Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease (VR040/2/003)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01693081
|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|