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


OBJECTIVE
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.
Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK.
Katherine A
KA
Grosset
Naveed
N
Malek
Frazer
F
Morgan
Donald G
DG
Grosset
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D057915:Drug Substitution; D005260:Female; D006699:Home Care Services; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D001058:Apomorphine