Benign Prostatic Hyperplasia, Prostatic Hyperplasia
Conditions
Keywords
placebo control, Chinese, Dutasteride, Randomized, Benign Prostatic Hyperplasia, Double blind
Brief summary
This randomized, double-blind, placebo-controlled, six-month parallel-group study assess efficacy and safety of dutasteride 0.5mg once daily in Chinese patients with Benign Prostatic Hyperplasia (BPH) , followed by a 12-month open-label treatment phase
Interventions
DRUGDutasteride 0.5mg capsule
Dutasteride 0.5mg once daily orally
DRUGDutasteride matched placebo
Dutasteride matched placebo once daily orally
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: * Clinical diagnosis of BPH * AUA-SI \>=12 \[American Urological Association Symptom Index\] * Qmax \> 5ml/sec and \<=15ml/sec and minimum voided volume of \>=125ml * Prostate volume \>=30cm(3) Exclusion: * Post void residual volume \>250ml * History or evidence of prostate cancer * Total serum PSA \<1.5ng/ml or \>10.0ng/ml (Prostate specific antigen) * Previous prostatic surgery or other invasive procedures to treat BPH. * History of AUR (Acute Urinary Retention) within 3 months * History of flexible/rigid cystoscopy or other instrumentation of the urethra within 7 days * Any causes other than BPH, which may in the judgement of the investigator, result in urinary symptoms or changes in flow rate * History of hepatic impairment or abnormal liver function tests * Use of any 5a-reductase inhibitors ,any drugs with antiandrogenic properties or other drugs noted for gynaecomastia effects, or could affect prostate volume, within past 6 months and throughout the study * Use of alpha-receptor blockers within 2 weeks and throughout the study. * Use of phytotherapy for BPH within 2 weeks and/or predicted to need phytotherapy during the study. * Concurrent use of anabolic steroids * Use of any alpha-adrenergic agonists or cholinergics within 48 hours prior to uroflowmetry assessment. * Hypersensitivity to any 5a-reductase inhibitor or other chemically-related drugs. * Actively trying to procreate or unwilling to wear a condom during intercourse with a woman of childbearing potential for duration of participation in this study and 16 weeks following treatment. * History or current evidence of drug or alcohol abuse within the previous 12 months. * History of any illness that in the opinion of the investigator might confound the results of the study or poses additional risk to the patient. * 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, of cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes or peptic ulcer disease which is uncontrolled by medical management. * History of renal insufficiency, or serum creatinine \>1.5xULN (Upper Limit of Normal ) * Participation in any investigational or marketed drug trial within 30 days and during the course of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in the Prostate Volume at Month 6 | Baseline and Month 6 | Percent change from baseline was calculated as the prostate volume at Month 6 minus the volume at baseline, divided by the prostate volume at baseline and multiplied by 100. Prostate volume was measured by transrectal ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Serum DHT at Month 3 | Baseline and Month 3 | Change from baseline was calculated as the value of DHT at Month 3 minus the baseline value. |
| Percent Change From Baseline in the Prostate Volume at Month 3 | Baseline and Month 3 | Percent change from baseline was calculated as the prostate volume at Month 3 minus the volume at baseline, divided by the prostate volume at baseline and multiplied by 100. Prostate volume was measured by transrectal ultrasound. |
| Change From Baseline in the Prostate Volume at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the prostate volume at Month 6 minus the volume at baseline. Prostate volume was measured by transrectal ultrasound. |
| Change From Baseline in the Prostate Volume at Month 3 | Baseline and Month 3 | Change from baseline was calculated as the prostate volume at Month 3 minus the volume at baseline. Prostate volume is measured by transrectal ultrasound. |
| Percent Change From Baseline in the Serum Dihydrotestosterone (DHT) at Month 6 | Baseline and Month 6 | Percent change from baseline was calculated as serum DHT at month 6 minus the value at baseline ,divided by the baseline value and multiplied by 100. |
| Percent Change From Baseline in the Serum DHT at Month 3 | Baseline and Month 3 | Percent change from baseline was calculated as the DHT at Month 3 minus the value at baseline, divided by the baseline value and multiplied by 100. |
| Percent Change From Baseline in the American Urological Association Symptom Index (AUA-SI) Score at Month 6 | Baseline and Month 6 | Percent change from baseline is calculated as the AUA-SI score at month 6 minus the baseline AUA-SI score, divided by the baseline score and multiplied by 100. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35. |
| Change From Baseline in the Serum DHT at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the value of DHT at Month 6 minus the baseline value. |
| Change From Baseline in the AUA-SI Score at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the AUS-SI score at month 6 minus the baseline score. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35. |
