Pramipexole

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Paolo Barone - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and sustained efficacy of extended release Pramipexole in early and advanced parkinson s disease
    European Journal of Neurology, 2014
    Co-Authors: Robert A Hauser, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, O Rascol, Michael Busse, Mandy Fraessdorf, C Debieuvre, Werner Poewe
    Abstract:

    Background and purpose To assess the long-term safety and efficacy of Pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). Methods In two double-blind (DB) studies of early PD and one of advanced PD, active-treatment arms received Pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375–4.5 mg q.d.). Results Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0% were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to Pramipexole introduction, at −6.6 and −6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of Pramipexole (33 DB plus 80 OL) in early PD, and −11.5 and −9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. Conclusions These results support the long-term safety and efficacy of Pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

  • minimal clinically important difference in parkinson s disease as assessed in pivotal trials of Pramipexole extended release
    Parkinson's Disease, 2014
    Co-Authors: Robert A Hauser, Mark Forrest Gordon, Werner Poewe, Olivier Rascol, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, C Debieuvre, Mandy Frasdorf
    Abstract:

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of Pramipexole ER that included Pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (Pramipexole ER, Pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (Pramipexole ER, Pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  • Pramipexole in patients with early parkinson s disease proud a randomised delayed start trial
    Lancet Neurology, 2013
    Co-Authors: Anthony H V Schapira, Werner Poewe, Paolo Barone, Yoshikuni Mizuno, Michael P Mcdermott, Cynthia L Comella, Stefan Albrecht, Helen H Hsu, Dan Massey, Olivier Rascol
    Abstract:

    Summary Background In models of dopaminergic neuronal loss, the dopamine agonist Pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed Pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Methods Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30–79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or Pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to Pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Findings Of 535 patients, 261 were randomly assigned to receive Pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed Pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early Pramipexole group and 61 patients in the delayed Pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123 I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed Pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early Pramipexole and 179 (84%) patients given delayed Pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early Pramipexole group and 17 (8%) in the delayed Pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. Interpretation By clinical and neuroimaging measures, Pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6–9 months. The results do not support the hypothesis that Pramipexole has disease-modifying effects. Funding Boehringer Ingelheim GmbH.

  • efficacy and safety of extended versus immediate release Pramipexole in japanese patients with advanced and l dopa undertreated parkinson disease a double blind randomized trial
    Clinical Neuropharmacology, 2012
    Co-Authors: Yoshikuni Mizuno, Olivier Rascol, Anthony H V Schapira, Mitsutoshi Yamamoto, Sadako Kuno, Kazuko Hasegawa, Nobutaka Hattori, Tatsuro Kagimura, Akiko Sarashina, Paolo Barone
    Abstract:

    Objectives To compare the efficacy, safety, tolerability, and trough plasma levels of Pramipexole extended-release (ER) and Pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). Methods After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to Pramipexole ER once daily or Pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label Pramipexole ER, beginning with a 4-week dose-adjustment phase. Results Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with Pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to Pramipexole ER. Conclusions In L-dopa-treated patients, Pramipexole ER and Pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from Pramipexole IR to Pramipexole ER with no impact on efficacy.

  • extended release Pramipexole in early parkinson disease a 33 week randomized controlled trial
    Neurology, 2011
    Co-Authors: Werner Poewe, Robert A Hauser, Paolo Barone, Yoshikuni Mizuno, Laurence Salin, Monika Haaksma, Nolwenn Juhel, O Rascol, Anthony H V Schapira
    Abstract:

    Objective: To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist Pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) Pramipexole. Methods: This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to Pramipexole IR, Pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test Pramipexole ER noninferiority to Pramipexole IR based on a change in the Unified Parkinson9s Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed −3 points. Results: Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was −8.2 for ER and −8.7 for IR, a difference of −0.5 with a 95% CI of −2.3 to 1.3. Compared with placebo (n = 103), Pramipexole ER and Pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of Pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. Conclusions: As monotherapy for early PD, Pramipexole ER was noninferior to Pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. Classification of evidence: This study provides Class I evidence that Pramipexole ER is not inferior to Pramipexole IR in patients with early PD. Neurology ® 2011;77:759–766

