Year 1
(%) |
Years 2, 3 and 4*
(%) |
|||
---|---|---|---|---|
Finasteride | Placebo | Finasteride | Placebo | |
* Combined Years 2 to 4
N = 1524 and 1516, finasteride vs. placebo, respectively |
||||
Impotence
|
8.1
|
3.7
|
5.1
|
5.1
|
Decreased Libido
|
6.4
|
3.4
|
2.6
|
2.6
|
Decreased Volume of Ejaculate
|
3.7
|
0.8
|
1.5
|
0.5
|
Ejaculation Disorder
|
0.8
|
0.1
|
0.2
|
0.1
|
Breast Enlargement
|
0.5
|
0.1
|
1.8
|
1.1
|
Breast Tenderness
|
0.4
|
0.1
|
0.7
|
0.3
|
Rash
|
0.5
|
0.2
|
0.5
|
0.1
|
Adverse Experience | Placebo
(N=737) (%) |
Doxazosin
4 mg or 8 mg* (N=756) (%) |
Finasteride
(N=768) (%) |
Combination
(N=786) (%) |
---|---|---|---|---|
* Doxazosin dose was achieved by weekly titration (1 to 2 to 4 to 8 mg). The final tolerated dose (4 mg or 8 mg) was administered at end-Week 4. Only those patients tolerating at least 4 mg were kept on doxazosin. The majority of patients received the 8 mg dose over the duration of the study.
|
||||
Body as a whole
Asthenia Headache |
7.1 2.3 |
15.7 4.1 |
5.3 2 |
16.8 2.3 |
Cardiovascular
Hypotension Postural Hypotension |
0.7 8 |
3.4 16.7 |
1.2 9.1 |
1.5 17.8 |
Metabolic and Nutritional
Peripheral Edema |
0.9 |
2.6 |
1.3 |
3.3 |
Nervous
Dizziness Libido Decreased Somnolence |
8.1 5.7 1.5 |
17.7 7 3.7 |
7.4 10 1.7 |
23.2 11.6 3.1 |
Respiratory
Dyspnea Rhinitis |
0.7 0.5 |
2.1 1.3 |
0.7 1 |
1.9 2.4 |
Urogenital
Abnormal Ejaculation Gynecomastia Impotence Sexual Function Abnormal |
2.3 0.7 12.2 0.9 |
4.5 1.1 14.4 2 |
7.2 2.2 18.5 2.5 |
14.1 1.5 22.6 3.1 |
Mean (± SD) | |
---|---|
* Range
|
|
Bioavailability
|
63% (34 to 108%)*
|
Clearance (mL/min)
|
165 (55)
|
Volume of Distribution (L)
|
76 (14)
|
Half-Life (hours)
|
6.2 (2.1)
|
Mean (± SD) | ||
---|---|---|
45 to 60 years old (n=12) | ≥70 years old (n=12) | |
* First-dose values; all other parameters are last-dose values
|
||
AUC (ng•hr/mL)
|
389 (98)
|
463 (186)
|
Peak Concentration (ng/mL)
|
46.2 (8.7)
|
48.4 (14.7)
|
Time to Peak (hours)
|
1.8 (0.7)
|
1.8 (0.6)
|
Half-Life (hours)*
|
6 (1.5)
|
8.2 (2.5)
|
* Patients with multiple events may be counted more than once for each type of event
† Hazard ratio based on log rank test |
|||||
|
|
|
|
|
|
|
|
|
|
|
|
All Treatment Failures
|
37.1
|
26.2
|
0.68
|
(0.57 to 0.79)
|
<0.001
|
Surgical Interventions for BPH
|
10.1
|
4.6
|
0.45
|
(0.32 to 0.63)
|
<0.001
|
Acute Urinary Retention Requiring Catheterization
|
6.6
|
2.8
|
0.43
|
(0.28 to 0.66)
|
<0.001
|
Two consecutive symptom scores ≥20
|
9.2
|
6.7
|
|
||
Bladder Stone
|
0.4
|
0.5
|
|||
Incontinence
|
2.1
|
1.7
|
|||
Renal Failure
|
0.5
|
0.6
|
|||
UTI
|
5.7
|
4.9
|
|||
Discontinuation due to worsening of BPH, lack of improvement, or to receive other medical treatment
|
21.8
|
13.3
|
|
|
||||
|
|
|
|
|
|
AUA 4-point rise
Acute urinary retention Incontinence Recurrent UTI/urosepsis Creatinine rise Total Events |
100 (13.6)
18 (2.4) 8 (1.1) 2 (0.3) 0 (0) 128 (17.4) |
59 (7.8)
13 (1.7) 11 (1.5) 2 (0.3) 0 (0) 85 (11.2) |
74 (9.6)
6 (0.8) 9 (1.2) 0 (0) 0 (0) 89 (11.6) |
41 (5.2)
4 (0.5) 3 (0.4) 1 (0.1) 0 (0) 49 (6.2) |
274 (9)
41 (1.3) 31 (1) 5 (0.2) 0 (0) 351 (11.5) |
Placebo
N=534 |
Doxazosin
N=582 |
Finasteride
N=565 |
Combination
N=598 |
|
---|---|---|---|---|
Baseline Mean (SD)
|
16.8 (6)
|
17 (5.9)
|
17.1 (6)
|
16.8 (5.8)
|
Mean Change
AUA Symptom Score (SD) |
-4.9 (5.8)
|
-6.6 (6.1)
|
-5.6 (5.9)
|
-7.4 (6.3)
|
Comparison to
Placebo (95% CI) |
|
-1.8
(-2.5, -1.1) |
-0.7
(-1.4, 0) |
-2.5
(-3.2, -1.8) |
Comparison to
Doxazosin alone (95% CI) |
|
|
|
-0.7
(-1.4, 0) |
Comparison to
Finasteride alone (95% CI) |
|
|
|
-1.8
(-2.5, -1.1) |