Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease

NCT ID: NCT01693081

Last Updated: 2012-09-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2009-07-31

Brief Summary

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'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

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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

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Parkinson's Disease

Keywords

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Parkinson's disease inhaled apomorphine convert "off" to "on"

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

VR040/Aspirair® inhaler

Intervention Type DRUG

Dry Powder inhaled apomorphine

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Interventions

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VR040/Aspirair® inhaler

Dry Powder inhaled apomorphine

Intervention Type DRUG

placebo

Intervention Type DRUG

Other Intervention Names

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Inhaled apomorphine

Eligibility Criteria

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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).
Minimum Eligible Age

30 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vectura Limited

INDUSTRY

Sponsor Role collaborator

South Glasgow University Hospitals NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Dr Donald Grosset

Consultant Neurologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Donald Grosset, MD

Role: PRINCIPAL_INVESTIGATOR

South Glasgow NHS Hospitals

Locations

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Neurology Clinical Military Medical Academy, Crnotravska 17

Belgrade, , Serbia

Site Status

Institute of Neurology Clinical Center Serbia Dr Subotica 6

Belgrade, , Serbia

Site Status

University Hospital, Wales

Cardiff, , United Kingdom

Site Status

Department of Neurology, Southern General Hospital

Glasgow, , United Kingdom

Site Status

The Walton Centre

Liverpool, , United Kingdom

Site Status

Llandudno Hospital

Llandudno, , United Kingdom

Site Status

Newark Hospital

Newark, , United Kingdom

Site Status

Neurology Dept, Radcliffe Infirmary

Oxford, , United Kingdom

Site Status

Essex Neurosciences, UnitOld Church Hospital, Essex

Romford Essex, , United Kingdom

Site Status

Countries

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Serbia United Kingdom

Other Identifiers

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VR040/2/003

Identifier Type: -

Identifier Source: org_study_id