A Small-scale Phase IV Clinical Trial of Two Non-ergot Dopamine Agonists: Slowly Switching from Ropinirole to Pramipexole in Patients with Parkinson''s Disease

• Main Authors: Shin-Chia Tsai, 蔡欣佳
• Other Authors: 劉景平
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/59967084075455423785

碩士 === 臺北醫學大學 === 藥學研究所 === 97 === Background: Dopamine receptor agonists (DAs), especially D2 subtype could be used as monotherapy in patients with early Parkinson’s disease (PD) or adjunctive therapy to L-DOPA in advanced PD with motor complications. DAs are divided into ergot and non-ergot agents. Recent studies indicate that taking high dosages of ergot-derived DAs are associated with valvular heart disease. Therefore, switching from ergot to non-ergot DAs to prevent such adverse drug reactions is the main research goal of many clinical trials. To the best of our knowledge, very few studies have investigated the direct switch between non-ergot DAs. The conversion factor between ropinirole and pramipexole is calculated indirectly and thus the published values are inconsistent. Pramipexole is a non-ergot DA, which has more bioavailability (> 90% vs. 50%) and longer half-life (8~12 hours vs. 6 hours) than ropinirole. Moreover, pramipexole is not metabolized by cytochrome P450 enzymes and it does not have interactions with this enzyme system; pramipexole is primarily eliminated through the kidneys. Furthermore, pramipexole has been shown to have relatively high affinity for the D3 receptor and putative neuroprotective effects. These properties of pramipexole may lead to additional antidepressant action. Objectives: The mission of this study was to determine the conversion factor between two non-ergot DAs, ropinirole (Requip®) and pramipexole (Mirapex®) in Taiwanese PD patients and evaluated the possible antidepressant effect of pramipexole. Methods: In this prospective open-label pilot study, a small-scale phase IV clinical trial of two non-ergot DAs was carried out at Taipei Medical University Hospital, during the period of June, 2008 to June, 2009. Patients with PD (aged 45 to 80 years old) had taken stable doses of ropinirole with or without L-DOPA (Madopar®) for at least 28 days were recruited. After stopping ropinirole treatment, patients were switched to pramipexole with a log escalating dose until reaching the optimal motor control. The effective dosage of pramipexole was kept unchanged in the three-month maintenance period. This paired design would minimize confounding factors and thus a small sample size was needed for studying the primary and secondary endpoints. The primary endpoint was to determine the conversion factor between ropinirole and pramipexole at the end of the 12-week maintenance period, assessed by the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III). The secondary outcomes included changes in the Beck Depression Inventory-Second Edition (BDI-II) and the 39-item Parkinson''s Disease Questionnaire (PDQ-39) scores during the study period. Patient’s satisfaction with pramipexole by Treatment Satisfaction Questionnaire for Medication (TSQM) and safety of the switch were also evaluated. Results: A total of 17 PD patients were recruited and 10 of them completed the 12-week maintenance course. The pre-switch dosage of ropinirole was 3.1 mg/day and the post-switch maintenance dosage of pramipexole was 0.6 mg/day. The dosage of pramipexole was lower than that in the western countries. The conversion factor was 5.6±2.8 (n=10), that was directly derived from each patient’s paired data. The UPDRS-III score showed a significant decrease from 22.4±10.2 to 15.8±6.6 (p<0.05), reflecting an improvement in motor performance. There was no significant change in the BDI-II during the switch period. However, a significant difference in the PDQ-39 summary index was obtained after the second month of the maintenance period. There were significant changes in both effectiveness and global satisfaction scores of the TSQM simultaneously. The most common adverse events while switching to pramipexole were dizziness and constipation. Conclusions: In summary, a directly slow switch from ropinirole to pramipexole at a conversion factor of 5.6 showed the motor improvement after a 12-week maintenance period. This factor derived from the present study could be useful in developing a protocol of an overnight switch from ropinirole to pramipexole in Taiwanese patients with PD.