Phase IIa randomized double-blind, placebo-controlled study of inhaled apomorphine as acute challenge for rescuing ‘off’ periods in patients with established Parkinson's disease
- See editorial by Perez-Lloret on page 1427
Correspondence: N. Malek, Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK (tel.: 00044 141 2012486; fax: 0044 141 2327626; e-mail: firstname.lastname@example.org).
Background and purpose
In this first study of inhaled apomorphine (VR040) in patients with Parkinson's disease, the primary objective was to find the minimum efficacious dose of apomorphine that was useful in rescuing patients during ‘off’ periods. Safety, tolerability and pharmacokinetics of inhaled apomorphine were assessed during the study.
A double-blind, placebo-controlled, randomized trial of three escalating single doses of inhaled apomorphine (0.2, 0.5 and 0.8 mg fine particle dose) versus placebo (3 : 1 active:placebo) was performed. Parkinson's motor severity assessments by a clinician, and disease state assessment by the patient, were performed at baseline during an ‘off’ state, and at specified times after test drug administration. Safety assessments (including vital signs, electrocardiogram and forced expiratory volume) were performed, and plasma apomorphine levels measured.
All 24 patients completed the study, and considering the three dose levels together, inhaled apomorphine did not significantly increase the proportion of patients switching from ‘off’ to ‘on’ (0/6 at 0.2 mg, 3/6 at 0.5 mg and 2/6 at 0.8 mg vs. 1/6 for placebo), or decrease the time from ‘off’ to ‘on’ post-treatment (10 min for 0.5 mg, 40 min for 0.8 mg, vs. 20 min for placebo). However, there was a suggestion of benefit at the higher doses (5/12 switched ‘on’ at the 0.5 or 0.8 mg doses, vs. 1/6 for placebo). There were no serious adverse events and treatment was well tolerated. Peak plasma concentration was 1–3 min post-dose, and plasma level dose proportionality was observed.
Inhaled apomorphine was safe and well tolerated at the doses tested for an acute challenge to rescue ‘off’ periods, but efficacy at these doses was limited. A follow-up study at higher doses is appropriate given these initial findings.