Prostatic Hyperplasia
Conditions
Keywords
Benign Prostatic Hyperplasia BPH dutasteride
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.
Interventions
DRUGDutasteride
once daily
DRUGPlacebo
once daily
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
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. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. | 181 |
| Dutasteride 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. | 184 |
| Total | 365 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 16 |
| Overall Study | Lack of Efficacy | 5 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 9 |
Baseline characteristics
| Characteristic | Placebo | Dutasteride | Total |
|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 6.76 | 68.0 years STANDARD_DEVIATION 6.07 | 67.4 years STANDARD_DEVIATION 6.44 |
| Race/Ethnicity, Customized Asian-Japanese | 181 participants | 184 participants | 365 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 181 Participants | 184 Participants | 365 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 116 / 184 | 124 / 193 |
| serious Total, serious adverse events | 8 / 184 | 20 / 193 |
Outcome results
Primary
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.
Time frame: Baseline and Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52 | -3.6 score on a scale | Standard Deviation 5.72 |
| Dutasteride | Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52 | -5.5 score on a scale | Standard Deviation 5.94 |
p-value: 0.00395% CI: [-2.7, -0.5]ANCOVA
Secondary
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.
Time frame: Baseline and Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52 | 0.6 milliliters per second (mL/sec) | Standard Deviation 3.82 |
| Dutasteride | Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52 | 2.2 milliliters per second (mL/sec) | Standard Deviation 4.89 |
Secondary
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.
Time frame: Baseline and Week 52
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=25% | 84 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=30% | 71 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=40% | 54 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=2 Points | 113 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=3 Points | 102 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=4 Points | 82 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=5 Points | 75 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=6 Points | 62 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=20% | 99 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=50% | 39 participants |
| Placebo | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=75% | 7 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=40% | 86 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=25% | 114 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=5 Points | 94 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=30% | 106 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=75% | 17 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=6 Points | 82 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=2 Points | 139 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=50% | 67 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=3 Points | 128 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=20% | 122 participants |
| Dutasteride | Number of Participants With IPSS Improvement From Baseline at Week 52 | Improvement >=4 Points | 115 participants |
Secondary
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
Time frame: Baseline and Week 52
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=1 mL/sec | 79 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=2 mL/sec | 56 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=2.5 mL/sec | 45 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=3 mL/sec | 44 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=4 mL/sec | 29 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=5 mL/sec | 22 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=10 mL/sec | 4 participants |
| Placebo | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=30% | 41 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=30% | 63 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=1 mL/sec | 103 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=4 mL/sec | 53 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=2 mL/sec | 86 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=10 mL/sec | 11 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=2.5 mL/sec | 73 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=5 mL/sec | 44 participants |
| Dutasteride | Number of Participants With Qmax Improvement From Baseline at Week 52 | Improvement >=3 mL/sec | 70 participants |
Secondary
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.
Time frame: Baseline and Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Prostate Volume at Week 52 | -8.9 cubic centimeters (cc) | Standard Deviation 18.76 |
| Dutasteride | Percent Change From Baseline in Prostate Volume at Week 52 | -31.5 cubic centimeters (cc) | Standard Deviation 16.85 |