Inhaled dry powder apomorphine (VR040) for ‘off ’ periods in Parkinson's disease: an in-clinic double-blind dose ranging study
Article first published online: 26 MAR 2013
© 2013 John Wiley & Sons A/S
Acta Neurologica Scandinavica
Volume 128, Issue 3, pages 166–171, September 2013
How to Cite
Inhaled dry powder apomorphine (VR040) for ‘off’ periods in Parkinson's disease: an in-clinic double-blind dose ranging study. Acta Neurol Scand 2013: 128: 166–171. © 2013 John Wiley & Sons A/S., , , .
- Issue published online: 16 AUG 2013
- Article first published online: 26 MAR 2013
- Manuscript Accepted: 11 JAN 2013
- Vectura plc
- Parkinson's disease;
- motor fluctuations
‘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.
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’.
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.
Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability.