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

This study has been completed.
Sponsor:
Collaborator:
Vectura Limited
Information provided by (Responsible Party):
Dr Donald Grosset, South Glasgow University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01693081
First received: September 21, 2012
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

'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 Intervention Phase
Parkinson's Disease
Drug: VR040/Aspirair® inhaler
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by South Glasgow University Hospitals NHS Trust:

Primary Outcome Measures:
  • The maximum UPDRS 3 improvement from pre-dose to post-dose [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.


Secondary Outcome Measures:
  • Time to improvement from 'off' to 'on' [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    Time to improvement from 'off' to 'on'.

  • The duration of 'on' [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    The duration of 'on', the duration of time when the patient can function well.

  • The proportion of patients converting to 'on' any time after treatment administration. [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    The proportion of patients converting to 'on' any time after treatment administration.


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


Enrollment: 47
Study Start Date: March 2007
Study Completion Date: July 2009
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01693081

Locations
Serbia
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
Investigators
Principal Investigator: Donald Grosset, MD South Glasgow NHS Hospitals
  More Information

No publications provided

Responsible Party: Dr Donald Grosset, Consultant Neurologist, South Glasgow University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01693081     History of Changes
Other Study ID Numbers: VR040/2/003
Study First Received: September 21, 2012
Last Updated: September 25, 2012
Health Authority: United Kingdom: National Health Service

Keywords provided by South Glasgow University Hospitals NHS Trust:
Parkinson's disease
inhaled apomorphine
convert "off" to "on"

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Apomorphine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014