Dutasteride (GI198745) In Benign Prostatic Hyperplasia Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00368979
• Collaborator: (none)
• Enrollment: 378
• Locations: 26
• Arms: 2
• Duration (Months): 21.6
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia	Drug: Dutasteride; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 378 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: Feb 17, 2006
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 6, 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52 [Baseline and 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.

Secondary Outcome Measures

1. Percent Change From Baseline in Prostate Volume at Week 52 [Baseline and 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.

2. Number of Participants With IPSS Improvement From Baseline at Week 52 [Baseline and Week 52]

   Improvement is defined as greater than or equal to a 2 point increase in participants total score on the I-PSS questionaire.

3. Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52 [Baseline and Week 52]

   Maximum Urine Flow Rate (Qmax) is the peak flow in milliliters per second.

4. Number of Participants With Qmax Improvement From Baseline at Week 52 [Baseline and Week 52]

   Improvement was defined as an increase in Qmax by greater than or equal to 1 mL/sec

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

1. Outpatients

2. 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Chiba		Japan	263-0043
2	GSK Investigational Site	Chiba		Japan	266-0031
3	GSK Investigational Site	Chiba		Japan	272-0107
4	GSK Investigational Site	Fukuoka		Japan	802-0077
5	GSK Investigational Site	Fukuoka		Japan	810-0001
6	GSK Investigational Site	Fukuoka		Japan	830-0027
7	GSK Investigational Site	Hyogo		Japan	660-0052
8	GSK Investigational Site	Kanagawa		Japan	215-0021
9	GSK Investigational Site	Kanagawa		Japan	226-0025
10	GSK Investigational Site	Kanagawa		Japan	229-1103
11	GSK Investigational Site	Kanagawa		Japan	245-0015
12	GSK Investigational Site	Kanagawa		Japan	252-0804
13	GSK Investigational Site	Kanagawa		Japan	259-1132
14	GSK Investigational Site	Kyoto		Japan	604-8436
15	GSK Investigational Site	Oita		Japan	871-0012
16	GSK Investigational Site	Oita		Japan	874-0937
17	GSK Investigational Site	Osaka		Japan	542-0073
18	GSK Investigational Site	Osaka		Japan	562-0036
19	GSK Investigational Site	Osaka		Japan	584-0074
20	GSK Investigational Site	Tokyo		Japan	130-0026
21	GSK Investigational Site	Tokyo		Japan	131-0032
22	GSK Investigational Site	Tokyo		Japan	150-0002
23	GSK Investigational Site	Tokyo		Japan	152-0001
24	GSK Investigational Site	Tokyo		Japan	153-0051
25	GSK Investigational Site	Tokyo		Japan	183-0044
26	GSK Investigational Site	Tokyo		Japan	186-0011

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00368979
• Other Study ID Numbers: ARI105326
• First Posted: Aug 29, 2006
• Last Update Posted: Sep 26, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by GlaxoSmithKline: Benign Prostatic Hyperplasia BPH dutasteride
• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Dutasteride

Study Results

Participant Flow

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Period Title: Overall Study
STARTED	185	193
COMPLETED	160	163
NOT COMPLETED	25	30

Baseline Characteristics

Arm/Group Title	Placebo	Dutasteride	Total
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Total of all reporting groups
Overall Participants	181	184	365
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.9 (6.76)	68.0 (6.07)	67.4 (6.44)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	181 100%	184 100%	365 100%
Race/Ethnicity, Customized (participants) [Number]
Asian-Japanese	181 100%	184 100%	365 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52
Description	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.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Measure Participants	181	184
Mean (Standard Deviation) [score on a scale]	-3.6 (5.72)	-5.5 (5.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6
	Confidence Interval	() 95%; -2.7 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Prostate Volume at Week 52
Description	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.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Measure Participants	180	183
Mean (Standard Deviation) [cubic centimeters (cc)]	-8.9 (18.76)	-31.5 (16.85)

3. Secondary Outcome

Title	Number of Participants With IPSS Improvement From Baseline at Week 52
Description	Improvement is defined as greater than or equal to a 2 point increase in participants total score on the I-PSS questionaire.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Measure Participants	181	184
Improvement >=2 Points	113 62.4%	139 75.5%
Improvement >=3 Points	102 56.4%	128 69.6%
Improvement >=4 Points	82 45.3%	115 62.5%
Improvement >=5 Points	75 41.4%	94 51.1%
Improvement >=6 Points	62 34.3%	82 44.6%
Improvement >=20%	99 54.7%	122 66.3%
Improvement >=25%	84 46.4%	114 62%
Improvement >=30%	71 39.2%	106 57.6%
Improvement >=40%	54 29.8%	86 46.7%
Improvement >=50%	39 21.5%	67 36.4%
Improvement >=75%	7 3.9%	17 9.2%

