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Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease (VR040/2/003)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01693081
Recruitment Status : Completed
First Posted : September 26, 2012
Last Update Posted : September 26, 2012
Vectura Limited
Information provided by (Responsible Party):
Dr Donald Grosset, South Glasgow University Hospitals NHS Trust

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: VR040/Aspirair® inhaler Drug: placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : March 2007
Actual Primary Completion Date : July 2007
Actual Study Completion Date : July 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.
Drug: placebo

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Time to improvement from 'off' to 'on' [ Time Frame: 90 minutes ]
    Time to improvement from 'off' to 'on'.

  2. The duration of 'on' [ Time Frame: 90 minutes ]
    The duration of 'on', the duration of time when the patient can function well.

  3. The proportion of patients converting to 'on' any time after treatment administration. [ Time Frame: 90 minutes ]
    The proportion of patients converting to 'on' any time after treatment administration.

Other Outcome Measures:
  1. Safety variables [ Time Frame: 90minutes ]
    Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.

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Ages Eligible for Study:   30 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female between 30 and 90 years old with idiopathic PD for at least 5 years.
  2. Voluntary written informed consent provided.
  3. Willing and able to comply with study procedures.
  4. Fulfilled steps 1 and 2 of the UK Brain Bank Criteria.
  5. Classified as Hoehn and Yahr Stage II to IV in "on" state.
  6. Motor fluctuations with recognisable "off" periods in control of motor symptoms, as assessed by the Motor Fluctuation Questionnaire.
  7. Optimised oral therapy.
  8. Dopaminergic responsiveness as defined by ≥ 30% improvement(reduction) in UPDRS III score compared with pre-dose value.

Exclusion Criteria:

  1. Participated in a trial with an investigational product within prior 3 months.
  2. Serious uncontrolled disease including serious psychological disorders.
  3. Previous intolerance to apomorphine.
  4. Previous significant complication from oral dopamine agonist therapy
  5. Women lactating, pregnant or of child-bearing potential not using a reliable contraceptive method (eg, barrier, intrauterine device, abstinence).
  6. Known HIV or active chronic hepatitis B or C infection.
  7. Any clinically significant abnormality following review of screening observations
  8. Patients who, in the Investigator's opinion, were unsuitable for the study for any reason.
  9. Major ECG abnormalities.
  10. Patients with a FEV1 ≤ 65% predicted.
  11. Patients showing a postural decrease in systolic blood pressure (BP) of ≥20 mm Hg or showing significant clinical symptoms associated with orthostatic hypotension.
  12. Patients with persistent arterial hypotension, with average systolic readings of ≤110 mm Hg.
  13. Patients with persistent elevation of BP, with average systolic readings of ≥160 mm Hg.

    or average diastolic readings of ≥100 mm Hg.

  14. 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).
  15. Patients taking agents of the 5HT3 antagonist class including ondansetron, granisetron,dolasetron, palonosetron and alosetron.
  16. Patients with existing cancer and those in remission for less than 5 years.
  17. 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.
  18. Patients who were known non-responders to apomorphine treatment for "off" episodes(eg, in previous challenge tests or trials).
  19. Patients with a history of drug or alcohol abuse in the 12 months prior to entry.
  20. Patients with a history of clinically significant allergies to VR040 formulation constituents (including lactose and opioids) and domperidone.
  21. Patients with signs or symptoms suggestive of psychosis, dementia, "Parkinson-plus" syndromes or unstable systemic disease.
  22. Patients with history of stroke, seizure or other neurological conditions.
  23. Patients with dyskinesia rated 4 in Item 32 of UPDRS IV assessment at Screening(dyskinesia present ≥76% of a waking day).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01693081

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Neurology Clinical Military Medical Academy, Crnotravska 17
Belgrade, Serbia, 11 000
Institute of Neurology Clinical Center Serbia Dr Subotica 6
Belgrade, Serbia, 11000
United Kingdom
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 Hospital
Llandudno, United Kingdom, LL30 1LB
Newark Hospital
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
Sponsors and Collaborators
South Glasgow University Hospitals NHS Trust
Vectura Limited
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Principal Investigator: Donald Grosset, MD South Glasgow NHS Hospitals

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Responsible Party: Dr Donald Grosset, Consultant Neurologist, South Glasgow University Hospitals NHS Trust Identifier: NCT01693081    
Other Study ID Numbers: VR040/2/003
First Posted: September 26, 2012    Key Record Dates
Last Update Posted: September 26, 2012
Last Verified: September 2012
Keywords provided by Dr Donald Grosset, South Glasgow University Hospitals NHS Trust:
Parkinson's disease
inhaled apomorphine
convert "off" to "on"
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action