- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01693081
Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease (VR040/2/003)
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Belgrade, Serbia, 11 000
- Neurology Clinical Military Medical Academy, Crnotravska 17
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Belgrade, Serbia, 11000
- Institute of Neurology Clinical Center Serbia Dr Subotica 6
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Cardiff, United Kingdom, CF14 4XW
- University Hospital, Wales
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Glasgow, United Kingdom, G51 4TF
- Department of Neurology, Southern General Hospital
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Liverpool, United Kingdom, L9 7LJ
- The Walton Centre
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Llandudno, United Kingdom, LL30 1LB
- Llandudno Hospital
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Newark, United Kingdom, NG24 4DE
- Newark Hospital
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Oxford, United Kingdom, OX2 6HE
- Neurology Dept, Radcliffe Infirmary
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Romford Essex, United Kingdom, RM7 0BE
- Essex Neurosciences, UnitOld Church Hospital, Essex
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Dry Powder inhaled apomorphine
Other Names:
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The maximum UPDRS 3 improvement from pre-dose to post-dose
Time Frame: 90 minutes
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The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
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90 minutes
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to improvement from 'off' to 'on'
Time Frame: 90 minutes
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Time to improvement from 'off' to 'on'.
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90 minutes
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The duration of 'on'
Time Frame: 90 minutes
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The duration of 'on', the duration of time when the patient can function well.
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90 minutes
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The proportion of patients converting to 'on' any time after treatment administration.
Time Frame: 90 minutes
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The proportion of patients converting to 'on' any time after treatment administration.
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90 minutes
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety variables
Time Frame: 90minutes
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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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90minutes
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Donald Grosset, MD, South Glasgow NHS Hospitals
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Gastrointestinal Agents
- Dopamine Agonists
- Dopamine Agents
- Emetics
- Apomorphine
Other Study ID Numbers
- VR040/2/003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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