Parkinson's DiseasePhase 2VR040/2/003NCT01693081
Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease
A Phase 2 study testing VR040/Aspirair® inhaler in people with Parkinson's Disease, run by South Glasgow University Hospitals NHS Trust at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 90 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- VR040/Aspirair® inhaler
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Mar 2007to Jul 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United Kingdom7 sites
University Hospital, Wales
Cardiff, CF14 4XW
Department of Neurology, Southern General Hospital
Glasgow, G51 4TF
The Walton Centre
Liverpool, L9 7LJ
Llandudno Hospital
Llandudno, LL30 1LB
Newark Hospital
Newark, NG24 4DE
Neurology Dept, Radcliffe Infirmary
Oxford, OX2 6HE
Essex Neurosciences, UnitOld Church Hospital, Essex
Romford Essex, RM7 0BE
Serbia2 sites
Neurology Clinical Military Medical Academy, Crnotravska 17
Belgrade, 11 000
Institute of Neurology Clinical Center Serbia Dr Subotica 6
Belgrade, 11000
About this study
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
'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.
Read the 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.
- Conditions
- Parkinson's Disease
- Being tested
- VR040/Aspirair® inhaler, placebo
- Keywords
- Parkinson's disease, inhaled apomorphine, convert "off" to "on"
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VR040/Aspirair® inhalerDrug
Also called Inhaled apomorphine
Dry Powder inhaled apomorphine
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| VR040/Aspirair® inhaler | Active comparator | 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. Receives: Drug: VR040/Aspirair® inhaler |
| Placebo | Placebo comparator | 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 minutes
Secondary outcomes (3)
Time to improvement from 'off' to 'on'
Time to improvement from 'off' to 'on'.
Measured: 90 minutes
The duration of 'on'
The duration of 'on', the duration of time when the patient can function well.
Measured: 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.
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2012 (estimated)
- Study startMar 2007
- Primary completionJul 2007
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- South Glasgow University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Vectura Limited
- Responsible party
- Principal investigator, Dr Donald Grosset, South Glasgow University Hospitals NHS Trust
- Investigators
- Donald Grosset, MD, Principal investigator, South Glasgow NHS Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01693081
- Sponsor's protocol ID
- VR040/2/003
- Acronym
- VR040/2/003
- Status last verified
- Sep 2012
- First submitted
- 21 Sep 2012
- Last updated
- 26 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01693081
- Acronym / sponsor ID
- VR040/2/003 / VR040/2/003
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, inhaled apomorphine, convert "off" to "on"
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- South Glasgow University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Vectura Limited
- Study start
- Mar 2007
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 26 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
'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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VR040/Aspirair® inhaler | Active comparator | Drug: VR040/Aspirair® inhalerVR040 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 | Placebo comparator | Drug: placeboPlacebo 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. |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (24 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VR040/Aspirair® inhalerAlso: Inhaled apomorphineDry Powder inhaled apomorphine | Drug | VR040/Aspirair® inhaler |
| placebo | Drug | Placebo |
Primary outcome
The maximum UPDRS 3 improvement from pre-dose to post-dose
Time frame: 90 minutes
The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
3 secondary outcomes
Time to improvement from 'off' to 'on'
Time frame: 90 minutes
The duration of 'on'
Time frame: 90 minutes
The proportion of patients converting to 'on' any time after treatment administration.
Time frame: 90 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald Grosset, MD principal investigator
South Glasgow NHS Hospitals
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VR040/Aspirair® inhaler in people with Parkinson's Disease, run by South Glasgow University Hospitals NHS Trust at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The maximum UPDRS 3 improvement from pre-dose to post-dose (time frame: 90 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2012.