<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01693081</url>
  </required_header>
  <id_info>
    <org_study_id>VR040/2/003</org_study_id>
    <nct_id>NCT01693081</nct_id>
  </id_info>
  <brief_title>Phase IIa Multicentre Study Investigating of VR040 in Parkinson's Disease</brief_title>
  <acronym>VR040/2/003</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>South Glasgow University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vectura Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>South Glasgow University Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      'Off periods' where people with Parkinson's disease are slow, stiff and unable to function&#xD;
      are disabling, and a treatment which can converts people to a &quot;on&quot;, good, able to function&#xD;
      state would be extremely useful. We assessed safety, tolerability and efficacy of inhaled dry&#xD;
      powder apomorphine (VR040) in a clinic-based study in this setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: 'Off' periods increase as Parkinson's disease progresses and the benefits of&#xD;
      standard therapy wane. Subcutaneous apomorphine rescues 'off' periods, but patient&#xD;
      self-injection and adverse cutaneous effects are sometimes problematic.&#xD;
&#xD;
      Methods: We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine&#xD;
      (VR040) in a clinic-based Phase II study. Of 48 patients recruited at 9 sites, 47 were&#xD;
      randomized 2:1 inhaled apomorphine:placebo. Respirable doses (drug predicted to reach the&#xD;
      lung) ascending through 1.5mg, 2.3mg, 3.0mg, and 4.0mg until efficacy was achieved, were&#xD;
      administered to patients in a practically defined 'off' state. The primary endpoint was the&#xD;
      response in unified Parkinson's disease rating scale Part 3 (UPDRS 3), at the highest dose&#xD;
      received by the patient. Secondary endpoints included time to 'on', the proportion of&#xD;
      patients converting from 'off' to 'on', and pharmacokinetics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2007</start_date>
  <completion_date type="Actual">July 2009</completion_date>
  <primary_completion_date type="Actual">July 2007</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The maximum UPDRS 3 improvement from pre-dose to post-dose</measure>
    <time_frame>90 minutes</time_frame>
    <description>The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to improvement from 'off' to 'on'</measure>
    <time_frame>90 minutes</time_frame>
    <description>Time to improvement from 'off' to 'on'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The duration of 'on'</measure>
    <time_frame>90 minutes</time_frame>
    <description>The duration of 'on', the duration of time when the patient can function well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients converting to 'on' any time after treatment administration.</measure>
    <time_frame>90 minutes</time_frame>
    <description>The proportion of patients converting to 'on' any time after treatment administration.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety variables</measure>
    <time_frame>90minutes</time_frame>
    <description>Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>VR040/Aspirair® inhaler</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VR040/Aspirair® inhaler</intervention_name>
    <description>Dry Powder inhaled apomorphine</description>
    <arm_group_label>VR040/Aspirair® inhaler</arm_group_label>
    <other_name>Inhaled apomorphine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female between 30 and 90 years old with idiopathic PD for at least 5 years.&#xD;
&#xD;
          2. Voluntary written informed consent provided.&#xD;
&#xD;
          3. Willing and able to comply with study procedures.&#xD;
&#xD;
          4. Fulfilled steps 1 and 2 of the UK Brain Bank Criteria.&#xD;
&#xD;
          5. Classified as Hoehn and Yahr Stage II to IV in &quot;on&quot; state.&#xD;
&#xD;
          6. Motor fluctuations with recognisable &quot;off&quot; periods in control of motor symptoms, as&#xD;
             assessed by the Motor Fluctuation Questionnaire.&#xD;
&#xD;
          7. Optimised oral therapy.&#xD;
&#xD;
          8. Dopaminergic responsiveness as defined by ≥ 30% improvement(reduction) in UPDRS III&#xD;
             score compared with pre-dose value.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participated in a trial with an investigational product within prior 3 months.&#xD;
&#xD;
          2. Serious uncontrolled disease including serious psychological disorders.&#xD;
&#xD;
          3. Previous intolerance to apomorphine.&#xD;
&#xD;
          4. Previous significant complication from oral dopamine agonist therapy&#xD;
&#xD;
          5. Women lactating, pregnant or of child-bearing potential not using a reliable&#xD;
             contraceptive method (eg, barrier, intrauterine device, abstinence).&#xD;
&#xD;
          6. Known HIV or active chronic hepatitis B or C infection.&#xD;
&#xD;
          7. Any clinically significant abnormality following review of screening observations&#xD;
&#xD;
          8. Patients who, in the Investigator's opinion, were unsuitable for the study for any&#xD;
             reason.&#xD;
&#xD;
          9. Major ECG abnormalities.&#xD;
&#xD;
         10. Patients with a FEV1 ≤ 65% predicted.&#xD;
&#xD;
         11. Patients showing a postural decrease in systolic blood pressure (BP) of ≥20 mm Hg or&#xD;
             showing significant clinical symptoms associated with orthostatic hypotension.&#xD;
&#xD;
         12. Patients with persistent arterial hypotension, with average systolic readings of ≤110&#xD;
             mm Hg.&#xD;
&#xD;
         13. Patients with persistent elevation of BP, with average systolic readings of ≥160 mm&#xD;
             Hg.&#xD;
&#xD;
             or average diastolic readings of ≥100 mm Hg.&#xD;
