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.
RCT Entities:
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.
Authors: Adam Strzelczyk; Laurent M Willems; Ricardo Kienitz; Lara Kay; Isabelle Beuchat; Sarah Gelhard; Sophie von Brauchitsch; Catrin Mann; Alexandra Lucaciu; Jan-Hendrik Schäfer; Kai Siebenbrodt; Johann-Philipp Zöllner; Susanne Schubert-Bast; Felix Rosenow Journal: CNS Drugs Date: 2022-08-16 Impact factor: 6.497
Authors: Eva Thijssen; Jonas den Heijer; David Puibert; Laurence Moss; Mingzu Lei; David Hasegawa; Kyo Keum; Ken Mochel; Mohammed Ezzeldin Sharaf; Tom Alfredson; Wenxiang Zeng; Emilie van Brummelen; Tatjana Naranda; Geert Jan Groeneveld Journal: Mov Disord Date: 2022-01-20 Impact factor: 9.698