Long-term efficacy and safety of PRO 160/120 (a combination of Sabal and Urtica extract) in patients with lower urinary tract symptoms (LUTS). (Short Communication).
Due to their mechanisms of action (Koch, 2001; Goepel et al. 1999; Duker et al. 1989; Koch and Biber, 1994; Hirano et al. 1994; Lichius et al. 1999), a combination of sabal fruit extract and urtica root extract promises to be effective in the treatment of BPH, as the drugs can be expected to show a synergistic effect (e.g. Koch, 2001). PRO 160/120 *, a fixed combination of 160 mg sabal fruit extract (WS [R] 1473 **) and 120 mg urtica root extract (WS [R] 1031 **) per capsule, has already been demonstrated to be effective and safe in double-blind placebo- or reference-controlled clinical trials with durations of up to 48 weeks (Metzker et al. 1996; Sokeland and Albrecht, 1997; Sokeland, 2000). Recently, two long-term studies with a duration of 96 weeks and 60 weeks, respectively, were conducted and first data were presented focussing on the International Prostate Symptom Score (I-PSS), which is now recognised as the standard for assessing treatment efficacy in BPH (Roehrborn et al. 1998 and 2001). Both trials followed current international guidelines.
Sivkov and colleagues (2001) conducted a prospective, randomized, placebo-controlled, double-blind, long-term multicentre trial in 257 patients with LUTS (BPH stage I-II acc. to Alken (1973), I-PSS [greater than or equal to] 14, Quality of Life (QoL) [greater than or equal to] 4, and maximum urinary flow rate ([Q.sub.max]) <15 ml/s) which consisted of a 2-week placebo-run-in-phase followed by a 24-week double-blind treatment (2 X 1 capsule PRO 160/120 vs. placebo), an open 24-week control period (during which all patients received 2 X 1 capsule PRO 160/120) and an open follow-up period of another 48 weeks (all patients receiving 2 X 1 capsule PRO 160/120). At baseline, the 253 patients evaluated (PRO 160/120: 127; placebo: 126) showed a median I-PSS of 17 points in both treatment groups. After the double-blind treatment a statistically significant group difference in the decrease of the I-PSS could be shown (PRO 160/120: -6 points, placebo:-4 points; p = 0.0055, two-sided U-test stratified by centre). After t he control period the I-PSS in the former placebo patients (now also treated with PRO 160/120) was reduced by another 2 points vs. 1 point in those patients having been treated with PRO 160/120 since the beginning of the double-blind treatment. This difference between the two treatment groups was also statistically significant (p = 0.0270, two-sided stratified U-test). At the end of the control period, both treatment groups showed a reduction of 7 points compared to baseline in the I-PSS (p = 0.8025, two-sided stratified U-test). This indicates that patients formerly treated with placebo improved to the same extent during treatment with PRO 160/120 as did those patients who had been treated with PRO 160/120 already since the beginning of the double-blind treatment phase. Both treatment groups showed comparable results concerning the occurrence of adverse events.
A second prospective, randomized, double-blind, double-dummy, multicentre trial compared the efficacy and tolerability of PRO 160/120 vs. tamsulosin in patients with LUTS (symptomatic BPH) (Bondarenko et al. 2002). In total, 140 patients (aged 50 years, I-PSS [greater than or equal to]13, QoL [greater than or equal to]3, [Q.sub.max] [less than or equal to] 12 ml/s) were randomised and--after a placebo-run-in-phase of 2 weeks--treated with 2 x 1 capsule PRO 160/120 (n = 71) or 1 x 1 capsule tamsulosin (n = 69). During the 60 weeks of treatment, the I-PSS improved by 9 points having started with baseline values of 20 points in each group (medians). At the end of the study, 22 (32.4%) of the patients treated with PRO 160/120 and 19 (27.9%) of the patients treated with tamsulosin showed only mild symptoms (i.e. I-PSS [less than or equal to]7) (n = 136; p = 0.03, test for non-inferiority according to Farrington-Manning; equivalence margin: 10%). Quality of life of the patients improved by 2 points under PRO 160/12 0 and by 1 point under tamsulosin (baseline values: 3 points vs. 4 points; medians). Adverse events occurred slightly more frequently in the tamsulosin group compared to the PRO 160/120 group.
These latest results underline the efficacy and safety which have already been shown for PRO 160/120 in earlier trials (Metzker et al. 1996; Sokeland and Albrecht, 1997; Sokeland, 2000). The combination of sabal and urtica extract shows clear advantages regarding the patients' 'subjective' apperception and evaluation of LUTS as compared to placebo according to the I-PSS. PRO 160/120 could also be shown to be an effective and safe therapy option in patients with LUTS (symptomatic EPH) which is comparable to the [alpha]-blocker tamsulosin. Both clinical trials underline the excellent tolerability of PRO 160/120 even in the long-term use.
* Marketed in Germany under the trade name Prostagutt[R] forte, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany
** WS [R] 1473 and WS [R] 1031 are registered trademarks of Dr. Willmar Schwabe GmbH & Co. KG
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Boris Bondarenko (1)
Carola Walther (2)
Petra Funk (2)
Sandra Schlafke (2)
Udo Engelmann (1)
(1.) Department of Urology, University Hospital of Cologne, Cologne, Germany
(2.) Clinical Research Department, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany
Boris Bondarenko, Klinik und Poliklinik fur Urologie, Universitat Koln, Joseph-Stelzmann-Stra[beta]e 9, D - 50931 Koln, Germany
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