- Email: [email protected]
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
S74
Monday, 10 December 2007
−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
Poster Presentations: Related Disorders dosing groups within each cohort and entered a 4-week treatment phase. At pre-identified clinic visits, patients in each dosing group were converted overnight to ropinirole CR for 1 week (patients in cohorts A, B, and C were converted to 2 mg, 3 mg, and 6 mg of ropinirole CR, respectively). To maintain blinding and allow comparison between groups, at each conversion timepoint, one dosing group underwent actual conversion to ropinirole CR, while the second group underwent a “dummy” conversion. Primary endpoint: incidence of post-conversion-emergent adverse events (AEs); defined as first occurrence/new episode/increase in severity of an AE. Efficacy was assessed using the International Restless Legs Scale (IRLS). Results: In cohorts A, B, and C, post-conversion-emergent AEs (any) were reported by 37% (n = 17), 33% (n = 16), and 46% (n = 13) of patients, respectively, following actual conversion and by 43% (n = 20), 37% (n = 18), and 36% (n = 10) of patients, respectively, following dummy conversion (combined conversion groups). No patients were withdrawn from cohorts A or C due to post-conversion AEs. There was no loss of efficacy following actual conversion to ropinirole CR, based on mean change from pre- to post-conversion in IRLS total score. Conclusion: Overnight conversion from ropinirole IR to ropinirole CR was generally well tolerated without loss of efficacy.
1.295 Ropinirole CR significantly improves quality of life in patients with restless legs syndrome R. Bogan1° , N. Williams USA
1 Columbia,
Objective: Restless Legs Syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs. RLS can have a negative impact on patients’ health-related quality of life (HRQoL), and patients may report a disease burden similar to that of other chronic medical conditions, such as heart disease and clinical depression. Many patients with RLS experience symptoms that occur in the late afternoon/early evening and during the night. A once-daily, extended-release formulation – ropinirole CR – provides up to 14 hours of treatment coverage in patients with RLS. Method: Study 101468/205 was a 12-week, randomized, double-blind, placebo-controlled trial. 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 onset of RLS symptoms. Primary endpoint was mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 12 last observation carried forward (LOCF). HRQoL was assessed using mean change from baseline in Overall Life Impact score of the patient-reported, disease-specific RLS Quality of Life (RLSQoL) questionnaire, and in domain scores of the non-disease-specific Short-Form36 (SF-36) Health Survey at Week 12 LOCF. Results: Baseline demographics and characteristics were similar between treatment groups. At Week 12 LOCF, mean change from baseline in IRLS total score was significantly greater (improved) for ropinirole CR versus placebo (adjusted mean treatment difference [AMTD]: −5.9; p < 0.001). A significantly greater improvement from baseline in mean RLSQoL score was seen for ropinirole CR versus placebo at Week 12 LOCF (AMTD: 9.1; p < 0.001). In addition, a larger improvement was observed for ropinirole CR versus placebo in all domains of the SF-36 at Week 12 LOCF (not tested). Conclusion: Ropinirole CR significantly reduces RLS symptoms and improves overall HRQoL in patients with moderate-to-severe primary RLS.
S75
1.296 Ropinirole CR reduces sleep disturbance in patients with moderate-to-severe primary restless legs syndrome: Results from a 12-week pivotal study R. Bogan1° , N. Williams USA
1 Columbia,
Objective: The symptoms of Restless Legs Syndrome (RLS) are often associated with sleep disturbance. Many patients with RLS experience symptoms that present in the late afternoon/early evening and during the night. The efficacy and safety of a 14-hour once-daily, extended-release formulation – ropinirole CR – were assessed in patients with moderateto-severe primary RLS and the effects of treatment on RLS symptomassociated sleep disturbance are presented here. Method: In a 12-week pivotal study (protocol 101468/205), patients with moderate-to-severe primary RLS were randomized to receive 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 onset of RLS symptoms. Efficacy endpoints included mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 12 last observation carried forward (LOCF; primary endpoint) and four domains assessed by the patient-completed Medical Outcomes Study (MOS) Sleep Scale at Week 12 LOCF (secondary endpoint). Safety was assessed by adverse event (AE) reporting and discontinuations due to AEs. Results: At Week 12 LOCF, mean change from baseline in IRLS total score was significantly greater (improved) for ropinirole CR versus placebo treatment (adjusted mean treatment difference [AMTD]: −5.9; p < 0.001) and significantly greater improvements were seen with ropinirole CR versus placebo for the MOS Sleep Scale domains of sleep disturbance, daytime somnolence, sleep adequacy (AMTD: −13.9; −7.9; 12.0, respectively; all p < 0.001), and sleep quantity (AMTD: 0.3 hours; p < 0.05). The most commonly reported AE in the ropinirole CR group was nausea (28%, versus 7% for placebo). AEs leading to withdrawal during treatment were low and comparable between treatment groups (ropinirole CR, 4%; placebo, 3%). Conclusion: Ropinirole CR improves RLS symptoms, significantly reduces associated sleep disturbance, improves sleep adequacy and quantity, reduces daytime somnolence and is generally well tolerated in patients with moderate-to-severe primary RLS.
