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1.290 Effect of patient age on pramipexole efficacy in the treatment of restless legs syndrome
Poster Presentations: Related Disorders 1.287 Effectiveness of pramipexole in the treatment of RLS: A 12-weeks non-interventional trial in patients with primary restless legs syndrome (RLS)
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Conclusion: Across 784 RLS patients receiving double-blind treatment for three to 12 weeks, pramipexole was significantly superior to placebo as rated by IRLS. Supported by Boehringer Ingelheim International GmbH.
C. M¨oller1° , I. Eisensehr, J. K¨oster, R. Kohnen Germany
1 Ingelheim,
Objective: To evaluate the effectiveness of pramipexole treatment in patients with primary Restless Legs Syndrome (RLS) in routine practice and, secondarily, the time needed to reach maintenance dose of pramipexole. Method: This was an open-label, 12 week-prospective, non-controlled, non-interventional trial in patients with moderate to severe primary RLS being treated with the non-ergot dopamine agonist pramipexole by neurologists across Germany under routine conditions. RLS severity was measured by the International RLS Study Group Rating Scale (IRLS), the RLS-6 and CGI-I questionnaire. Results: A total of 991 patients (mean age: 63 years, 70% females, 63% pre-treated for RLS) suffering from moderate to severe RLS were evaluated at 325 sites. Median duration of observation was 91 days. Patients were starting with a median initial pramipexole dose of 0.088 mg/d (base), were flexibly titrated and had a median final maintenance dose of 0.35 mg/d. The maintenance dose was reached after four weeks by 65.9% of the patients. RLS severity was clearly improved: IRLS (range 0−40) median total score alleviated from “severe” (27) at baseline to “mild” (8) after 3 months of therapy. Similarly, severity of RLS symptoms as measured with the RLS 6 (range: 0−10) on average improved from severe to very mild symptoms “at bedtime” (median baseline: 7, final visit: 1), “during the night” (7/1), and “during the day when at rest” (4/1). In addition, patients rated sleep quality better (7/2) and daytime tiredness less pronounced (4/1). CGI-I was rated as “much improved” or better in 89% of the patients. Pramipexole treatment was well tolerated: only 23 patients (2.2%) suffered from adverse events, most of which were gastrointestinal and general disorders. Conclusion: Pramipexole showed to be highly effective in the treatment of RLS in routine care. Both, night-time and daytime symptoms were clearly improved after 3 months of treatment. 1.288 Patient-rated efficacy of pramipexole for restless legs syndrome: Results from three double-blind trials S. Albrecht1° , J. Koester Germany
1.289 Dose adjustment during long-term pramipexole treatment for restless legs syndrome B. H¨ogl1° , E. Lainey, S. Albrecht, J. K¨oster Austria
1 Innsbruck,
Objective: Pramipexole is efficacious in restless legs syndrome (RLS), a lifelong disease. Loss of long-term efficacy would prompt increased dosage, so flexible-dosing phases of 3 trials were analyzed for dosage changes after optimization. Method: Patients met International RLS Study Group criteria, with a baseline score >15 on the Group’s RLS severity scale (IRLS). Trials had double-blind (DB), placebo-controlled phases and open-label (OL), flexible-dosing phases. A 3-week DB trial (Trial A) was followed by 1-week washout and a 26-week OL phase. A 6-week DB trial (Trial-B) was followed by a 46-week phase: DB for treatment responders; OL for nonresponders. A 12-week DB trial (Trial C) was preceded by a 26-week OL run-in phase. For all patients, pramipexole was initiated at 0.125 mg/d and titrated to achieve satisfactory response (0.75 mg/d maximum). The treatment dosage after 4 weeks was compared with that during the final 3 weeks. Results: Data were available for 97, 260, and 207 patients from Trials A, B, and C, respectively. Overall, 74.1% (418 of 564 patients) maintained a steady dosage throughout flexible-dosing phases, 22.3% (126) increased and 3.5% (20) decreased dosage. In all trials, proportion of patients increasing dosage was greatest at the lowest initial optimized level, but even in that group, 60.3% (38 of 63) required no increase. At initially optimized doses of 0.25 mg/d and 0.50 mg/d, 70.1% (129 of 184) and 68.5% (122 of 178) remained at initial levels, respectively. Conclusion: In 3 studies permitting flexible dosing for 26 or 46 weeks, three-fourths of patients receiving pramipexole for RLS remained at a dosage established by 4 weeks’ titration, indicating a sustained efficacy of pramipexole up to 1 year. Disclosure: Supported by Boehringer Ingelheim International GmbH.
1 Ingelheim,
Objective: To evaluate, in large numbers of patients, the responsiveness of RLS to pramipexole therapy, utilizing the 10-question International RLS scale (IRLS). Method: Data were analyzed from three randomized, placebo-controlled, double-blind trials of pramipexole taken once-daily. Fixed doses of 0.125, 0.25, 0.50, or 0.75 mg/day were studied in a 3-week trial at one Finnish center; optimized doses of 0.125, 0.25, 0.50, or 0.75 mg/day in a 6-week trial at 37 Austrian, German, Norwegian, Dutch, and Swedish centers; and fixed doses of 0.25, 0.50, or 0.75 mg/day in a 12-week trial at 43 US centers. All patients met all RLS diagnostic criteria of the International RLS Study Group, and were required to have a baseline IRLS score >15. After each trial’s treatment period, IRLS scores were re-obtained. Analysis of covariance (ANCOVA) and Cochran-Mantel-Haenszel test were used for statistical analyses. Results: Across all trials, IRLS data were available for 564 patients randomized to receive pramipexole and 220 patients randomized to placebo. At baseline, the mean IRLS score ranged from 22.7 to 24.7 for the pramipexole group in each trial, and from 22.9 to 24.9 for each placebo group. The pooled population represented moderate to severe RLS. At endpoint, the mean IRLS change, adjusted for baseline and patient age, ranged from −12.3 to −15.1 for pramipexole, compared with −5.7 to −9.3 for placebo (p 0.0001 in each trial, as analyzed by ANCOVA). Overall, 59.4% of pramipexole recipients achieved at least a 50% decrease from their baseline score, compared with 34.5% among placebo recipients (p < 0.0001 by Cochran–Mantel–Haenszel test).
1.290 Effect of patient age on pramipexole efficacy in the treatment of restless legs syndrome T. Zesiewicz1° , E. Lainey, J. K¨oster, S. Albrecht FL, USA
1 Tampa,
Objective: Restless legs syndrome (RLS) is characterized by an irresistible urge to move the legs. Pramipexole has been found effective as RLS treatment. In data from three clinical trials, we assessed its age-related benefit. Method: The three double-blind, placebo-controlled trials of 3−12 weeks studied fixed or optimized pramipexole doses of 0.125 to 0.75 mg/d. Patients, 18−80 years old, met International RLS Study Group diagnostic criteria, with a baseline score >15 on the Group’s RLS severity scale (IRLS). At endpoint, IRLS scores were remeasured. Score change in age groups <65 and 65 years was assessed by ANCOVA. Results: In the younger group, 450 patients (72.1% of 624) received pramipexole. Across the three trials, mean change in IRLS score (adjusted for baseline and age) ranged from −12.8 to −15.5. Among 174 placebo recipients, the range was −5.8 to −9.8. In the older group, 114 patients (71.3% of 160) received pramipexole. Adjusted mean change in IRLS score was −10.3 to −15.2, compared with −5.5 to −10.2 among 46 placebo recipients. From trial to trial, adjusted mean difference between pramipexole and placebo ranged from −3.7 to −9.6 in younger patients (P.0029) and from −4.9 to −6.2 in older patients (P = 0.0572 to 0.2015). Overall, adjusted treatment effect was −5.9 (P < 0.0001) in younger and
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−5.2 (P = 0.0033) in older patients. Type and frequency of adverse events were similar in both age groups. Conclusion: By IRLS score, the benefit of pramipexole against RLS in patients 65 years old was similar to that in patients <65 and was significantly different from placebo in the larger, younger groups. Adverse event profiles between groups were similar. Disclosure: Supported by Boehringer Ingelheim International GmbH.