Werner Poewe - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and sustained efficacy of extended release Pramipexole in early and advanced parkinson s disease
    European Journal of Neurology, 2014
    Co-Authors: Robert A Hauser, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, O Rascol, Michael Busse, Mandy Fraessdorf, C Debieuvre, Werner Poewe
    Abstract:

    Background and purpose To assess the long-term safety and efficacy of Pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). Methods In two double-blind (DB) studies of early PD and one of advanced PD, active-treatment arms received Pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375–4.5 mg q.d.). Results Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0% were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to Pramipexole introduction, at −6.6 and −6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of Pramipexole (33 DB plus 80 OL) in early PD, and −11.5 and −9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. Conclusions These results support the long-term safety and efficacy of Pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

  • minimal clinically important difference in parkinson s disease as assessed in pivotal trials of Pramipexole extended release
    Parkinson's Disease, 2014
    Co-Authors: Robert A Hauser, Mark Forrest Gordon, Werner Poewe, Olivier Rascol, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, C Debieuvre, Mandy Frasdorf
    Abstract:

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of Pramipexole ER that included Pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (Pramipexole ER, Pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (Pramipexole ER, Pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  • Pramipexole in patients with early parkinson s disease proud a randomised delayed start trial
    Lancet Neurology, 2013
    Co-Authors: Anthony H V Schapira, Werner Poewe, Paolo Barone, Yoshikuni Mizuno, Michael P Mcdermott, Cynthia L Comella, Stefan Albrecht, Helen H Hsu, Dan Massey, Olivier Rascol
    Abstract:

    Summary Background In models of dopaminergic neuronal loss, the dopamine agonist Pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed Pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Methods Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30–79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or Pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to Pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Findings Of 535 patients, 261 were randomly assigned to receive Pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed Pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early Pramipexole group and 61 patients in the delayed Pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123 I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed Pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early Pramipexole and 179 (84%) patients given delayed Pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early Pramipexole group and 17 (8%) in the delayed Pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. Interpretation By clinical and neuroimaging measures, Pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6–9 months. The results do not support the hypothesis that Pramipexole has disease-modifying effects. Funding Boehringer Ingelheim GmbH.

  • extended release Pramipexole in early parkinson disease a 33 week randomized controlled trial
    Neurology, 2011
    Co-Authors: Werner Poewe, Robert A Hauser, Paolo Barone, Yoshikuni Mizuno, Laurence Salin, Monika Haaksma, Nolwenn Juhel, O Rascol, Anthony H V Schapira
    Abstract:

    Objective: To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist Pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) Pramipexole. Methods: This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to Pramipexole IR, Pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test Pramipexole ER noninferiority to Pramipexole IR based on a change in the Unified Parkinson9s Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed −3 points. Results: Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was −8.2 for ER and −8.7 for IR, a difference of −0.5 with a 95% CI of −2.3 to 1.3. Compared with placebo (n = 103), Pramipexole ER and Pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of Pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. Conclusions: As monotherapy for early PD, Pramipexole ER was noninferior to Pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. Classification of evidence: This study provides Class I evidence that Pramipexole ER is not inferior to Pramipexole IR in patients with early PD. Neurology ® 2011;77:759–766

  • extended release Pramipexole in advanced parkinson disease a randomized controlled trial
    Neurology, 2011
    Co-Authors: Anthony H V Schapira, Robert A Hauser, Paolo Barone, Yoshikuni Mizuno, Laurence Salin, Nolwenn Juhel, O Rascol, Michael Busse, Werner Poewe
    Abstract:

    Background: In advanced Parkinson disease (PD), immediate-release Pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy. Methods: For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release Pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375–4.5 mg/day). The primary endpoint was a change in the Unified Parkinson9s Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout. Results: Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0–41.7) by an adjusted mean of −11.0 for extended-release Pramipexole and −12.8 for immediate-release Pramipexole vs −6.1 for placebo ( p = 0.0001 and p p = 0.0199 and p Conclusions: Extended-release Pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release Pramipexole compared with placebo. Classification of evidence: This study provides Class I evidence that the extended-release form of Pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD. Neurology ® 2011;77:767–774