| Change From Baseline in the AUA-SI Score at Month 3 | Baseline and Month 3 | Change from baseline was calculated as the AUA-SI score at month 3 minus the baseline score. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostate hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35. |
| Percent Change From Baseline in Maximum Urinary Flow Rate (Qmax) at Month 6 | Baseline and Month 6 | Percent change from baseline was calculated as Qmax at Month 6 minus Qmax at baseline, divided by baseline Qmax and multiplied by 100. Qmax is the peak urinary flow measured by a uroflow meter. |
| Percent Change From Baseline in Qmax at Month 3 | Baseline and Month 3 | Percent change from baseline was calculated as Qmax at Month 3 minus Qmax at baseline, divided by baseline Qmax and multiplied by 100. Qmax is the peak urinary flow measured by a uroflow meter. |
| Change From Baseline in Qmax at Month 6 | Baseline and Month 6 | Change from baseline was calculated as Qmax at Month 6 minus Qmax at baseline. Qmax is the peak urinary flow measured by a uroflow meter. |
| Change From Baseline in Qmax at Month 3 | Baseline and Month 3 | Change from baseline was calculated as Qmax at Month 3 minus Qmax at baseline. Qmax is the peak urinary flow measured by a uroflow meter. |
| Percent Change From Baseline in the AUA-SI Score at Month 3 | Baseline and Month 3 | Percent change from baseline is calculated as the AUA-SI score at month 3 minus the baseline AUA-SI score, divided by the baseline score and multiplied by 100. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dutasteride 0.5 mg Oral dutasteride 0.5 milligrams (mg) once a day for 6 months | 126 |
| Placebo Matching oral placebo once a day for 6 months | 127 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | Dutasteride 0.5 mg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 65.8 years STANDARD_DEVIATION 7.7 | 66.9 years STANDARD_DEVIATION 8.2 | 66.4 years STANDARD_DEVIATION 7.9 |
| Race/Ethnicity, Customized Chinese | 126 participants | 127 participants | 253 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 126 Participants | 127 Participants | 253 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 126 | 25 / 127 |
| serious Total, serious adverse events | 0 / 126 | 1 / 127 |
Outcome results
Primary
Percent Change From Baseline in the Prostate Volume at Month 6
Percent change from baseline was calculated as the prostate volume at Month 6 minus the volume at baseline, divided by the prostate volume at baseline and multiplied by 100. Prostate volume was measured by transrectal ultrasound.
Time frame: Baseline and Month 6
Population: Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment (after the 4-week placebo run-in) and received at least one dose of study treatment. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the Prostate Volume at Month 6 | -17.00 percent change in volume | Standard Deviation 21.41 |
| Placebo | Percent Change From Baseline in the Prostate Volume at Month 6 | -2.77 percent change in volume | Standard Deviation 24.96 |
p-value: <0.000195% CI: [-20.23, -8.22]t-test, 2 sided
Secondary
Change From Baseline in Qmax at Month 3
Change from baseline was calculated as Qmax at Month 3 minus Qmax at baseline. Qmax is the peak urinary flow measured by a uroflow meter.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in Qmax at Month 3 | 0.93 ml/s | Standard Deviation 4.74 |
| Placebo | Change From Baseline in Qmax at Month 3 | 0.17 ml/s | Standard Deviation 4.56 |
Secondary
Change From Baseline in Qmax at Month 6
Change from baseline was calculated as Qmax at Month 6 minus Qmax at baseline. Qmax is the peak urinary flow measured by a uroflow meter.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in Qmax at Month 6 | 0.75 milliliters/second (ml/s) | Standard Deviation 5.61 |
| Placebo | Change From Baseline in Qmax at Month 6 | 0.03 milliliters/second (ml/s) | Standard Deviation 5.35 |
Secondary
Change From Baseline in the AUA-SI Score at Month 3
Change from baseline was calculated as the AUA-SI score at month 3 minus the baseline score. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostate hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the AUA-SI Score at Month 3 | -2.9 points on a scale | Standard Deviation 3.9 |
| Placebo | Change From Baseline in the AUA-SI Score at Month 3 | -2.4 points on a scale | Standard Deviation 3.9 |
Secondary
Change From Baseline in the AUA-SI Score at Month 6
Change from baseline was calculated as the AUS-SI score at month 6 minus the baseline score. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the AUA-SI Score at Month 6 | -4.9 points on a scale | Standard Deviation 4.8 |
| Placebo | Change From Baseline in the AUA-SI Score at Month 6 | -4.1 points on a scale | Standard Deviation 5.4 |
Secondary
Change From Baseline in the Prostate Volume at Month 3
Change from baseline was calculated as the prostate volume at Month 3 minus the volume at baseline. Prostate volume is measured by transrectal ultrasound.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the Prostate Volume at Month 3 | -7.11 cubic centimeters | Standard Deviation 13.02 |
| Placebo | Change From Baseline in the Prostate Volume at Month 3 | -1.06 cubic centimeters | Standard Deviation 11.48 |
Secondary
Change From Baseline in the Prostate Volume at Month 6