1.291 Improvement in activities of daily living among patients receiving pramipexole for restless legs syndrome (RLS) E. Lainey1° , J. Koester USA
1 Ridgefield,
Objective: To assess the impact of pramipexole therapy on daily affairs and QOL in patients with RLS. Method: Randomized, DB 3-, 6-, and 12-week trials of pramipexole taken once daily. Patients met all RLS diagnostic criteria of the International RLS Study Group (baseline score >15 on the IRLS scale). A total of 564 pramipexole and 220 placebo recipients contributed analyzable data. All trials utilized Question 9 of the IRLS (impact of RLS on daily affairs [0 = none to 4 = very severe]). Additionally, 3- and 6-week trials administered the SF-36 test, which includes social functioning; the 12-week trial administered the Johns Hopkins RLS-QOL, measuring daily activities, physical functioning, and vitality. Results: On IRL Question 9, pramipexole recipients improved by a mean of 0.9 (baseline: 1.4), vs placebo, 0.6 (baseline: 1.5). Pramipexole produced significantly greater Wilcoxon–Mann-Whitney change than placebo for the 6- (P = 0.0319) and 12- (P = 0.0294) week trials and overall (P = 0.0009). Of 378 patients with baseline scores 2, 77% pramipexole improved to 1, vs 56% placebo (P0.0001, Cochran–Mantel–Haenszel test). In 3- and 6week trials, SF-36 social functioning improved with pramipexole (adjusted mean 4.8) (n = 82) and 6.0 (n = 222), while placebo worsened by −5.4 (n = 20; P = 0.0026 ANCOVA) and −0.3 (n = 114; P = 0.0027 ANCOVA), respectively. In the 12-week trial, the adjusted mean RLS-QOL score for pramipexole (n = 249) improved 19.9 points (baseline: 69.2), vs placebo, 13.5 points (baseline: 69.1) (n = 82; P < 0.0001 ANCOVA). Conclusion: Daily life of DB pramipexole RLS patients significantly improved by IRLS Question 9, SF-36 social functioning, and RLS-QOL vs placebo. Supported by Boehringer Ingelheim International GmbH.
1.292 Beneficial impact of pramipexole on social functioning in patients with restless legs syndrome T. Zesiewicz1° , J. K¨oster, S. Albrecht, E. Lainey FL, USA
1 Tampa,
Objective: Restless legs syndrome (RLS) can have a profound effect on quality of life (QOL). The nonergot dopamine agonist pramipexole is effective therapy for RLS. In 3 clinical trials, patients evaluated the treatment’s impact on their QOL, including social functioning. Method: Data from 3 double-blind, placebo-controlled trials of pramipexole at doses of 0.125 to 0.75 mg/d were analyzed. Patients met all RLS diagnostic criteria of the International RLS Study Group, with a baseline score >15 on the Group’s RLS severity scale (IRLS). Threeand 6-week trials utilized the SF-36, a generic questionnaire assessing 8 QOL dimensions, including social functioning. The 12-week trial utilized the Johns Hopkins RLS-QOL, an RLS-specific questionnaire assessing 5 dimensions, including social life. Results: In the 3- and 6-week trials, SF-36 data were available for 82 of the 86 and 222 of the 224 pramipexole recipients, respectively, and for 20 of 21 and 114 of 114 placebo recipients. In both trials, most dimensions exhibited minimal changes, but by ANCOVA (adjusting for age and baseline), social functioning showed a significant treatment effect. In the 3-week trial, adjusted mean improvement was +4.8 (±1.4)
among pramipexole recipients, compared with a −5.4 (±2.9) worsening for placebo (P = 0.0026). In the 6-week trial, improvement was +6.0 (±1.2) vs −0.3 (±1.7; P = 0.0027). In the 12-week trial, RLS-QOL data were available for 253 of the 254 pramipexole recipients and 83 of the 85 placebo recipients. Adjusted mean improvement was 19.9 (±0.8) for pramipexole vs 13.5 (±1.4) for placebo (P < 0.0001). Conclusion: In 3 double-blind multinational trials, pramipexole produced a substantial improvement in QOL of patients with RLS, notably in their social functioning, as assessed by a generic rating (SF-36) and an RLSspecific one (RLS-QOL). Supported by Boehringer Ingelheim International GmbH.
