Several new studies presented at the AAN Annual Meeting last month explored the potential role of pramipexole ER (Mirapex ER, Boehringer Ingelheim), currently under regulatory review, in patient care. Data support the efficacy and convenience of the formulation.
For patients with early PD, pramipexole IR improves symptoms and can delay the need for levodopa. However, pramipexole IR is administered TID, and a once-a-day ER formulation would increase patient convenience and could improve patient compliance, researchers believe. A double-blind trial pitted pramipexole ER (optimized at 0.375-4.5mg QD) and IR (optimized at 0.125-1.5mg TIS) versus placebo, with all subjects having PD Hoehn-Yahr stage I-III. At 33 weeks, 84 patients remained (35 ER, 31 IR, 18 placebo). In both pramipexole ER and IR groups, "efficacy was maintained at 33 weeks compared with 18 weeks, while placebo patients worsened."
Maintenance of efficacy was predefined as less than or equal to 15 percent worsening at week 33 compared to week 18. Efficacy was also judged by responder rate of "much" or "very much" improved on the Clinical Global Impression-Improvement and Patient Global Impression-Improvement scales.
Neurologists will need to know how to best transition patients from IR to ER formulations if the latter is approved. Researchers (P06.152) found that 84.5 percent of early PD patients successfully switched from pramipexole IR to ER in overnight switching. The nine-week double-blind, double-dummy, randomized, parallel-group study was conducted on 156 patients with early PD on stable doses of pramipexole IR (2.7 0.9 mg±0.9mg/day). The patients were randomized overnight to ER or IR (2:1 ratio) at unchanged doses; dose adaptation was allowed at week four and five if UPDRS II+III was >15 percent worse than baseline. Primary efficacy endpoint was the proportion of patients successfully switched, no worsening of UPDRS II+III >15 percent from baseline, and no adverse effects leading to withdrawal. The primary analysis used one-sided non-inferiority statistical test at five percent significance and non-inferiority margin of 15 percent.
Pramipexole ER was found to be superior to placebo and comparable in efficacy to IR at the same dosage, according to another study (S43.003). Researchers designed an 18-week, randomized, double-blind trial of ER (0.375-4.5mg qd) and IR (0.125-1.5mg tid) versus placebo. All of the patients had PD at Hoehn-Yahr stage I-III (diagnosed within the past five years), no prior levodopa exposure totaling >3 months, no l-dopa within the past eight weeks, and no dopamine agonists within the prior four weeks.
Of the 253 patients who completed the study, 102 were in the ER group, 101 in the IR, and 50 controls. At week 18, mean UPDRSII+III change (adjusted for country, treatment group, and baseline) was -8.1 for ER and -7.5 for IR, versus 2.7 for placebo (P=.0010 and P=.006). CGI-I responder rate was 37 percent for ER and 48 percent for IR, versus 12 percent for placebo (P=.0040 and P=.1207).
According to reports, approval of the ER formulation could come within a few months. However, in the next year, generic formulations of standard pramipexole could come to market, potentially challenging patients to weigh costs over convenience