4. Secondary Outcome

Title	Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52
Description	Maximum Urine Flow Rate (Qmax) is the peak flow in milliliters per second.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Measure Participants	181	184
Mean (Standard Deviation) [milliliters per second (mL/sec)]	0.6 (3.82)	2.2 (4.89)

5. Secondary Outcome

Title	Number of Participants With Qmax Improvement From Baseline at Week 52
Description	Improvement was defined as an increase in Qmax by greater than or equal to 1 mL/sec
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.	Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
Measure Participants	179	183
Improvement >=1 mL/sec	79 43.6%	103 56%
Improvement >=2 mL/sec	56 30.9%	86 46.7%
Improvement >=2.5 mL/sec	45 24.9%	73 39.7%
Improvement >=3 mL/sec	44 24.3%	70 38%
Improvement >=4 mL/sec	29 16%	53 28.8%
Improvement >=5 mL/sec	22 12.2%	44 23.9%
Improvement >=10 mL/sec	4 2.2%	11 6%
Improvement >=30%	41 22.7%	63 34.2%

Adverse Events

Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in all participants who received at least one dose of the investigational product.
Arm/Group Title	Placebo		Dutasteride
Arm/Group Description	Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.		Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments.
All Cause Mortality
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/184 (4.3%)		20/193 (10.4%)
Cardiac disorders
Acute myocardial infarction	0/184 (0%)		1/193 (0.5%)
Coronary artery stenosis	1/184 (0.5%)		0/193 (0%)
Eye disorders
Macular degeneration	0/184 (0%)		1/193 (0.5%)
Gastrointestinal disorders
Colonic polyp	0/184 (0%)		3/193 (1.6%)
Inguinal hernia	2/184 (1.1%)		0/193 (0%)
Enterocolitis	0/184 (0%)		1/193 (0.5%)
Haemorrhoids	1/184 (0.5%)		0/193 (0%)
Intestinal obstruction	0/184 (0%)		1/193 (0.5%)
Hepatobiliary disorders
Cholangitis	0/184 (0%)		1/193 (0.5%)
Infections and infestations
Pneumonia	0/184 (0%)		1/193 (0.5%)
Urinary tract infection	0/184 (0%)		1/193 (0.5%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/184 (0%)		1/193 (0.5%)
Lumbar spinal stenosis	1/184 (0.5%)		0/193 (0%)
Synovitis	0/184 (0%)		1/193 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/184 (0.5%)		1/193 (0.5%)
Bladder cancer	1/184 (0.5%)		0/193 (0%)
Lymph node cancer metastatic	0/184 (0%)		1/193 (0.5%)
Meningioma	0/184 (0%)		1/193 (0.5%)
Pancreatic carcinoma	0/184 (0%)		1/193 (0.5%)
Nervous system disorders
Cerebral infarction	2/184 (1.1%)		1/193 (0.5%)
Dementia Alzheimer's type	0/184 (0%)		1/193 (0.5%)
Thrombotic stroke	0/184 (0%)		1/193 (0.5%)
Vascular disorders
Aortic dissection	0/184 (0%)		1/193 (0.5%)
Microscopic polyangiitis	1/184 (0.5%)		0/193 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	116/184 (63%)		124/193 (64.2%)
Gastrointestinal disorders
Diarrhoea	16/184 (8.7%)		19/193 (9.8%)
Constipation	12/184 (6.5%)		13/193 (6.7%)
Gastritis	4/184 (2.2%)		10/193 (5.2%)
Infections and infestations
Nasopharyngitis	78/184 (42.4%)		80/193 (41.5%)
Musculoskeletal and connective tissue disorders
Back pain	14/184 (7.6%)		12/193 (6.2%)
Arthralgia	6/184 (3.3%)		10/193 (5.2%)
Nervous system disorders
Headache	11/184 (6%)		8/193 (4.1%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	14/184 (7.6%)		19/193 (9.8%)
Skin and subcutaneous tissue disorders
Eczema	8/184 (4.3%)		14/193 (7.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.