1.293 Ropinirole CR improves the symptoms of restless legs syndrome from the first night of treatment R. Bogan1° , M. Castiglia USA
1 Columbia,
Objective: Restless Legs Syndrome (RLS) symptoms can have a negative impact on sleep and quality of life, therefore rapid treatment with sustained efficacy is desirable. Onset of effect of a once-daily, 14-hour extended-release treatment formulation – ropinirole CR – was assessed in patients with moderate-to-severe primary RLS. Method: In a 12-week pivotal study (protocol 101468/205), patients with moderate-to-severe primary RLS were randomized to ropinirole CR (n = 189), 0.5−6 mg/day, or placebo (n = 195), titrated as needed and tolerated, taken once daily (4pm), 1−2 hours before usual RLS symptom onset. Onset of effect was assessed by proportion of responders (rated ‘very much’ or ‘much’ improved) on the Patient Global Improvement (PGI) scale at Days 2−4 and the Clinical Global Impression–Improvement (CGI-I) scale at Week 1 observed case (OC) through to Week 12 last observation carried forward (LOCF; secondary endpoint), and by mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 1 OC through to Week 12 LOCF (primary endpoint). Results: The proportion of PGI scale responders was significantly greater for ropinirole CR versus placebo on Days 2 (30% versus 12%, after the first night of treatment), 3 (35% versus 18%), and 4 (42% versus 24%); all p < 0.001. The proportion of CGI-I scale responders was also significantly greater for ropinirole CR versus placebo at Week 1 OC (adjusted odds ratio [AOR]: 2.6; p < 0.001) through to Week 12 LOCF (AOR: 4.6; p < 0.001). Mean change from baseline in IRLS total score beginning at Week 1 OC through to Week 12 LOCF was significantly greater (improved) for ropinirole CR versus placebo (adjusted mean treatment difference: Week 1 OC, −3.8; Week 12 LOCF, −5.9; both p < 0.001). Conclusion: Ropinirole CR significantly improves RLS symptoms from the first night of treatment compared with placebo and this treatment benefit is sustained through 12 weeks.
1.294 Tolerability with no loss of efficacy after overnight conversion from immediate-release ropinirole to an extended-release formulation – ropinirole CR – in restless legs syndrome S. Isaacson1° , M. Castiglia, R. Hodge Raton, FL, USA
1 Boca
Objective: Many patients with primary Restless Legs Syndrome (RLS) experience symptoms in the late afternoon/early evening and during the night, and may benefit from extended-duration treatment. The tolerability and safety of overnight conversion from ropinirole immediate release (IR) to a 14-hour extended-release formulation, ropinirole CR, was evaluated in patients with moderate-to-severe primary RLS. Method: In a 4-week, randomized, double-blind, double-dummy, threecohort study (protocol 101468/805), patients taking ropinirole IR for RLS entered cohort A, B, or C based on their stable dose of ropinirole IR (1 mg, 2 mg, or 4 mg, respectively). They were then randomized to one of two
S73
Conclusion: Across 784 RLS patients receiving double-blind treatment for three to 12 weeks, pramipexole was significantly superior to placebo as rated by IRLS. Supported by Boehringer Ingelheim International GmbH.
C. M¨oller1° , I. Eisensehr, J. K¨oster, R. Kohnen Germany
1 Ingelheim,
Objective: To evaluate the effectiveness of pramipexole treatment in patients with primary Restless Legs Syndrome (RLS) in routine practice and, secondarily, the time needed to reach maintenance dose of pramipexole. Method: This was an open-label, 12 week-prospective, non-controlled, non-interventional trial in patients with moderate to severe primary RLS being treated with the non-ergot dopamine agonist pramipexole by neurologists across Germany under routine conditions. RLS severity was measured by the International RLS Study Group Rating Scale (IRLS), the RLS-6 and CGI-I questionnaire. Results: A total of 991 patients (mean age: 63 years, 70% females, 63% pre-treated for RLS) suffering from moderate to severe RLS were evaluated at 325 sites. Median duration of observation was 91 days. Patients were starting with a median initial pramipexole dose of 0.088 mg/d (base), were flexibly titrated and had a median final maintenance dose of 0.35 mg/d. The maintenance dose was reached after four weeks by 65.9% of the patients. RLS severity was clearly improved: IRLS (range 0−40) median total score alleviated from “severe” (27) at baseline to “mild” (8) after 3 months of therapy. Similarly, severity of RLS symptoms