&#xD;
         14. Patients taking apomorphine at any time during these study visits, anabolic&#xD;
             steroids,traditional antipsychotics (unless low dose) and vasodilators other than for&#xD;
             the treatment of hypertension. The following atypical antipsychotics were permitted:&#xD;
             Quetiapine (up to and including 50 mg per day), risperidone (up to and including 1 mg&#xD;
             per day) and olanzapine (up to and including 2.5 mg per day).&#xD;
&#xD;
         15. Patients taking agents of the 5HT3 antagonist class including ondansetron,&#xD;
             granisetron,dolasetron, palonosetron and alosetron.&#xD;
&#xD;
         16. Patients with existing cancer and those in remission for less than 5 years.&#xD;
&#xD;
         17. Patients with evidence (as ascertained from examination, tests or history) to indicate&#xD;
             cardiovascular, gastrointestinal tract, liver, kidney, central nervous system,&#xD;
             pulmonary system or bone marrow disorders that in the Investigator's opinion&#xD;
             compromised patient safety.&#xD;
&#xD;
         18. Patients who were known non-responders to apomorphine treatment for &quot;off&quot; episodes(eg,&#xD;
             in previous challenge tests or trials).&#xD;
&#xD;
         19. Patients with a history of drug or alcohol abuse in the 12 months prior to entry.&#xD;
&#xD;
         20. Patients with a history of clinically significant allergies to VR040 formulation&#xD;
             constituents (including lactose and opioids) and domperidone.&#xD;
&#xD;
         21. Patients with signs or symptoms suggestive of psychosis, dementia, &quot;Parkinson-plus&quot;&#xD;
             syndromes or unstable systemic disease.&#xD;
&#xD;
         22. Patients with history of stroke, seizure or other neurological conditions.&#xD;
&#xD;
         23. Patients with dyskinesia rated 4 in Item 32 of UPDRS IV assessment at&#xD;
             Screening(dyskinesia present ≥76% of a waking day).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donald Grosset, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>South Glasgow NHS Hospitals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neurology Clinical Military Medical Academy, Crnotravska 17</name>
      <address>
        <city>Belgrade</city>
        <zip>11 000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Neurology Clinical Center Serbia Dr Subotica 6</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital, Wales</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Neurology, Southern General Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Walton Centre</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Llandudno Hospital</name>
      <address>
        <city>Llandudno</city>
        <zip>LL30 1LB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Hospital</name>
      <address>
        <city>Newark</city>
        <zip>NG24 4DE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Dept, Radcliffe Infirmary</name>
      <address>
        <city>Oxford</city>
        <zip>OX2 6HE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Essex Neurosciences, UnitOld Church Hospital, Essex</name>
      <address>
        <city>Romford Essex</city>
        <zip>RM7 0BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>September 25, 2012</last_update_submitted>
  <last_update_submitted_qc>September 25, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 26, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>South Glasgow University Hospitals NHS Trust</investigator_affiliation>
    <investigator_full_name>Dr Donald Grosset</investigator_full_name>
    <investigator_title>Consultant Neurologist</investigator_title>
  </responsible_party>
  <keyword>Parkinson's disease</keyword>
  <keyword>inhaled apomorphine</keyword>
  <keyword>convert &quot;off&quot; to &quot;on&quot;</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apomorphine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01693081
org study id: VR040/2/003
nct id: NCT01693081
lead sponsor: 
collaborator: 
has dmc: Yes
'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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The maximum UPDRS 3 improvement from pre-dose to post-dose
time frame: 90 minutes
description: The primary efficacy endpoint was the maximum UPDRS 3 improvement from pre-dose to post-dose at the highest dose used.
measure: Time to improvement from 'off' to 'on'
time frame: 90 minutes
description: Time to improvement from 'off' to 'on'.
measure: The duration of 'on'
time frame: 90 minutes
description: The duration of 'on', the duration of time when the patient can function well.
measure: The proportion of patients converting to 'on' any time after treatment administration.
time frame: 90 minutes
description: The proportion of patients converting to 'on' any time after treatment administration.
measure: Safety variables
time frame: 90minutes
description: Safety variables were: the pre- to post-dose change in vital signs, 12-lead ECG and continuous 12-lead Holter ECG, and lung function.
arm group label: VR040/Aspirair® inhaler
arm group type: Active Comparator
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: VR040/Aspirair® inhaler
description: Dry Powder inhaled apomorphine
arm group label: VR040/Aspirair® inhaler
other name: Inhaled apomorphine
intervention type: Drug
intervention name: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 90 Years
healthy volunteers: No
last name: Donald Grosset, MD
role: Principal Investigator
affiliation: South Glasgow NHS Hospitals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Serbia
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: South Glasgow University Hospitals NHS Trust
investigator full name: Dr Donald Grosset
investigator title: Consultant Neurologist
mesh term: Parkinson Disease
mesh term: Apomorphine