14 CLINICAL STUDIES
14.1 Studies in Patients with BPH
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 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%, and 8 mg in 57% of patients.
There were two primary efficacy variables in each of these two controlled clinical studies: the total 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 3, and for maximum urinary flow rate in Table 4.
|MEAN CHANGE (±SE)†|
|Placebo||151||17.9 ± 4.3||-6.1 ± 0.41|
|CARDURA XL||310||17.7 ± 4.3||-8.0 ± 0.30‡|
|Doxazosin IR||311||17.8 ± 4.5||-8.4 ± 0.29‡|
|CARDURA XL||330||18.4 ± 5.0||-8.1 ± 0.30|
|Doxazosin IR||313||18.4 ± 4.8||-7.9 ± 0.31|
|MEAN CHANGE (±SE)*|
|Placebo||151||9.8 ± 2.6||0.8 ± 0.32|
|CARDURA XL||300||10.3 ± 2.6||2.6 ± 0.24†|
|Doxazosin IR||303||10.1 ± 2.7||2.2 ± 0.23†|
|CARDURA XL||322||10.5 ± 2.6||2.7 ± 0.27|
|Doxazosin IR||314||10.6 ± 2.6||2.7 ± 0.27|
Mean changes in IPSS scores for CARDURA XL and placebo in Study 1 are summarized in Figure 2.
Mean changes in maximum urinary flow rate (Qmax) for both CARDURA XL and placebo in Study 1 are summarized in Figure 3.