1.297 Rotigotine transdermal patch is effective in the treatment of idiopathic RLS: Results of a 6 month, multicenter, double blind, placebo controlled trial in Europe C. Trenkwalder1° , K.R. Chaudhuri, L. Ferini Strambi, D. GarciaBorreguero, B. Hoegl, J. Keffel, R. Kohnen, W. Poewe, E. Schollmayer, K. Stiasny-Kolster, W.H. Oertel 1 Kassel, Germany Objective: The aim of this multicenter trial was to evaluate efficacy and safety of the rotigotine transdermal patch in patients with moderate to very severe idiopathic RLS over a period of 6 months. Method: The study was performed as a multicenter, randomized, doubleblind, placebo-controlled, 4-arm parallel-group trial with 3 fixed doses of rotigotine 1−3 mg/24 h (5−15 cm2 ). The co-primary efficacy parameters were the IRLS sum score and the CGI item I (severity of illness). Secondary parameters included RLS-6 and QoL-RLS and safety data. Results: 458 patients (58±11 years, 73% female) were randomized at 49 sites in 8 European countries. The dropout rate was 41.9% in the placebo and 28.2% in the rotigotine groups. The mean baseline IRLS score was 28.1±6.1 and the mean baseline CGI score was 5.0±0.8. The net effects versus placebo of the improvements after 6 month were −5.1, −7.5, and 8.2 in the IRLS and −0.76, −1.07, and −1.21 in CGI item I for rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h, respectively (p < 0.0001 for all comparisons). Comparable effects were observed in the secondary parameters RLS-6 and QoL-RLS. At least 1 adverse event was reported by 55% of patients on placebo and 78% on rotigotine. Most common side
Monday, 10 December 2007
−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
Poster Presentations: Related Disorders dosing groups within each cohort and entered a 4-week treatment phase. At pre-identified clinic visits, patients in each dosing group were converted overnight to ropinirole CR for 1 week (patients in cohorts A, B, and C were converted to 2 mg, 3 mg, and 6 mg of ropinirole CR, respectively). To maintain blinding and allow comparison between groups, at each conversion timepoint, one dosing group underwent actual conversion to ropinirole CR, while the second group underwent a “dummy” conversion. Primary endpoint: incidence of post-conversion-emergent adverse events (AEs); defined as first occurrence/new episode/increase in severity of an AE. Efficacy was assessed using the International Restless Legs Scale (IRLS). Results: In cohorts A, B, and C, post-conversion-emergent AEs (any) were reported by 37% (n = 17), 33% (n = 16), and 46% (n = 13) of patients, respectively, following actual conversion and by 43% (n = 20), 37% (n = 18), and 36% (n = 10) of patients, respectively, following dummy conversion (combined conversion groups). No patients were withdrawn from cohorts A or C due to post-conversion AEs. There was no loss of efficacy following actual conversion to ropinirole CR, based on mean change from pre- to post-conversion in IRLS total score. Conclusion: Overnight conversion from ropinirole IR to ropinirole CR was generally well tolerated without loss of efficacy.
1.295 Ropinirole CR significantly improves quality of life in patients with restless legs syndrome R. Bogan1° , N. Williams USA
1 Columbia,
Objective: Restless Legs Syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs. RLS can have a negative impact on patients’ health-related quality of life (HRQoL), and patients may report a disease burden similar to that of other chronic medical conditions, such as heart disease and clinical depression. Many patients with RLS experience symptoms that occur in the late afternoon/early evening and during the night. A once-daily, extended-release formulation – ropinirole CR – provides up to 14 hours of treatment coverage in patients with RLS. Method: Study 101468/205 was a 12-week, randomized, double-blind, placebo-controlled trial. 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 onset of RLS symptoms. Primary endpoint was mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 12 last observation carried forward (LOCF). HRQoL was assessed using mean change from baseline in Overall Life Impact score of the patient-reported, disease-specific RLS Quality of Life (RLSQoL) questionnaire, and in domain scores of the non-disease-specific Short-Form36 (SF-36) Health Survey at Week 12 LOCF. Results: Baseline demographics and characteristics were similar between treatment groups. At Week 12 LOCF, mean change from baseline in IRLS total score was significantly greater (improved) for ropinirole CR versus placebo (adjusted mean treatment difference [AMTD]: −5.9; p < 0.001). A significantly greater improvement from baseline in mean RLSQoL score was seen for ropinirole CR versus placebo at Week 12 LOCF (AMTD: 9.1; p < 0.001). In addition, a larger improvement was observed for ropinirole CR versus placebo in all domains of the SF-36 at Week 12 LOCF (not tested). Conclusion: Ropinirole CR significantly reduces RLS symptoms and improves overall HRQoL in patients with moderate-to-severe primary RLS.
