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

September 25, 2012 updated by: Dr Donald Grosset, South Glasgow University Hospitals NHS Trust

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.

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Belgrade, Serbia, 11 000
        • Neurology Clinical Military Medical Academy, Crnotravska 17
      • Belgrade, Serbia, 11000
        • Institute of Neurology Clinical Center Serbia Dr Subotica 6
      • Cardiff, United Kingdom, CF14 4XW
        • University Hospital, Wales
      • Glasgow, United Kingdom, G51 4TF
        • Department of Neurology, Southern General Hospital
      • Liverpool, United Kingdom, L9 7LJ
        • The Walton Centre
      • Llandudno, United Kingdom, LL30 1LB
        • Llandudno Hospital
      • Newark, United Kingdom, NG24 4DE
        • Newark Hospital
      • Oxford, United Kingdom, OX2 6HE
        • Neurology Dept, Radcliffe Infirmary
      • Romford Essex, United Kingdom, RM7 0BE
        • Essex Neurosciences, UnitOld Church Hospital, Essex

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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.
Dry Powder inhaled apomorphine
Other Names:
  • 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.

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
The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
90 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to improvement from 'off' to 'on'
Time Frame: 90 minutes
Time to improvement from 'off' to 'on'.
90 minutes
The duration of 'on'
Time Frame: 90 minutes
The duration of 'on', the duration of time when the patient can function well.
90 minutes
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.
90 minutes

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
90minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Donald Grosset, MD, South Glasgow NHS Hospitals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

September 21, 2012

First Submitted That Met QC Criteria

September 25, 2012

First Posted (Estimate)

September 26, 2012

Study Record Updates

Last Update Posted (Estimate)

September 26, 2012

Last Update Submitted That Met QC Criteria

September 25, 2012

Last Verified

September 1, 2012

More Information

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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