Safety and tolerability of pardoprunox, a new partial dopamine agonist, in a randomized, controlled study of patients with advanced Parkinson's disease.
OBJECTIVE
To investigate the safety and tolerability of pardoprunox (SLV308), a novel partial dopamine agonist, as an adjunct to levodopa in patients with advanced Parkinson's disease, using two titration schedules.


METHODS
Patients were randomized to pardoprunox (n = 51) or placebo (n = 11). Pardoprunox was titrated to the highest tolerated dose (range, 0.3-42 mg/day) over 7 weeks, using a gradual dose escalation without intermediate steps (group 1) or with intermediate steps (group 2).


RESULTS
The cumulative drop-out rate was greater in group 1 (without intermediate steps, 56.0%) than in group 2 (with intermediate steps, 34.6%), or with placebo (9.1%). In group 2, doses up to 18 mg/day were well tolerated with a cumulative drop-out rate of 7.7% (2/26) and a drop-out rate due to adverse events of 4.0% (1/26). The most common adverse events reported were nausea, vomiting, headache, and dizziness. There was a trend for reduced OFF time (p = 0.054) in the combined pardoprunox group compared to placebo.


CONCLUSIONS
The pardoprunox safety and tolerability profile as an adjunct to levodopa was improved using a gradual titration schedule that included intermediate dose steps. Using this titration, doses up to 18 mg/day were well tolerated.
Hauser
R A
RA
University of South Florida, Tampa, FL 33606, USA. rhauser@hsc.usf.edu
Bronzova
J
J
Sampaio
C
C
Lang
A E
AE
Rascol
O
O
Theeuwes
A
A
van de Witte
S V
SV
D000368:Aged; D001583:Benzoxazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010300:Parkinson Disease / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
D001583:Benzoxazoles; D018491:Dopamine Agonists; D010879:Piperazines; D007980:Levodopa; C480679:pardoprunox