Change from baseline was calculated as the prostate volume at Month 6 minus the volume at baseline. Prostate volume was measured by transrectal ultrasound.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the Prostate Volume at Month 6 | -9.16 cubic centimeters | Standard Deviation 12.74 |
| Placebo | Change From Baseline in the Prostate Volume at Month 6 | -1.20 cubic centimeters | Standard Deviation 12.77 |
Secondary
Change From Baseline in the Serum DHT at Month 3
Change from baseline was calculated as the value of DHT at Month 3 minus the baseline value.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the Serum DHT at Month 3 | -319.605 pg/ml | Standard Deviation 256.058 |
| Placebo | Change From Baseline in the Serum DHT at Month 3 | -34.400 pg/ml | Standard Deviation 399.633 |
Secondary
Change From Baseline in the Serum DHT at Month 6
Change from baseline was calculated as the value of DHT at Month 6 minus the baseline value.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Change From Baseline in the Serum DHT at Month 6 | -289.175 picograms/milliliter (pg/ml) | Standard Deviation 270.61 |
| Placebo | Change From Baseline in the Serum DHT at Month 6 | -46.099 picograms/milliliter (pg/ml) | Standard Deviation 399.806 |
Secondary
Percent Change From Baseline in Maximum Urinary Flow Rate (Qmax) at Month 6
Percent change from baseline was calculated as Qmax at Month 6 minus Qmax at baseline, divided by baseline Qmax and multiplied by 100. Qmax is the peak urinary flow measured by a uroflow meter.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in Maximum Urinary Flow Rate (Qmax) at Month 6 | 16.14 percent change | Standard Deviation 57.43 |
| Placebo | Percent Change From Baseline in Maximum Urinary Flow Rate (Qmax) at Month 6 | 6.31 percent change | Standard Deviation 47.55 |
Secondary
Percent Change From Baseline in Qmax at Month 3
Percent change from baseline was calculated as Qmax at Month 3 minus Qmax at baseline, divided by baseline Qmax and multiplied by 100. Qmax is the peak urinary flow measured by a uroflow meter.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in Qmax at Month 3 | 14.34 percent change | Standard Deviation 42.86 |
| Placebo | Percent Change From Baseline in Qmax at Month 3 | 5.85 percent change | Standard Deviation 34.69 |
Secondary
Percent Change From Baseline in the American Urological Association Symptom Index (AUA-SI) Score at Month 6
Percent change from baseline is calculated as the AUA-SI score at month 6 minus the baseline AUA-SI score, divided by the baseline score and multiplied by 100. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the American Urological Association Symptom Index (AUA-SI) Score at Month 6 | -26.48 percent change | Standard Deviation 26.01 |
| Placebo | Percent Change From Baseline in the American Urological Association Symptom Index (AUA-SI) Score at Month 6 | -20.79 percent change | Standard Deviation 30.18 |
Secondary
Percent Change From Baseline in the AUA-SI Score at Month 3
Percent change from baseline is calculated as the AUA-SI score at month 3 minus the baseline AUA-SI score, divided by the baseline score and multiplied by 100. AUA-SI is a self-administered questionnaire that assesses the severity of benign prostatic hyperplasia symptoms. Scores range from 0 to 35; mild, 0-7; moderate, 8-19; severe, 20-35.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the AUA-SI Score at Month 3 | -15.64 percent change | Standard Deviation 24.59 |
| Placebo | Percent Change From Baseline in the AUA-SI Score at Month 3 | -11.91 percent change | Standard Deviation 21.55 |
Secondary
Percent Change From Baseline in the Prostate Volume at Month 3
Percent change from baseline was calculated as the prostate volume at Month 3 minus the volume at baseline, divided by the prostate volume at baseline and multiplied by 100. Prostate volume was measured by transrectal ultrasound.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the Prostate Volume at Month 3 | -12.02 percent change in volume | Standard Deviation 23.22 |
| Placebo | Percent Change From Baseline in the Prostate Volume at Month 3 | -1.02 percent change in volume | Standard Deviation 25.79 |
Secondary
Percent Change From Baseline in the Serum DHT at Month 3
Percent change from baseline was calculated as the DHT at Month 3 minus the value at baseline, divided by the baseline value and multiplied by 100.
Time frame: Baseline and Month 3
Population: ITT Population. Some participants were missing Month 3 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the Serum DHT at Month 3 | -59.15 percent change | Standard Deviation 37.9 |
| Placebo | Percent Change From Baseline in the Serum DHT at Month 3 | 28.33 percent change | Standard Deviation 133.71 |
Secondary
Percent Change From Baseline in the Serum Dihydrotestosterone (DHT) at Month 6
Percent change from baseline was calculated as serum DHT at month 6 minus the value at baseline ,divided by the baseline value and multiplied by 100.
Time frame: Baseline and Month 6
Population: ITT Population. Some participants were missing Month 6 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride 0.5 mg | Percent Change From Baseline in the Serum Dihydrotestosterone (DHT) at Month 6 | -52.53 percent change | Standard Deviation 44.42 |
| Placebo | Percent Change From Baseline in the Serum Dihydrotestosterone (DHT) at Month 6 | 26.78 percent change | Standard Deviation 149.07 |