Anthony H V Schapira - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and sustained efficacy of extended release Pramipexole in early and advanced parkinson s disease
    European Journal of Neurology, 2014
    Co-Authors: Robert A Hauser, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, O Rascol, Michael Busse, Mandy Fraessdorf, C Debieuvre, Werner Poewe
    Abstract:

    Background and purpose To assess the long-term safety and efficacy of Pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). Methods In two double-blind (DB) studies of early PD and one of advanced PD, active-treatment arms received Pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375–4.5 mg q.d.). Results Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0% were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to Pramipexole introduction, at −6.6 and −6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of Pramipexole (33 DB plus 80 OL) in early PD, and −11.5 and −9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. Conclusions These results support the long-term safety and efficacy of Pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

  • minimal clinically important difference in parkinson s disease as assessed in pivotal trials of Pramipexole extended release
    Parkinson's Disease, 2014
    Co-Authors: Robert A Hauser, Mark Forrest Gordon, Werner Poewe, Olivier Rascol, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, C Debieuvre, Mandy Frasdorf
    Abstract:

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of Pramipexole ER that included Pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (Pramipexole ER, Pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (Pramipexole ER, Pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  • Pramipexole in patients with early parkinson s disease proud a randomised delayed start trial
    Lancet Neurology, 2013
    Co-Authors: Anthony H V Schapira, Werner Poewe, Paolo Barone, Yoshikuni Mizuno, Michael P Mcdermott, Cynthia L Comella, Stefan Albrecht, Helen H Hsu, Dan Massey, Olivier Rascol
    Abstract:

    Summary Background In models of dopaminergic neuronal loss, the dopamine agonist Pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed Pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Methods Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30–79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or Pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to Pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Findings Of 535 patients, 261 were randomly assigned to receive Pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed Pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early Pramipexole group and 61 patients in the delayed Pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123 I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed Pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early Pramipexole and 179 (84%) patients given delayed Pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early Pramipexole group and 17 (8%) in the delayed Pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. Interpretation By clinical and neuroimaging measures, Pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6–9 months. The results do not support the hypothesis that Pramipexole has disease-modifying effects. Funding Boehringer Ingelheim GmbH.

  • efficacy and safety of extended versus immediate release Pramipexole in japanese patients with advanced and l dopa undertreated parkinson disease a double blind randomized trial
    Clinical Neuropharmacology, 2012
    Co-Authors: Yoshikuni Mizuno, Olivier Rascol, Anthony H V Schapira, Mitsutoshi Yamamoto, Sadako Kuno, Kazuko Hasegawa, Nobutaka Hattori, Tatsuro Kagimura, Akiko Sarashina, Paolo Barone
    Abstract:

    Objectives To compare the efficacy, safety, tolerability, and trough plasma levels of Pramipexole extended-release (ER) and Pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). Methods After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to Pramipexole ER once daily or Pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label Pramipexole ER, beginning with a 4-week dose-adjustment phase. Results Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with Pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to Pramipexole ER. Conclusions In L-dopa-treated patients, Pramipexole ER and Pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from Pramipexole IR to Pramipexole ER with no impact on efficacy.

  • extended release Pramipexole in early parkinson disease a 33 week randomized controlled trial
    Neurology, 2011
    Co-Authors: Werner Poewe, Robert A Hauser, Paolo Barone, Yoshikuni Mizuno, Laurence Salin, Monika Haaksma, Nolwenn Juhel, O Rascol, Anthony H V Schapira
    Abstract:

