Parkinson’s Disease Off Time Reduced With Apomorphine

elderly hands resting on knee
elderly hands resting on knee
A 150-year-old drug, apomorphine, may reduce off time in patients with Parkinson's disease.
The following article is part of live conference coverage from the 2017 American Academy of Neurology (AAN) annual meeting in Boston, Massachusetts. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAN 2017.

BOSTON — Subcutaneous infusion of apomorphine (Britannia Pharmaceuticals), a 150-year-old drug, was shown to reduce off time in patients with Parkinson’s disease without increasing the occurrence of dyskinesia in those with motor fluctuations that cannot be controlled with current standard-of-care treatment.1

“If [persons] with Parkinson’s disease can reduce their off times, that can have a great impact on their everyday life,” study investigator Regina Katzenschlager, MD, of Danube Hospital in Vienna, Austria, said in a statement.2 “In some patients in the trial, the insecurity of unpredictable periods of incapacity was completely alleviated.”

For the first-of-its-kind, prospective, double-blind, placebo-controlled, phase 3 TOLEDO trial, data from which were presented at the American Academy of Neurology (AAN) 2017 Annual Meeting, Dr Katzenschlager and colleagues enrolled 106 patients with Parkinson’s disease from 23 centers in 7 countries. Patients were randomly assigned to receive apomorphine (n=53) during waking time (16 ± 2 hours; ≤8 mg/h) or placebo saline infusion (n=53) using the same pump system.

During the first 4 weeks, the researchers modified hourly infusion flow rate and concomitant antiparkinsonian medication dose based on efficacy and tolerability.

Absolute change in off time from baseline to week 12, which was based on patient diaries, served as the primary end point measure.

Results revealed that apomorphine significantly reduced off time between baseline and week 12 compared with placebo (-2.47 vs -0.58 hours), resulting in a treatment difference between groups of -1.89 hours (95% CI, -3.16 to -0.62; P =.0025).

The researchers also found that the off-time reduction with apomorphine occurred within the first week of treatment, was sustained over 12 weeks, and yielded a significant increase in on time without dyskinesia.

In other data, patients receiving apomorphine reported higher Patient Global Impression of Change scores compared with those receiving placebo (P <.001) at 12 weeks. Furthermore, apomorphine was generally well tolerated, and no unexpected adverse events were reported.

“It is our hope that these findings confirming the efficacy of apomorphine infusion will encourage doctors in the United States to offer this treatment to their patients and assess its efficacy in their own clinical practice,” Dr Katzenschlager said.

Disclosure: The study was supported by Britannia Pharmaceuticals.

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  1. Katzenschlager R, Poewe W, Rascol O, et al. Double-blind, randomized, placebo-controlled, Phase III study (TOLEDO) to evaluate the efficacy of apomorphine subcutaneous infusion in reducing OFF time in Parkinson’s disease patients with motor fluctuations not well controlled on optimized medical treatment. Presented at: 2017 American Academy of Neurology Annual Meeting. April 22-28, 2017; Boston, MA.
  2. 150-year-old drug may provide ‘off’ time relief for people with advanced Parkinson’s disease [news release]. Boston, MA: American Academy of Neurology newsroom; April 19, 2017.