume measured simultaneously ≤150mL)*[1]

7. Patients who meet either of the following regarding tamsulosin HCl use:

   Patients with tamsulosin HCl use:

   Patients who have received tamsulosin HCl continuously for at least 4 weeks and who are likely to continue to take tamsulosin HCl without any change to the dosage and administration of the drug until the end of study treatment.

   Patients without tamsulosin HCl use:

   Patients who haven't received tamsulosin HCl in the past 4 weeks and who are unlikely to use tamsulosin HCl until the end of study treatment.

8. Outpatients
9. Patients who in person have given written consent

Exclusion Criteria:

Patients who apply to any of the following criteria during the screening phase will not be enrolled in the study.

1. Post void residual volume >250mL (by suprapubic ultrasound).
2. History of AUR within the previous 12 weeks.
3. Evidence or history of prostate cancer.
4. PSA >10ng/mL [in patients with PSA >4ng/mL, the presence of prostate cancer should be ruled out by the investigator/subinvestigator. DRE and free/total PSA ratio should be considered, and prostate biopsy be conducted if necessary].
5. Previous surgery (including balloon dilatation, thermotherapy and stent placement) or minimally invasive techniques for BPH.
6. Any causes other than BPH, which may in the judgment of the investigator/subinvestigator, affect evaluation of symptoms or urine flow (e.g., neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute/chronic prostatitis, acute/chronic urinary tract infection).
7. History of any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias*[2], congestive heart failure or cerebrovascular accident within the previous 6 months; or diabetes mellitus or peptic ulcer uncontrollable with medical treatment.
8. Liver function tests (AST, ALT, AL-P) >2 times the upper limit of normal.
9. Serum cleatinine >1.8mg/dL.
10. Use of any antiandrogen (e.g., chlormadinone acetate, allylesterenol) for BPH within the previous 12 months.
11. Use of a1-adrenoceptor blockers excluding tamsulosin HCl (e.g., prazosin HCl, urapidil slow-release capsule formulation, terazosin HCl, naftopidil), plant extract preparations for treatment of BPH (e.g., Eviprostat, cernitin pollen extract), herbal medicines (e.g., hachimi-jio-gan, gosha-jinki-gan), other drugs (e.g., Paraprost), and dietary or herbal supplements (e.g., saw palmetto) for relief of BPH symptoms within the previous 4 weeks.

Use of a-adrenoceptor agonists (e.g., pseudoephedrine, phenyle

• [1] Subjects with voided volume <150 mL at Qmax measurement cannot be enrolled in the study and may undergo re-measurement of Qmax before the visit for Week 0 for study entry.
• [2] Of "Degree II" according to "Grading of Side Effects (PMSB Notification No. 80 dated June 29, 1992) or equivalent (Appendix 4).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; once daily
Active Comparator: Dutasteride	Drug: Dutasteride; once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52	The International Prostate Symptom Score (I-PSS) consists of 7 verified questions concerning urinary symptoms and one quality of life question scored from 0 to 5(0=Not at All, to 5=Almost Always). The total score can range from 0 to 35. Score of 1-7=Mild, 8-19=Moderate, 20-35=Severe.	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Prostate Volume at Week 52	Prostate volume measurements by transrectal ultrasound (TRUS). Average prostate volume (55cc). The Ultrasound scans the prostate in the transverse plane while moving in the cephalocaudal direction of the prostate. The height and width of the prostate section with the greatest surface area is recorded.	Baseline and Week 52
Number of Participants With IPSS Improvement From Baseline at Week 52	Improvement is defined as greater than or equal to a 2 point increase in participants total score on the I-PSS questionaire.	Baseline and Week 52
Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52	Maximum Urine Flow Rate (Qmax) is the peak flow in milliliters per second.	Baseline and Week 52
Number of Participants With Qmax Improvement From Baseline at Week 52	Improvement was defined as an increase in Qmax by greater than or equal to 1 mL/sec	Baseline and Week 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-2042.2009.02357.x. Epub 2009 Aug 5.

Study record dates

Study Major Dates

• Study Start: February 17, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 6, 2007

Study Registration Dates

• First Submitted: August 24, 2006
• First Submitted That Met QC Criteria: August 24, 2006
• First Posted (Estimate): August 29, 2006

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Benign Prostatic Hyperplasia BPH dutasteride
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Dutasteride
• Other Study ID Numbers: ARI105326

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No