    Objective: To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist Pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) Pramipexole. Methods: This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to Pramipexole IR, Pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test Pramipexole ER noninferiority to Pramipexole IR based on a change in the Unified Parkinson9s Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed −3 points. Results: Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was −8.2 for ER and −8.7 for IR, a difference of −0.5 with a 95% CI of −2.3 to 1.3. Compared with placebo (n = 103), Pramipexole ER and Pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of Pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. Conclusions: As monotherapy for early PD, Pramipexole ER was noninferior to Pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. Classification of evidence: This study provides Class I evidence that Pramipexole ER is not inferior to Pramipexole IR in patients with early PD. Neurology ® 2011;77:759–766

Wolfgang H Oertel - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of Pramipexole and transdermal rotigotine in advanced parkinson s disease a double blind double dummy randomised controlled trial
    Lancet Neurology, 2007
    Co-Authors: Werner Poewe, Wolfgang H Oertel, Olivier Rascol, Niall Quinn, Eduardo Tolosa, Emilia Martignoni, Markus Rupp, Babak Boroojerdi
    Abstract:

    Summary Background Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson's disease. The aim of this trial—Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)—was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with Pramipexole in levodopa-treated patients with advanced Parkinson's disease and wearing-off type motor fluctuations. Methods In this randomised controlled trial, eligible participants were randomly assigned to receive either rotigotine (up to 16 mg/24 h as a transdermal patch), Pramipexole (up to 4·5 mg/day orally), or placebo for 6 months. Primary efficacy variables were absolute change in total hours "off" (assessed by home diaries) from baseline to end of study and responder rate (defined as the proportion of patients with ≥30% reduction in absolute off time per day). Analyses were done by intention to treat. This trial is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00244387. Findings 204 patients were randomly assigned to receive rotigotine, 201 to receive Pramipexole, and 101 to receive placebo; 427 (84%) completed the trial. The number of discontinuations in each group was similar; most were for adverse events. The mean dose of rotigotine was 12·95 mg/24 h (SD 3·54), the mean dose of Pramipexole was 3·1 mg/day (1·24). Mean absolute change in off time from baseline was −2·5 h (SE 0·20) with rotigotine, −2·8 h (0·20) with Pramipexole, and −0·9 h (0·29) with placebo. The absolute change in off time from baseline compared with placebo was −1·58 h (95% CI −2·27 to −0·90; p Interpretation In terms of change in absolute off time, rotigotine was non-inferior to Pramipexole. Continuous delivery of rotigotine as transdermal patches could offer similar efficacy to oral Pramipexole in patients with fluctuating Parkinson's disease over 6 months of treatment.

  • efficacy of Pramipexole in restless legs syndrome a six week multicenter randomized double blind study effect rls study
    Movement Disorders, 2007
    Co-Authors: Wolfgang H Oertel, Juergen Koester, Karin Stiasnykolster, Bettina Bergtholdt, Yngve Hallstrom, Jaan Albo, Lena Leissner, Thomas M Schindler, Juergen Reess
    Abstract:

    We evaluated the efficacy of Pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or Pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (Pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for Pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (Pramipexole) (P < 0.0001). For all secondary endpoints, Pramipexole showed superior results. Pramipexole was well tolerated throughout the study.

  • long term efficacy and safety of Pramipexole in advanced parkinson s disease results from a european multicenter trial
    Movement Disorders, 2005
    Co-Authors: Carsten J Moller, Wolfgang H Oertel, Jurgen Koster, Gianni Pezzoli, Leandro Provinciali
    Abstract:

    A double-blind, placebo-controlled study with a subsequent open-label phase was conducted in 354 patients with Parkinson's disease (PD) and motor fluctuations under individually adjusted therapy with levodopa. During the double-blind phase 174 patients received Pramipexole and 180 placebo. In agreement with previous studies, Pramipexole treatment improved UPDRS sum scores of parts II and III by 30% and off times by approximately 2.5 hours per day. Differences between the treatment groups became significant at a daily dose of 0.75 mg of Pramipexole dihydrochloride. We, furthermore, performed post hoc analyses with respect to resting tremor and depression. Patients with pronounced resting tremor derived a clear benefit from Pramipexole treatment compared with placebo. In addition, Pramipexole significantly improved the subitems motivation/initiative and depression in a subpopulation with increased Unified Parkinson's Disease Rating Scale I scores at the time of inclusion. There were 262 patients who were subsequently enrolled into the open-label study featuring a maximum duration of up to 57 months. Statistical analysis revealed good long-term efficacy and tolerability of Pramipexole. Overall, only a low prevalence of somnolence was found. In summary, this study provides additional level I evidence of the usefulness of Pramipexole, suggests a particular tremorlytic and a possible antidepressant action of this compound, and addresses for the first time its efficacy and safety during long-term administration in advanced PD.

