'Off periods' where people with Parkinson's disease are slow, stiff and unable to function are disabling, and a treatment which can converts people to a "on", good, able to function state would be extremely useful. We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a clinic-based study in this setting.
Background: 'Off' periods increase as Parkinson's disease 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 clinic-based Phase II study. Of 48 patients recruited at 9 sites, 47 were randomized 2:1 inhaled apomorphine:placebo. Respirable doses (drug predicted to reach the lung) ascending through 1.5mg, 2.3mg, 3.0mg, and 4.0mg until efficacy was achieved, were administered to patients in a practically defined 'off' state. The primary endpoint was the response in unified Parkinson's disease 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 pharmacokinetics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
47
Dry Powder inhaled apomorphine
Neurology Clinical Military Medical Academy, Crnotravska 17
Belgrade, Serbia
Institute of Neurology Clinical Center Serbia Dr Subotica 6
Belgrade, Serbia
University Hospital, Wales
Cardiff, United Kingdom
Department of Neurology, Southern General Hospital
The maximum UPDRS 3 improvement from pre-dose to post-dose
The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
Time frame: 90 minutes
Time to improvement from 'off' to 'on'
Time to improvement from 'off' to 'on'.
Time frame: 90 minutes
The duration of 'on'
The duration of 'on', the duration of time when the patient can function well.
Time frame: 90 minutes
The proportion of patients converting to 'on' any time after treatment administration.
The proportion of patients converting to 'on' any time after treatment administration.
Time frame: 90 minutes
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Glasgow, United Kingdom
The Walton Centre
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Llandudno Hospital
Llandudno, United Kingdom
Newark Hospital
Newark, United Kingdom
Neurology Dept, Radcliffe Infirmary
Oxford, United Kingdom
Essex Neurosciences, UnitOld Church Hospital, Essex
Romford Essex, United Kingdom