Inhaled dry powder apomorphine (VR040) for 'off ' periods in Parkinson's disease: an in-clinic double-blind dose ranging study

Acta Neurol Scand. 2013 Sep;128(3):166-71. doi: 10.1111/ane.12107. Epub 2013 Mar 26.


Background: 'Off' periods increase as Parkinson's disease (PD) progresses and the benefits of standard therapy wane. Subcutaneous apomorphine rescues 'off' periods, but patient self-injection and adverse cutaneous effects are sometimes problematic.

Methods: We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a double-blind clinic-based Phase II study. Of 48 patients recruited at nine sites, 47 were randomized 2:1 inhaled apomorphine/placebo. Respirable doses (drug predicted to reach the lung), ascending through 1.5, 2.3, 3.0 and 4.0 mg until efficacy was achieved, were administered to patients in a practically defined 'off' state. The primary endpoint was the response in unified PD rating scale Part 3 (UPDRS 3), at the highest dose received by the patient. Secondary endpoints included time to 'on', the proportion of patients converting from 'off' to 'on', and duration of 'on'.

Results: In the 47 intent-to-treat patients with PD, mean age 60.6 years, the mean UPDRS 3 improvement was significantly greater for VR040 at 26.8 points (standard deviation 12.0), vs 14.9 (16.3) for placebo (treatment difference 11.6, 95% confidence interval 2.3-20.9, P = 0.016). Rapid apomorphine absorption (2-7 min) translated to rapid (mean 10 min) reversal from the 'off' state. Adverse effects did not differ between VR040 and placebo; no patient discontinued due to an adverse event; one serious adverse event (constipation) in the VR040 group was considered unrelated to trial medication.

Conclusions: Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability.

Keywords: Parkinson's disease; apomorphine; motor fluctuations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Apomorphine / administration & dosage*
  • Apomorphine / pharmacokinetics
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / pharmacokinetics
  • Double-Blind Method
  • Dry Powder Inhalers / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Retrospective Studies
  • Severity of Illness Index
  • Time Factors


  • Dopamine Agonists
  • Apomorphine