as measured with the RLS 6 (range: 0−10) on average improved from severe to very mild symptoms “at bedtime” (median baseline: 7, final visit: 1), “during the night” (7/1), and “during the day when at rest” (4/1). In addition, patients rated sleep quality better (7/2) and daytime tiredness less pronounced (4/1). CGI-I was rated as “much improved” or better in 89% of the patients. Pramipexole treatment was well tolerated: only 23 patients (2.2%) suffered from adverse events, most of which were gastrointestinal and general disorders. Conclusion: Pramipexole showed to be highly effective in the treatment of RLS in routine care. Both, night-time and daytime symptoms were clearly improved after 3 months of treatment. 1.288 Patient-rated efficacy of pramipexole for restless legs syndrome: Results from three double-blind trials S. Albrecht1° , J. Koester Germany
1.289 Dose adjustment during long-term pramipexole treatment for restless legs syndrome B. H¨ogl1° , E. Lainey, S. Albrecht, J. K¨oster Austria
1 Innsbruck,
Objective: Pramipexole is efficacious in restless legs syndrome (RLS), a lifelong disease. Loss of long-term efficacy would prompt increased dosage, so flexible-dosing phases of 3 trials were analyzed for dosage changes after optimization. Method: Patients met International RLS Study Group criteria, with a baseline score >15 on the Group’s RLS severity scale (IRLS). Trials had double-blind (DB), placebo-controlled phases and open-label (OL), flexible-dosing phases. A 3-week DB trial (Trial A) was followed by 1-week washout and a 26-week OL phase. A 6-week DB trial (Trial-B) was followed by a 46-week phase: DB for treatment responders; OL for nonresponders. A 12-week DB trial (Trial C) was preceded by a 26-week OL run-in phase. For all patients, pramipexole was initiated at 0.125 mg/d and titrated to achieve satisfactory response (0.75 mg/d maximum). The treatment dosage after 4 weeks was compared with that during the final 3 weeks. Results: Data were available for 97, 260, and 207 patients from Trials A, B, and C, respectively. Overall, 74.1% (418 of 564 patients) maintained a steady dosage throughout flexible-dosing phases, 22.3% (126) increased and 3.5% (20) decreased dosage. In all trials, proportion of patients increasing dosage was greatest at the lowest initial optimized level, but even in that group, 60.3% (38 of 63) required no increase. At initially optimized doses of 0.25 mg/d and 0.50 mg/d, 70.1% (129 of 184) and 68.5% (122 of 178) remained at initial levels, respectively. Conclusion: In 3 studies permitting flexible dosing for 26 or 46 weeks, three-fourths of patients receiving pramipexole for RLS remained at a dosage established by 4 weeks’ titration, indicating a sustained efficacy of pramipexole up to 1 year. Disclosure: Supported by Boehringer Ingelheim International GmbH.
1 Ingelheim,
Objective: To evaluate, in large numbers of patients, the responsiveness of RLS to pramipexole therapy, utilizing the 10-question International RLS scale (IRLS). Method: Data were analyzed from three randomized, placebo-controlled, double-blind trials of pramipexole taken once-daily. Fixed doses of 0.125, 0.25, 0.50, or 0.75 mg/day were studied in a 3-week trial at one Finnish center; optimized doses of 0.125, 0.25, 0.50, or 0.75 mg/day in a 6-week trial at 37 Austrian, German, Norwegian, Dutch, and Swedish centers; and fixed doses of 0.25, 0.50, or 0.75 mg/day in a 12-week trial at 43 US centers. All patients met all RLS diagnostic criteria of the International RLS Study Group, and were required to have a baseline IRLS score >15. After each trial’s treatment period, IRLS scores were re-obtained. Analysis of covariance (ANCOVA) and Cochran-Mantel-Haenszel test were used for statistical analyses. Results: Across all trials, IRLS data were available for 564 patients randomized to receive pramipexole and 220 patients randomized to placebo. At baseline, the mean IRLS score ranged from 22.7 to 24.7 for the pramipexole group in each trial, and from 22.9 to 24.9 for each placebo group. The pooled population represented moderate to severe RLS. At endpoint, the mean IRLS change, adjusted for baseline and patient age, ranged from −12.3 to −15.1 for pramipexole, compared with −5.7 to −9.3 for placebo (p 0.0001 in each trial, as analyzed by ANCOVA). Overall, 59.4% of pramipexole recipients achieved at least a 50% decrease from their baseline score, compared with 34.5% among placebo recipients (p < 0.0001 by Cochran–Mantel–Haenszel test).
