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P0008 Efficacy of pramipexole by clinician and patient assessment during a polysomnographic (PSG) study of restless legs syndrome (RLS)
Posters / Sleep Medicine 8 Suppl. 1 (2007) S69–S114 0.125 mg/day (n = 21); from 41.3 to 6.5 for 0.25 mg/day (n = 22); from 42.5 to 8.9 for 0.50 mg/day (n = 22); and from 40.1 to 9.2 for 0.75 mg/day (n = 21). Thus, mean reductions were −41.1, −34.8, −33.6, and −30.9, respectively. The adjusted mean difference from placebo (on the log scale) was −1.7 (P < 0.0001). By pramipexole dosage, the adjusted mean difference from placebo was −1.5 for 0.125 mg/day, −1.9 for 0.25 mg/day, −1.9 for 0.50 mg/day, and −1.5 for 0.75 mg/day (P < 0.0001 for each comparison). Conclusion: Pramipexole reduced PLMI, with a mean 80% drop for all dose groups combined. Even with the lowest dose tested (0.125 mg/day), this reduction was highly significant. Contributed support: Study supported by Boehringer Ingelheim International GmbH. Declaration of conflict of interest: MP has received a grant from the Rinnekoti Research Foundation and honoraria totaling less than USD10,000 per year for work on restless legs syndrome. IT and JK are employees of Boehringer Ingelheim. P0008 Efficacy of pramipexole by clinician and patient assessment during a polysomnographic (PSG) study of restless legs syndrome (RLS) K. Hirvonen1,2 *, M. Partinen1 , L. Jama1 , A. Alakuijala1 , C. Hublin3,4 , I. Tamminen5 , J. Koester6 . 1 Rinnekoti Research Centre, Espoo, Finland, 2 Neurotest Tampere Oy, Tampere, Finland, 3 Finnish Institute of Occupational Health, Brain@Work Research Center, Helsinki, Finland, 4 Department of Neurology, University of Helsinki, Helsinki, Finland, 5 Medical Division, Boehringer Ingelheim Finland Ky, Helsinki, Finland, 6 Medical Division, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Purpose: The dopamine agonist pramipexole has been found beneficial in RLS. Here polysomnography was accompanied by evaluations to show whether objective PSG change is paralleled by subjective improvement. Methods: The study, a 3-week, randomized, placebo-controlled trial of pramipexole at 0.125, 0.25, 0.50, or 0.75 mg/day, enrolled 109 patients with RLS. At baseline, each patient met all criteria of the International RLS Study Group and scored >15 on the Group’s Rating Scale (IRLS). At endpoint, patients assessed themselves by IRLS and also by the Patient Global Impression scale (PGI), describing their health as “no change”; “a little,” “much,” or “very much” better; or “a little,” “much,” or “very much” worse. For their part, clinicians evaluated patients by the Clinical Global Impressions-Improvement scale (CGI-I), describing their condition as “no change”; “minimally,” “much,” or “very much” improved; or “minimally,” “much,” or “very much” worse. PSG findings measured the periodic limb movements during sleep index (PLMSI). PLMSI data were analyzed by rank sum test, IRLS by analysis of covariance with covariate baseline score, and PGI and CGI-I by Fisher exact test. Results: At endpoint, PLMSI showed a decrease for all pramipexole dosages, by medians of −17.0 to −26.7 vs −3.5 for placebo (P < 0.01 or P < 0.001 for each dose group vs placebo). On IRLS, the adjusted mean change was −15.1 for pramipexole vs −6.1 for placebo (P < 0.0001). On PGI, the proportion of patients judging themselves to be either “much” or “very much” better was 59.3% vs 38.1% (P = 0.0812). On CGI-I, the proportion of patients considered “much” or “very much” improved was 75.6% vs 42.9% (P = 0.0038). Conclusion: During pramipexole therapy for RLS, objective improvement was accompanied by significant subjective benefits, as judged by clinicians and by patients themselves, and on an RLS-specific scale (IRLS) as well as generic scales (PGI and CGI-I). Contributed support: Study supported by Boehringer Ingelheim International GmbH. Declaration of conflict of interest: MP has received a grant from the Rinnekoti Research Foundation and honoraria totaling less than USD10,000 per year for work on restless legs syndrome. IT and JK are employees of Boehringer Ingelheim.
