Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease

• Published in: European Journal of Neurology Vol. 21; no. 5; pp. 736 - 743
• Main Authors: Hauser, R. A., Schapira, A. H. V., Barone, P., Mizuno, Y., Rascol, O., Busse, M., Debieuvre, C., Fraessdorf, M., Poewe, W.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2014; Wiley; John Wiley & Sons, Inc; BlackWell Publishing Ltd
• Subjects: Aged; Aged; Antiparkinson Agents; Benzothiazoles; Disorders of Excessive Somnolence; Disruptive, Impulse Control, and Conduct Disorders; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Middle Aged; Parkinson Disease; Severity of Illness Index; Time Factors; Antiparkinson Agents; Antiparkinson Agents - therapeutic use; Benzothiazoles; Benzothiazoles - therapeutic use; Disorders of Excessive Somnolence; Disorders of Excessive Somnolence - etiology; Disruptive, Impulse Control, and Conduct Disorders; Disruptive, Impulse Control, and Conduct Disorders - chemically induced; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Drug Delivery Systems - adverse effects; Drug Delivery Systems - methods; Drug therapy; Dyskinesia, Drug-Induced; Dyskinesia, Drug-Induced - etiology; Female; Follow-Up Studies; Humans; Male; Middle Aged; once daily; oral formulation; Original; Original Articles; Parkinson Disease; Parkinson Disease - drug therapy; Parkinson's disease; Pramipexole; Severity of Illness Index; Time Factors; unified Parkinson's disease rating scale
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.12375

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.