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.
OBJECTIVE
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.
Department of Neuroregenerative Medicine, Kitasato University School of Medicine, Kanagawa, Japan. y_mizuno@juntendo.ac.jp
Yoshikuni
Y
Mizuno
Mitsutoshi
M
Yamamoto
Sadako
S
Kuno
Kazuko
K
Hasegawa
Nobutaka
N
Hattori
Tatsuro
T
Kagimura
Akiko
A
Sarashina
Olivier
O
Rascol
Anthony H V
AH
Schapira
Paolo
P
Barone
Robert A
RA
Hauser
Werner
W
Poewe
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology; D052160:Benzothiazoles / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution / Q000379:methods; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology*; D000077487:Pramipexole; D012720:Severity of Illness Index; D016896:Treatment Outcome
D052160:Benzothiazoles; D003692:Delayed-Action Preparations; D007980:Levodopa; D000077487:Pramipexole