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P0009 Sleep self-assessment by visual analogue scales (VASs) in a 6-week European trial of pramipexole for restless legs syndrome (RLS) K. Stiasny-Kolster1 *, W.H. Oertel1 , B. Bergtholdt2 , Y. Hallstr¨om3 , J. Albo4 , L. Leissner5 , T. Schindler6 , for the Pramipexole in Restless Legs Syndrome Study Group. 1 Philipps-University Marburg, Marburg, Germany, 2 Emovis GmbH, Berlin, Germany, 3 Neuro Center, Stockholm, Sweden, 4 L¨akarhuset V¨allingby, V¨allingby, Sweden, 5 Neurologiska Kliniken, Orebro, ¨ Sweden, 6 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany Purpose: Sleep disruption is a crucial facet of RLS. Here VASs enabled patients to evaluate the sleep-related benefit of the dopamine agonist pramipexole. Methods: Among 345 patients with RLS enrolled in a 6-week, doubleblind, randomized, placebo-controlled pramipexole trial, the 230 patients allocated to receive active drug were started at 0.125 mg/day. During weeks 2 through 4, the dosage could be increased, in weekly steps, to 0.25, 0.50, or a maximum of 0.75 mg/day, depending on each recipient’s Patient Global Impression scale self-rating. During weeks 5 and 6, dosage was kept at the optimized level. On 100-mm VASs, patients characterized the RLS severity they experienced while getting to sleep, in the course of the night, and in the course of the day, and also their satisfaction with sleep (using decreased scores to mark increased satisfaction). Changes from baseline were analyzed by analysis of covariance adjusted for age and baseline score. Results: The adjusted mean change from baseline RLS severity while getting to sleep was −30.6 mm for pramipexole vs −13.8 mm for placebo (P < 0.0001), representing improvement from baseline means of 56.8 and 52.6, respectively. Adjusted mean change in RLS severity in the course of the night was −32.3 vs −12.4 mm (P < 0.0001), from baseline means of 57.2 and 60.7. Adjusted mean change in RLS severity in the course of the day was −12.1 vs −1.5 mm (P < 0.0001), from baseline means of 32.1 and 32.5. Adjusted mean change in sleep satisfaction was −29.9 vs −13.8 mm (P < 0.0001), from baseline means of 63.0 and 60.4. Conclusions: During pramipexole therapy for RLS, patient self-ratings of sleep quality and of symptoms at bedtime and during the night improved significantly more in the pramipexole group than in the placebo group. In addition to the aforementioned nighttime benefits, pramipexole also demonstrated significant improvements during the daytime. Declaration of conflict of interest: WO holds a patent for pramipexole in RLS and been a consultant to BI and Pfizer. KS-K received a grant from Pfizer and honoraria from BI, GSK, Hoffmann-LaRoche, and Schwartz. TS is an employee of BI. P0010 Sleep self-assessment by visual analogue scales (VASs) in a 12-week US trial of pramipexole for restless legs syndrome (RLS) P.C. Zee1 *, J.W. Winkelman2 , K.D. Sethi3 , C.A. Kushida4 , P.M. Becker5 , J. Koester6 . 1 Departments of Neurology and Neurobiology and Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 2 Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, 3 Department of Neurology, Medical College of Georgia, Augusta, GA, USA, 4 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA, 5 Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA, 6 Medical Division, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Purpose: Dopamine agonists are widely recommended for the treatment of RLS. Because patients with RLS experience sleep disruption, with detriments that extend into the day, large-scale trials must examine the treatment’s relief of both night and day symptoms. Methods: For a randomized, double-blind, controlled trial of pramipexole, 344 adult patients with RLS received placebo (n = 86) or pramipexole (n = 258). During a 3-week run-in phase, the pramipexole recipients were up-titrated to a fixed dose of 0.25, 0.50, or 0.75 mg/day. After the 12-week treatment period, patients used 100-mm VASs to characterize RLS severity while getting to sleep, in the course of the night, and in the course of the day, and also their satisfaction with sleep (using decreased scores to
