Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease (VR040/2/003)
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VR040/Aspirair® inhaler
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, inhaled apomorphine, convert "off" to "on"
Eligibility Criteria
Inclusion Criteria:
- Male or female between 30 and 90 years old with idiopathic PD for at least 5 years.
- Voluntary written informed consent provided.
- Willing and able to comply with study procedures.
- Fulfilled steps 1 and 2 of the UK Brain Bank Criteria.
- Classified as Hoehn and Yahr Stage II to IV in "on" state.
- Motor fluctuations with recognisable "off" periods in control of motor symptoms, as assessed by the Motor Fluctuation Questionnaire.
- Optimised oral therapy.
- Dopaminergic responsiveness as defined by ≥ 30% improvement(reduction) in UPDRS III score compared with pre-dose value.
Exclusion Criteria:
- Participated in a trial with an investigational product within prior 3 months.
- Serious uncontrolled disease including serious psychological disorders.
- Previous intolerance to apomorphine.
- Previous significant complication from oral dopamine agonist therapy
- Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method (eg, barrier, intrauterine device, abstinence).
- Known HIV or active chronic hepatitis B or C infection.
- Any clinically significant abnormality following review of screening observations
- Patients who, in the Investigator's opinion, were unsuitable for the study for any reason.
- Major ECG abnormalities.
- Patients with a FEV1 ≤ 65% predicted.
- Patients showing a postural decrease in systolic blood pressure (BP) of ≥20 mm Hg or showing significant clinical symptoms associated with orthostatic hypotension.
- Patients with persistent arterial hypotension, with average systolic readings of ≤110 mm Hg.
Patients with persistent elevation of BP, with average systolic readings of ≥160 mm Hg.
or average diastolic readings of ≥100 mm Hg.
- Patients taking apomorphine at any time during these study visits, anabolic steroids,traditional antipsychotics (unless low dose) and vasodilators other than for the treatment of hypertension. The following atypical antipsychotics were permitted: Quetiapine (up to and including 50 mg per day), risperidone (up to and including 1 mg per day) and olanzapine (up to and including 2.5 mg per day).
- Patients taking agents of the 5HT3 antagonist class including ondansetron, granisetron,dolasetron, palonosetron and alosetron.
- Patients with existing cancer and those in remission for less than 5 years.
- Patients with evidence (as ascertained from examination, tests or history) to indicate cardiovascular, gastrointestinal tract, liver, kidney, central nervous system, pulmonary system or bone marrow disorders that in the Investigator's opinion compromised patient safety.
- Patients who were known non-responders to apomorphine treatment for "off" episodes(eg, in previous challenge tests or trials).
- Patients with a history of drug or alcohol abuse in the 12 months prior to entry.
- Patients with a history of clinically significant allergies to VR040 formulation constituents (including lactose and opioids) and domperidone.
- Patients with signs or symptoms suggestive of psychosis, dementia, "Parkinson-plus" syndromes or unstable systemic disease.
- Patients with history of stroke, seizure or other neurological conditions.
- Patients with dyskinesia rated 4 in Item 32 of UPDRS IV assessment at Screening(dyskinesia present ≥76% of a waking day).
Sites / Locations
- Neurology Clinical Military Medical Academy, Crnotravska 17
- Institute of Neurology Clinical Center Serbia Dr Subotica 6
- University Hospital, Wales
- Department of Neurology, Southern General Hospital
- The Walton Centre
- Llandudno Hospital
- Newark Hospital
- Neurology Dept, Radcliffe Infirmary
- Essex Neurosciences, UnitOld Church Hospital, Essex
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
VR040/Aspirair® inhaler
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Time to improvement from 'off' to 'on'
Time to improvement from 'off' to 'on'.
The duration of 'on'
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.
The proportion of patients converting to 'on' any time after treatment administration.
Full Information
NCT ID
NCT01693081
First Posted
September 21, 2012
Last Updated
September 25, 2012
Sponsor
South Glasgow University Hospitals NHS Trust
Collaborators
Vectura Limited
1. Study Identification
Unique Protocol Identification Number
NCT01693081
Brief Title
Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease
Acronym
VR040/2/003
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
South Glasgow University Hospitals NHS Trust
Collaborators
Vectura Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
'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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's disease, inhaled apomorphine, convert "off" to "on"
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VR040/Aspirair® inhaler
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
VR040/Aspirair® inhaler
Other Intervention Name(s)
Inhaled apomorphine
Intervention Description
Dry Powder inhaled apomorphine
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
The maximum UPDRS 3 improvement from pre-dose to post-dose
Description
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
Secondary Outcome Measure Information:
Title
Time to improvement from 'off' to 'on'
Description
Time to improvement from 'off' to 'on'.
