Two controlled clinical studies were conducted with CARDURA XL in BPH patients,
followed by an open-label extension study. Study 1 was a randomized, double-blind,
parallel-group, placebo- and active-controlled study that compared the safety and
efficacy of CARDURA XL (4 or 8 mg/day) with that of doxazosin IR (1, 2, 4, or 8
mg/day) and placebo over 13 weeks in 795 BPH patients, of whom 317 were randomized
to CARDURA XL. Study 2 was a randomized, double-blind, parallel-group, active-controlled
study that compared the safety and efficacy of CARDURA XL (4 or 8 mg/day) with that
of doxazosin IR (1, 2, 4, or 8 mg/day) over 13 weeks in 680 BPH patients, of whom
350 were randomized to CARDURA XL.
In both studies, men aged 50-80 years with symptomatic benign prostatic hyperplasia
(BPH) were enrolled. Symptomatic BPH was defined as a total score of at least 12
points on the 35-point International Prostate Symptom Score (IPSS) and a maximum
urinary flow rate of ≤ 15 mL/sec but no less than 5 mL/sec (total voided volume
≥ 150 mL). In these two studies, conducted in a total of 1475 patients, the mean
age was 64 years (range 47-83 years). Patients were Caucasian (96%), Black (1.5%),
Asian (1.5%), and of Other ethnicity (1%).
In both studies, CARDURA XL dosing was initiated after a 2 week placebo-run in period
at 4 mg per day increasing to 8 mg per day after 7 weeks of treatment if adequate
response (defined as having both an increase in maximum urinary flow rate of at
least 3 mL/sec and a decrease in total IPSS of at least 30% from baseline) was not
seen. Doxazosin IR was titrated from an initial dose of 1 mg daily to 2 mg daily
after 1 week with the option to increase to 4 mg daily after 3 weeks and then to
a maximum of 8 mg daily after 7 weeks if an adequate response was not seen. The
final daily dose of CARDURA XL was 4 mg in 43% of patients and was 8 mg in 57% of
patients. The final daily dose of doxazosin IR was 1 mg in 1%, 2 mg in 12%, 4 mg
in 30% of patients and 8 mg in 57% of patients.
There were two primary efficacy variables in each of these two controlled clinical
studies: the International Prostate Symptom Score (IPSS) and the peak urinary flow
rate (Qmax). The IPSS consists of seven questions that
assess the severity of both irritative (frequency, urgency, nocturia) and obstructive
(incomplete emptying, stopping and starting, weak stream, and pushing or straining)
symptoms, with possible total scores ranging from 0 to 35. The Qmax
was measured in both studies just prior to the next dose. The results for total
symptom score are given in Table 2, and for maximum urinary flow rate in Table 3.
Table 2: Total International Prostate Symptom Score (IPSS)
Table 3: Maximum Flow Rate (mL/sec)
Mean changes in IPSS scores for CARDURA XL and placebo in Study 1 are summarized
in Figure 2.
Figure 2: Mean Change (+SE) in Total IPSS Score by Visit in Study 1
Mean changes in maximum urinary flow rate (Qmax) for both
CARDURA XL and placebo in Study 1 are summarized in Figure 3.
Figure 3: Mean Change (+SE) in Maximum Urinary Flow Rate (mL/sec) by Visit in Study
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