  • Pramipexole in patients with parkinson s disease and marked drug resistant tremor a randomised double blind placebo controlled multicentre study
    Journal of Neurology Neurosurgery and Psychiatry, 2002
    Co-Authors: Oliver Pogarell, T Gasser, J J Van Hilten, S Spieker, S Pollentier, Diane E Meier, Wolfgang H Oertel
    Abstract:

    Objective: To compare the tremorlytic properties of Pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. Methods: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either Pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs. Results: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p<0.0001), corresponding to a difference in the mean percentage change of -34.7% in favour of Pramipexole. The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of Pramipexole compared with placebo. Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of -15.2% (95%CI -21.4 to -9.0) (p<0.0001), and a difference in the mean percentage change of -45.7% in favour of Pramipexole. The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study. The average daily Pramipexole dose during maintenance was 4.1 (SD 0.9) mg. Safety analysis showed an increased rate of fatigue, insomnia, nausea, abdominal pain, and headache under Pramipexole, comparable with previous studies. Conclusion: Pramipexole proved to be an effective agent for patients with Parkinson's disease and drug resistant tremor.

  • efficacy safety and tolerance of the non ergoline dopamine agonist Pramipexole in the treatment of advanced parkinson s disease a double blind placebo controlled randomised multicentre study
    Journal of Neurology Neurosurgery and Psychiatry, 1999
    Co-Authors: M M Pinter, Oliver Pogarell, Wolfgang H Oertel
    Abstract:

    Objectives—Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess eYcacy, safety, and tolerance. Methods—Seventy eight patients of either sex with advanced Parkinson’s disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with Pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of eYcacy was the change from baseline in the total score of the unified Parkinson’s disease rating scale (UPDRS) in the on “period” (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. Results—There was a significant improvement of the Pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under Pramipexole compared with 12.2% under placebo (p<0.001). Patients under Pramipexole reported an overall reduction in “oV” periods of 12%— resulting in 1.7 more hours “on” time a day—compared with an increase in “oV” periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under Pramipexole were fatigue, dyskinesia, and vivid dreams. Conclusion—Pramipexole administration is an eYcacious and well tolerated add on therapy in patients with advanced Parkinson’s disease with an improvement in activities of daily living, motor function, and treatment associated complications. (J Neurol Neurosurg Psychiatry 1999;66:436‐441)

Olivier Rascol - One of the best experts on this subject based on the ideXlab platform.

  • minimal clinically important difference in parkinson s disease as assessed in pivotal trials of Pramipexole extended release
    Parkinson's Disease, 2014
    Co-Authors: Robert A Hauser, Mark Forrest Gordon, Werner Poewe, Olivier Rascol, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, C Debieuvre, Mandy Frasdorf
    Abstract:

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of Pramipexole ER that included Pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (Pramipexole ER, Pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (Pramipexole ER, Pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  • Pramipexole in patients with early parkinson s disease proud a randomised delayed start trial
    Lancet Neurology, 2013
    Co-Authors: Anthony H V Schapira, Werner Poewe, Paolo Barone, Yoshikuni Mizuno, Michael P Mcdermott, Cynthia L Comella, Stefan Albrecht, Helen H Hsu, Dan Massey, Olivier Rascol
    Abstract:

