Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease (VR040/2/003)
'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.
Drug: VR040/Aspirair® inhaler
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Clinic-Based, Phase IIa, Double-Blind, Placebo- Controlled, Ascending-Dose, Multicentre Study of Safety, Tolerability, Efficacy and Pharmacokinetics of VR040 in Parkinson's Disease|
- The maximum UPDRS 3 improvement from pre-dose to post-dose [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
- Time to improvement from 'off' to 'on' [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]Time to improvement from 'off' to 'on'.
- The duration of 'on' [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]The duration of 'on', the duration of time when the patient can function well.
- The proportion of patients converting to 'on' any time after treatment administration. [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]The proportion of patients converting to 'on' any time after treatment administration.
- Safety variables [ Time Frame: 90minutes ] [ Designated as safety issue: Yes ]Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.
|Study Start Date:||March 2007|
|Study Completion Date:||July 2009|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
Active Comparator: VR040/Aspirair® inhaler
VR040 was administered as an inhaled dry powder, in a dosage of 1.5, 2.3, 3.0 and 4.0mg, single dose given at each dose level.
Drug: VR040/Aspirair® inhaler
Dry Powder inhaled apomorphine
Other Name: Inhaled apomorphine
Placebo Comparator: Placebo
Placebo was administered as an inhaled dry powder, matching to active comparator at dosages of 1.5, 2.3, 3.0 and 4.0mg, single dose given at each dose level.
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.
|Neurology Clinical Military Medical Academy, Crnotravska 17|
|Belgrade, Serbia, 11 000|
|Institute of Neurology Clinical Center Serbia Dr Subotica 6|
|Belgrade, Serbia, 11000|
|University Hospital, Wales|
|Cardiff, United Kingdom, CF14 4XW|
|Department of Neurology, Southern General Hospital|
|Glasgow, United Kingdom, G51 4TF|
|The Walton Centre|
|Liverpool, United Kingdom, L9 7LJ|
|Llandudno, United Kingdom, LL30 1LB|
|Newark, United Kingdom, NG24 4DE|
|Neurology Dept, Radcliffe Infirmary|
|Oxford, United Kingdom, OX2 6HE|
|Essex Neurosciences, UnitOld Church Hospital, Essex|
|Romford Essex, United Kingdom, RM7 0BE|
|Principal Investigator:||Donald Grosset, MD||South Glasgow NHS Hospitals|