A randomized study of rotigotine dose response on 'off' time in advanced Parkinson's disease.
J Parkinsons Dis
; 4(3): 361-73, 2014.
Article
em En
| MEDLINE
| ID: mdl-24643203
ABSTRACT
BACKGROUND:
Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established.OBJECTIVE:
This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h.METHODS:
Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses of levodopa) were randomized 11111 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'.RESULTS:
409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily 'off' times (h/day) were placebo 6.4 (±2.5), rotigotine 2-8 mg/24 h 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (±SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (±0.28) with rotigotine 8 mg/24 h, and -1.5 (±0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age.CONCLUSIONS:
The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Tetra-Hidronaftalenos
/
Tiofenos
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article