1.290 Effect of patient age on pramipexole efficacy in the treatment of restless legs syndrome T. Zesiewicz1° , E. Lainey, J. K¨oster, S. Albrecht FL, USA
1 Tampa,
Objective: Restless legs syndrome (RLS) is characterized by an irresistible urge to move the legs. Pramipexole has been found effective as RLS treatment. In data from three clinical trials, we assessed its age-related benefit. Method: The three double-blind, placebo-controlled trials of 3−12 weeks studied fixed or optimized pramipexole doses of 0.125 to 0.75 mg/d. Patients, 18−80 years old, met International RLS Study Group diagnostic criteria, with a baseline score >15 on the Group’s RLS severity scale (IRLS). At endpoint, IRLS scores were remeasured. Score change in age groups <65 and 65 years was assessed by ANCOVA. Results: In the younger group, 450 patients (72.1% of 624) received pramipexole. Across the three trials, mean change in IRLS score (adjusted for baseline and age) ranged from −12.8 to −15.5. Among 174 placebo recipients, the range was −5.8 to −9.8. In the older group, 114 patients (71.3% of 160) received pramipexole. Adjusted mean change in IRLS score was −10.3 to −15.2, compared with −5.5 to −10.2 among 46 placebo recipients. From trial to trial, adjusted mean difference between pramipexole and placebo ranged from −3.7 to −9.6 in younger patients (P.0029) and from −4.9 to −6.2 in older patients (P = 0.0572 to 0.2015). Overall, adjusted treatment effect was −5.9 (P < 0.0001) in younger and
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−5.2 (P = 0.0033) in older patients. Type and frequency of adverse events were similar in both age groups. Conclusion: By IRLS score, the benefit of pramipexole against RLS in patients 65 years old was similar to that in patients <65 and was significantly different from placebo in the larger, younger groups. Adverse event profiles between groups were similar. Disclosure: Supported by Boehringer Ingelheim International GmbH.
1.291 Improvement in activities of daily living among patients receiving pramipexole for restless legs syndrome (RLS) E. Lainey1° , J. Koester USA
1 Ridgefield,
Objective: To assess the impact of pramipexole therapy on daily affairs and QOL in patients with RLS. Method: Randomized, DB 3-, 6-, and 12-week trials of pramipexole taken once daily. Patients met all RLS diagnostic criteria of the International RLS Study Group (baseline score >15 on the IRLS scale). A total of 564 pramipexole and 220 placebo recipients contributed analyzable data. All trials utilized Question 9 of the IRLS (impact of RLS on daily affairs [0 = none to 4 = very severe]). Additionally, 3- and 6-week trials administered the SF-36 test, which includes social functioning; the 12-week trial administered the Johns Hopkins RLS-QOL, measuring daily activities, physical functioning, and vitality. Results: On IRL Question 9, pramipexole recipients improved by a mean of 0.9 (baseline: 1.4), vs placebo, 0.6 (baseline: 1.5). Pramipexole produced significantly greater Wilcoxon–Mann-Whitney change than placebo for the 6- (P = 0.0319) and 12- (P = 0.0294) week trials and overall (P = 0.0009). Of 378 patients with baseline scores 2, 77% pramipexole improved to 1, vs 56% placebo (P0.0001, Cochran–Mantel–Haenszel test). In 3- and 6week trials, SF-36 social functioning improved with pramipexole (adjusted mean 4.8) (n = 82) and 6.0 (n = 222), while placebo worsened by −5.4 (n = 20; P = 0.0026 ANCOVA) and −0.3 (n = 114; P = 0.0027 ANCOVA), respectively. In the 12-week trial, the adjusted mean RLS-QOL score for pramipexole (n = 249) improved 19.9 points (baseline: 69.2), vs placebo, 13.5 points (baseline: 69.1) (n = 82; P < 0.0001 ANCOVA). Conclusion: Daily life of DB pramipexole RLS patients significantly improved by IRLS Question 9, SF-36 social functioning, and RLS-QOL vs placebo. Supported by Boehringer Ingelheim International GmbH.