    Summary Background In models of dopaminergic neuronal loss, the dopamine agonist Pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed Pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Methods Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30–79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or Pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to Pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Findings Of 535 patients, 261 were randomly assigned to receive Pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed Pramipexole (−0·4 points, 95% CI −2·2 to 1·4, p=0·65). 62 patients in the early Pramipexole group and 61 patients in the delayed Pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal 123 I-FP-CIT binding was −15·1% (SE 2·1) for early and −14·6% (2·0) for delayed Pramipexole (difference −0·5 percentage points, 95% CI −5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early Pramipexole and 179 (84%) patients given delayed Pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early Pramipexole group and 17 (8%) in the delayed Pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. Interpretation By clinical and neuroimaging measures, Pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6–9 months. The results do not support the hypothesis that Pramipexole has disease-modifying effects. Funding Boehringer Ingelheim GmbH.

  • efficacy and safety of extended versus immediate release Pramipexole in japanese patients with advanced and l dopa undertreated parkinson disease a double blind randomized trial
    Clinical Neuropharmacology, 2012
    Co-Authors: Yoshikuni Mizuno, Olivier Rascol, Anthony H V Schapira, Mitsutoshi Yamamoto, Sadako Kuno, Kazuko Hasegawa, Nobutaka Hattori, Tatsuro Kagimura, Akiko Sarashina, Paolo Barone
    Abstract:

    Objectives To compare the efficacy, safety, tolerability, and trough plasma levels of Pramipexole extended-release (ER) and Pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). Methods After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to Pramipexole ER once daily or Pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label Pramipexole ER, beginning with a 4-week dose-adjustment phase. Results Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with Pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to Pramipexole ER. Conclusions In L-dopa-treated patients, Pramipexole ER and Pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from Pramipexole IR to Pramipexole ER with no impact on efficacy.

  • randomized double blind multicenter evaluation of Pramipexole extended release once daily in early parkinson s disease
    Movement Disorders, 2010
    Co-Authors: Robert A Hauser, Olivier Rascol, Anthony H V Schapira, Paolo Barone, Yoshikuni Mizuno, Laurence Salin, Monika Haaksma, Nolwenn Juhel, Werner Poewe
    Abstract:

    The objective of this study was to evaluate the efficacy and safety of Pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A Pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of Pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with Pramipexole ER once daily, Pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the Pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the Pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the Pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the Pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the Pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the Pramipexole IR group (P = 0.0006). Adverse events more common with Pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as Pramipexole IR administered TID.

  • rationale for delayed start study of Pramipexole in parkinson s disease the proud study
    Movement Disorders, 2010
    Co-Authors: Anthony H V Schapira, Werner Poewe, Olivier Rascol, Paolo Barone, Yoshikuni Mizuno, Michael P Mcdermott, Cynthia L Comella, Stefan Albrecht, Kenneth Marek
    Abstract:

    Perhaps the most important unmet need in Parkinson's disease (PD) is the ability to slow or prevent progression of the neurodegeneration that underlies the motor and nonmotor features of this disorder. Pramipexole, a dopamine agonist used for the symptomatic treatment of PD, has demonstrated neuroprotective properties in laboratory studies. The Pramipexole On Underlying Disease (PROUD) study is a randomized, double-blind clinical trial evaluating the ability of Pramipexole to modify disease progression using a delayed-start design. PD patients (n = 535) with mean age 62.5 years, mean duration since diagnosis of 4.4 months, and mean total Unified Parkinson's disease Rating Scale (UPDRS) score of 24.5 were recruited. In Phase I, patients were randomly assigned to be titrated to 1.5 mg Pramipexole or placebo and maintained on study drug for 6-9 months. In Phase II, all patients were titrated to 1.5 mg Pramipexole and maintained on study drug until the end of the study at 15 months. No rescue medication was allowed in the protocol. The primary endpoint is the change in total UPDRS score (parts I-III) from baseline to 15 months. A range of secondary endpoints separately assess UPDRS subscales, quality of life, depression, and impulse control disorders. A sub-study examined dopamine transporter uptake scans at baseline and 15 months. The results of PROUD will provide insight into the potential for early versus delayed treatment with Pramipexole to modify motor outcome at 15 months in recently diagnosed PD patients.

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