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 receivinglevodopa 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 Parkinson's 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.
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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 Parkinson's 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.
Authors: Tamara Pringsheim; Gregory S Day; Don B Smith; Alex Rae-Grant; Nicole Licking; Melissa J Armstrong; Rob M A de Bie; Emmanuel Roze; Janis M Miyasaki; Robert A Hauser; Alberto J Espay; Justin P Martello; Julie A Gurwell; Lori Billinghurst; Kelly Sullivan; Michael S Fitts; Nicholas Cothros; Deborah A Hall; Miriam Rafferty; Lynn Hagerbrant; Tara Hastings; Mary Dolan O'Brien; Heather Silsbee; Gary Gronseth; Anthony E Lang Journal: Neurology Date: 2021-11-16 Impact factor: 9.910