1.292 Beneficial impact of pramipexole on social functioning in patients with restless legs syndrome T. Zesiewicz1° , J. K¨oster, S. Albrecht, E. Lainey FL, USA
1 Tampa,
Objective: Restless legs syndrome (RLS) can have a profound effect on quality of life (QOL). The nonergot dopamine agonist pramipexole is effective therapy for RLS. In 3 clinical trials, patients evaluated the treatment’s impact on their QOL, including social functioning. Method: Data from 3 double-blind, placebo-controlled trials of pramipexole at doses of 0.125 to 0.75 mg/d were analyzed. Patients met all RLS diagnostic criteria of the International RLS Study Group, with a baseline score >15 on the Group’s RLS severity scale (IRLS). Threeand 6-week trials utilized the SF-36, a generic questionnaire assessing 8 QOL dimensions, including social functioning. The 12-week trial utilized the Johns Hopkins RLS-QOL, an RLS-specific questionnaire assessing 5 dimensions, including social life. Results: In the 3- and 6-week trials, SF-36 data were available for 82 of the 86 and 222 of the 224 pramipexole recipients, respectively, and for 20 of 21 and 114 of 114 placebo recipients. In both trials, most dimensions exhibited minimal changes, but by ANCOVA (adjusting for age and baseline), social functioning showed a significant treatment effect. In the 3-week trial, adjusted mean improvement was +4.8 (±1.4)
among pramipexole recipients, compared with a −5.4 (±2.9) worsening for placebo (P = 0.0026). In the 6-week trial, improvement was +6.0 (±1.2) vs −0.3 (±1.7; P = 0.0027). In the 12-week trial, RLS-QOL data were available for 253 of the 254 pramipexole recipients and 83 of the 85 placebo recipients. Adjusted mean improvement was 19.9 (±0.8) for pramipexole vs 13.5 (±1.4) for placebo (P < 0.0001). Conclusion: In 3 double-blind multinational trials, pramipexole produced a substantial improvement in QOL of patients with RLS, notably in their social functioning, as assessed by a generic rating (SF-36) and an RLSspecific one (RLS-QOL). Supported by Boehringer Ingelheim International GmbH.
1.293 Ropinirole CR improves the symptoms of restless legs syndrome from the first night of treatment R. Bogan1° , M. Castiglia USA
1 Columbia,
Objective: Restless Legs Syndrome (RLS) symptoms can have a negative impact on sleep and quality of life, therefore rapid treatment with sustained efficacy is desirable. Onset of effect of a once-daily, 14-hour extended-release treatment formulation – ropinirole CR – was assessed in patients with moderate-to-severe primary RLS. Method: In a 12-week pivotal study (protocol 101468/205), patients with moderate-to-severe primary RLS were randomized to ropinirole CR (n = 189), 0.5−6 mg/day, or placebo (n = 195), titrated as needed and tolerated, taken once daily (4pm), 1−2 hours before usual RLS symptom onset. Onset of effect was assessed by proportion of responders (rated ‘very much’ or ‘much’ improved) on the Patient Global Improvement (PGI) scale at Days 2−4 and the Clinical Global Impression–Improvement (CGI-I) scale at Week 1 observed case (OC) through to Week 12 last observation carried forward (LOCF; secondary endpoint), and by mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 1 OC through to Week 12 LOCF (primary endpoint). Results: The proportion of PGI scale responders was significantly greater for ropinirole CR versus placebo on Days 2 (30% versus 12%, after the first night of treatment), 3 (35% versus 18%), and 4 (42% versus 24%); all p < 0.001. The proportion of CGI-I scale responders was also significantly greater for ropinirole CR versus placebo at Week 1 OC (adjusted odds ratio [AOR]: 2.6; p < 0.001) through to Week 12 LOCF (AOR: 4.6; p < 0.001). Mean change from baseline in IRLS total score beginning at Week 1 OC through to Week 12 LOCF was significantly greater (improved) for ropinirole CR versus placebo (adjusted mean treatment difference: Week 1 OC, −3.8; Week 12 LOCF, −5.9; both p < 0.001). Conclusion: Ropinirole CR significantly improves RLS symptoms from the first night of treatment compared with placebo and this treatment benefit is sustained through 12 weeks.
1.294 Tolerability with no loss of efficacy after overnight conversion from immediate-release ropinirole to an extended-release formulation – ropinirole CR – in restless legs syndrome S. Isaacson1° , M. Castiglia, R. Hodge Raton, FL, USA
1 Boca
Objective: Many patients with primary Restless Legs Syndrome (RLS) experience symptoms in the late afternoon/early evening and during the night, and may benefit from extended-duration treatment. The tolerability and safety of overnight conversion from ropinirole immediate release (IR) to a 14-hour extended-release formulation, ropinirole CR, was evaluated in patients with moderate-to-severe primary RLS. Method: In a 4-week, randomized, double-blind, double-dummy, threecohort study (protocol 101468/805), patients taking ropinirole IR for RLS entered cohort A, B, or C based on their stable dose of ropinirole IR (1 mg, 2 mg, or 4 mg, respectively). They were then randomized to one of two