Time Frame
90 minutes
Title
The duration of 'on'
Description
The duration of 'on', the duration of time when the patient can function well.
Time Frame
90 minutes
Title
The proportion of patients converting to 'on' any time after treatment administration.
Description
The proportion of patients converting to 'on' any time after treatment administration.
Time Frame
90 minutes
Other Pre-specified Outcome Measures:
Title
Safety variables
Description
Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.
Time Frame
90minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female between 30 and 90 years old with idiopathic PD for at least 5 years.
Voluntary written informed consent provided.
Willing and able to comply with study procedures.
Fulfilled steps 1 and 2 of the UK Brain Bank Criteria.
Classified as Hoehn and Yahr Stage II to IV in "on" state.
Motor fluctuations with recognisable "off" periods in control of motor symptoms, as assessed by the Motor Fluctuation Questionnaire.
Optimised oral therapy.
Dopaminergic responsiveness as defined by ≥ 30% improvement(reduction) in UPDRS III score compared with pre-dose value.
Exclusion Criteria:
Participated in a trial with an investigational product within prior 3 months.
Serious uncontrolled disease including serious psychological disorders.
Previous intolerance to apomorphine.
Previous significant complication from oral dopamine agonist therapy
Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method (eg, barrier, intrauterine device, abstinence).
Known HIV or active chronic hepatitis B or C infection.
Any clinically significant abnormality following review of screening observations
Patients who, in the Investigator's opinion, were unsuitable for the study for any reason.
Major ECG abnormalities.
Patients with a FEV1 ≤ 65% predicted.
Patients showing a postural decrease in systolic blood pressure (BP) of ≥20 mm Hg or showing significant clinical symptoms associated with orthostatic hypotension.
Patients with persistent arterial hypotension, with average systolic readings of ≤110 mm Hg.
Patients with persistent elevation of BP, with average systolic readings of ≥160 mm Hg.
or average diastolic readings of ≥100 mm Hg.
Patients taking apomorphine at any time during these study visits, anabolic steroids,traditional antipsychotics (unless low dose) and vasodilators other than for the treatment of hypertension. The following atypical antipsychotics were permitted: Quetiapine (up to and including 50 mg per day), risperidone (up to and including 1 mg per day) and olanzapine (up to and including 2.5 mg per day).
Patients taking agents of the 5HT3 antagonist class including ondansetron, granisetron,dolasetron, palonosetron and alosetron.
Patients with existing cancer and those in remission for less than 5 years.
Patients with evidence (as ascertained from examination, tests or history) to indicate cardiovascular, gastrointestinal tract, liver, kidney, central nervous system, pulmonary system or bone marrow disorders that in the Investigator's opinion compromised patient safety.
Patients who were known non-responders to apomorphine treatment for "off" episodes(eg, in previous challenge tests or trials).
Patients with a history of drug or alcohol abuse in the 12 months prior to entry.
Patients with a history of clinically significant allergies to VR040 formulation constituents (including lactose and opioids) and domperidone.
Patients with signs or symptoms suggestive of psychosis, dementia, "Parkinson-plus" syndromes or unstable systemic disease.
Patients with history of stroke, seizure or other neurological conditions.
Patients with dyskinesia rated 4 in Item 32 of UPDRS IV assessment at Screening(dyskinesia present ≥76% of a waking day).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald Grosset, MD
Organizational Affiliation
South Glasgow NHS Hospitals
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurology Clinical Military Medical Academy, Crnotravska 17
City
Belgrade
ZIP/Postal Code
11 000
Country
Serbia
Facility Name
Institute of Neurology Clinical Center Serbia Dr Subotica 6
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
University Hospital, Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Department of Neurology, Southern General Hospital
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
The Walton Centre
City
Liverpool
ZIP/Postal Code
L9 7LJ
Country
United Kingdom
Facility Name
Llandudno Hospital
City
Llandudno
ZIP/Postal Code
LL30 1LB
Country
United Kingdom
Facility Name
Newark Hospital
City
Newark
ZIP/Postal Code
NG24 4DE
Country
United Kingdom
Facility Name
Neurology Dept, Radcliffe Infirmary
City
Oxford
ZIP/Postal Code
OX2 6HE
Country
United Kingdom
Facility Name
Essex Neurosciences, UnitOld Church Hospital, Essex
City
Romford Essex
ZIP/Postal Code
RM7 0BE
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease
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