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P0009 Sleep self-assessment by visual analogue scales (VASs) in a 6-week European trial of pramipexole for restless legs syndrome (RLS) K. Stiasny-Kolster1 *, W.H. Oertel1 , B. Bergtholdt2 , Y. Hallstr¨om3 , J. Albo4 , L. Leissner5 , T. Schindler6 , for the Pramipexole in Restless Legs Syndrome Study Group. 1 Philipps-University Marburg, Marburg, Germany, 2 Emovis GmbH, Berlin, Germany, 3 Neuro Center, Stockholm, Sweden, 4 L¨akarhuset V¨allingby, V¨allingby, Sweden, 5 Neurologiska Kliniken, Orebro, ¨ Sweden, 6 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany Purpose: Sleep disruption is a crucial facet of RLS. Here VASs enabled patients to evaluate the sleep-related benefit of the dopamine agonist pramipexole. Methods: Among 345 patients with RLS enrolled in a 6-week, doubleblind, randomized, placebo-controlled pramipexole trial, the 230 patients allocated to receive active drug were started at 0.125 mg/day. During weeks 2 through 4, the dosage could be increased, in weekly steps, to 0.25, 0.50, or a maximum of 0.75 mg/day, depending on each recipient’s Patient Global Impression scale self-rating. During weeks 5 and 6, dosage was kept at the optimized level. On 100-mm VASs, patients characterized the RLS severity they experienced while getting to sleep, in the course of the night, and in the course of the day, and also their satisfaction with sleep (using decreased scores to mark increased satisfaction). Changes from baseline were analyzed by analysis of covariance adjusted for age and baseline score. Results: The adjusted mean change from baseline RLS severity while getting to sleep was −30.6 mm for pramipexole vs −13.8 mm for placebo (P < 0.0001), representing improvement from baseline means of 56.8 and 52.6, respectively. Adjusted mean change in RLS severity in the course of the night was −32.3 vs −12.4 mm (P < 0.0001), from baseline means of 57.2 and 60.7. Adjusted mean change in RLS severity in the course of the day was −12.1 vs −1.5 mm (P < 0.0001), from baseline means of 32.1 and 32.5. Adjusted mean change in sleep satisfaction was −29.9 vs −13.8 mm (P < 0.0001), from baseline means of 63.0 and 60.4. Conclusions: During pramipexole therapy for RLS, patient self-ratings of sleep quality and of symptoms at bedtime and during the night improved significantly more in the pramipexole group than in the placebo group. In addition to the aforementioned nighttime benefits, pramipexole also demonstrated significant improvements during the daytime. Declaration of conflict of interest: WO holds a patent for pramipexole in RLS and been a consultant to BI and Pfizer. KS-K received a grant from Pfizer and honoraria from BI, GSK, Hoffmann-LaRoche, and Schwartz. TS is an employee of BI. P0010 Sleep self-assessment by visual analogue scales (VASs) in a 12-week US trial of pramipexole for restless legs syndrome (RLS) P.C. Zee1 *, J.W. Winkelman2 , K.D. Sethi3 , C.A. Kushida4 , P.M. Becker5 , J. Koester6 . 1 Departments of Neurology and Neurobiology and Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 2 Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, 3 Department of Neurology, Medical College of Georgia, Augusta, GA, USA, 4 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA, 5 Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA, 6 Medical Division, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Purpose: Dopamine agonists are widely recommended for the treatment of RLS. Because patients with RLS experience sleep disruption, with detriments that extend into the day, large-scale trials must examine the treatment’s relief of both night and day symptoms. Methods: For a randomized, double-blind, controlled trial of pramipexole, 344 adult patients with RLS received placebo (n = 86) or pramipexole (n = 258). During a 3-week run-in phase, the pramipexole recipients were up-titrated to a fixed dose of 0.25, 0.50, or 0.75 mg/day. After the 12-week treatment period, patients used 100-mm VASs to characterize RLS severity while getting to sleep, in the course of the night, and in the course of the day, and also their satisfaction with sleep (using decreased scores to