S75
1.296 Ropinirole CR reduces sleep disturbance in patients with moderate-to-severe primary restless legs syndrome: Results from a 12-week pivotal study R. Bogan1° , N. Williams USA
1 Columbia,
Objective: The symptoms of Restless Legs Syndrome (RLS) are often associated with sleep disturbance. Many patients with RLS experience symptoms that present in the late afternoon/early evening and during the night. The efficacy and safety of a 14-hour once-daily, extended-release formulation – ropinirole CR – were assessed in patients with moderateto-severe primary RLS and the effects of treatment on RLS symptomassociated sleep disturbance are presented here. Method: In a 12-week pivotal study (protocol 101468/205), patients with moderate-to-severe primary RLS were randomized to receive 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 onset of RLS symptoms. Efficacy endpoints included mean change from baseline in International Restless Legs Scale (IRLS) total score at Week 12 last observation carried forward (LOCF; primary endpoint) and four domains assessed by the patient-completed Medical Outcomes Study (MOS) Sleep Scale at Week 12 LOCF (secondary endpoint). Safety was assessed by adverse event (AE) reporting and discontinuations due to AEs. Results: At Week 12 LOCF, mean change from baseline in IRLS total score was significantly greater (improved) for ropinirole CR versus placebo treatment (adjusted mean treatment difference [AMTD]: −5.9; p < 0.001) and significantly greater improvements were seen with ropinirole CR versus placebo for the MOS Sleep Scale domains of sleep disturbance, daytime somnolence, sleep adequacy (AMTD: −13.9; −7.9; 12.0, respectively; all p < 0.001), and sleep quantity (AMTD: 0.3 hours; p < 0.05). The most commonly reported AE in the ropinirole CR group was nausea (28%, versus 7% for placebo). AEs leading to withdrawal during treatment were low and comparable between treatment groups (ropinirole CR, 4%; placebo, 3%). Conclusion: Ropinirole CR improves RLS symptoms, significantly reduces associated sleep disturbance, improves sleep adequacy and quantity, reduces daytime somnolence and is generally well tolerated in patients with moderate-to-severe primary RLS.
1.297 Rotigotine transdermal patch is effective in the treatment of idiopathic RLS: Results of a 6 month, multicenter, double blind, placebo controlled trial in Europe C. Trenkwalder1° , K.R. Chaudhuri, L. Ferini Strambi, D. GarciaBorreguero, B. Hoegl, J. Keffel, R. Kohnen, W. Poewe, E. Schollmayer, K. Stiasny-Kolster, W.H. Oertel 1 Kassel, Germany Objective: The aim of this multicenter trial was to evaluate efficacy and safety of the rotigotine transdermal patch in patients with moderate to very severe idiopathic RLS over a period of 6 months. Method: The study was performed as a multicenter, randomized, doubleblind, placebo-controlled, 4-arm parallel-group trial with 3 fixed doses of rotigotine 1−3 mg/24 h (5−15 cm2 ). The co-primary efficacy parameters were the IRLS sum score and the CGI item I (severity of illness). Secondary parameters included RLS-6 and QoL-RLS and safety data. Results: 458 patients (58±11 years, 73% female) were randomized at 49 sites in 8 European countries. The dropout rate was 41.9% in the placebo and 28.2% in the rotigotine groups. The mean baseline IRLS score was 28.1±6.1 and the mean baseline CGI score was 5.0±0.8. The net effects versus placebo of the improvements after 6 month were −5.1, −7.5, and 8.2 in the IRLS and −0.76, −1.07, and −1.21 in CGI item I for rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h, respectively (p < 0.0001 for all comparisons). Comparable effects were observed in the secondary parameters RLS-6 and QoL-RLS. At least 1 adverse event was reported by 55% of patients on placebo and 78% on rotigotine. Most common side