Inhaled apomorphine in patients with 'on-off' fluctuations: a randomized, double-blind, placebo-controlled, clinic and home based, parallel-group study

Grosset, K. A., Malek, N., Morgan, F. and Grosset, D. (2013) Inhaled apomorphine in patients with 'on-off' fluctuations: a randomized, double-blind, placebo-controlled, clinic and home based, parallel-group study. Journal of Parkinson's Disease, 3(1), pp. 31-37. (doi:10.3233/JPD-120142) (PMID:23938309)

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Abstract

Background: In later stages of Parkinson's disease, treatment of ‘off’ periods with subcutaneous apomorphine is helpful but requires injection; inhaled apomorphine would be potentially more convenient. Objectives: To identify optimal efficacy, safety and tolerability for inhaled apomorphine in reversing Parkinson's disease ‘off’ periods. Methods: A randomized, double-blind, 2:1 active:placebo, parallel-group, ascending dose titration study was conducted at 16 centres in 3 countries. Inhaled apomorphine was administered under observation, at escalating fine particle doses of 1.5, 2.5, 3.5 and 4.5 mg. This was followed by at-home patient self-treatment for 2 to 4 weeks, assessed from ‘on-off’ diaries. Results: In 55 patients, mean age 65.6 years (range 47–79), mean disease duration 12 years (range 5–22), the mean improvement in the unified PD rating scale part 3 (UPDRS 3) was significantly greater for apomorphine (mean dose 2.3 mg) at 19.5 (standard deviation 13.6) than for placebo at 9.9 (9.6), least squares mean difference 8.4 (95% confidence interval 1.2 to 15.5, p = 0.023). During at-home testing, mean ‘off’ time per day was reduced by 139.8 minutes (standard deviation 149.6) for apomorphine versus 68.0 (108.6) minutes for placebo, least squares mean difference not significant at 100.5 minutes (95% confidence interval −12.0 to 212.9, p = 0.078). The onset of action was faster for apomorphine (mean 8.1 SD 6.2 minutes) than placebo (mean 13.1 SD 6.6 minutes) (p < 0.0001). Reversal of ‘off’ episodes was significantly more likely for episodes treated with apomorphine than those treated with placebo: apomorphine 64.6% SD 32.3 of episodes versus placebo 11.1% SD 15.3 (p < 0.0001). During at-home treatment, 36% of apomorphine and 20% of placebo patients experienced adverse events. Conclusions: Inhaled apomorphine in the dose range 1.5 to 4.5 mg, significantly improved UPDRS 3 scores in the clinic, and aborted a greater proportion of ‘off’ periods at-home, compared to placebo. However, daily ‘off’ time was not significantly reduced by the use of inhaled apomorphine.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Grosset, Dr Donald and Grosset, Dr Katherine
Authors: Grosset, K. A., Malek, N., Morgan, F., and Grosset, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Parkinson's Disease
Publisher:IOS Press
ISSN:1877-7171
ISSN (Online):1877-718X

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