<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/NCT01683292</url>
  </required_header>
  <id_info>
    <org_study_id>VR040/001</org_study_id>
    <nct_id>NCT01683292</nct_id>
  </id_info>
  <brief_title>Single-Centre Study of VR040(Inhaled Apomorphine) in Idiopathic Parkinson's Disease</brief_title>
  <official_title>An Ascending-Dose, Single-Centre Study Investigating the Safety, Tolerability, Efficacy, and Pharmacokinetics of VR040(Inhaled Apomorphine)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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this first study of inhaled apomorphine in Parkinson's disease patients, the primary&#xD;
      objective is to find the minimum efficacious dose of apomorphine that is useful in rescuing&#xD;
      patients during 'off' periods. Safety, tolerability and pharmacokinetics of inhaled&#xD;
      apomorphine will be assessed during the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2006</start_date>
  <completion_date type="Actual">May 2007</completion_date>
  <primary_completion_date type="Actual">June 2006</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 proportion of patients &quot;on&quot; at any time post-dosing.</measure>
    <time_frame>up to 80 minutes</time_frame>
    <description>Parkinson's motor severity assessed by a clinician, and disease state assessment by the patient, were performed at baseline during an 'off' state, and at specified times after test drug administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration that patients remain in an &quot;on&quot; state.</measure>
    <time_frame>until return to &quot;off&quot; up to 3 hours</time_frame>
    <description>Time from when patient switched &quot;on&quot; after inhalation of study product, until patient returned to &quot;off&quot; state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Inhaled VR040</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inhaled apomorphine, dry powder, VR040 at fine particle doses (FPD) of 0.2mg, 0.5mg and 0.8mg. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Inhaled dry powder. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled VR040</intervention_name>
    <arm_group_label>Inhaled VR040</arm_group_label>
    <other_name>Inhaled apomorphine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for VR040</intervention_name>
    <description>Placebo arm</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with established idiopathic PD (via fulfilment of Steps 1 and 2 of the UK&#xD;
             Brain Bank Criteria), of at least 3 years duration prior to study entry, who were on&#xD;
             specific and optimised anti-Parkinson medication (levodopa and/or dopamine agonists),&#xD;
             and with motor fluctuations.&#xD;
&#xD;
          2. Patients with a modified Hoehn and Yahr disease severity scoring of between 2 and 4 in&#xD;
             an &quot;on&quot; state.&#xD;
&#xD;
          3. Men or women aged over 30 years.&#xD;
&#xD;
          4. Patients with a signed and dated written valid consent obtained prior to&#xD;
             participation.&#xD;
&#xD;
          5. Female patients must have been of non-childbearing potential (ie, physiologically&#xD;
             incapable of becoming pregnant, including any female who was post-menopausal) or of&#xD;
             child-bearing potential with a negative pregnancy test (urine or serum) at screening.&#xD;
&#xD;
          6. Patients who experienced motor fluctuations with recognisable &quot;off&quot; periods in control&#xD;
             of motor symptoms, as assessed by the motor fluctuation questionnaire (patients were&#xD;
             to have reported at least 1 &quot;Yes&quot; response to the questions in the motor fluctuation&#xD;
             questionnaire).&#xD;
&#xD;
          7. Patient willing and able to comply with study procedures.-&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who had participated in a trial with an investigational product within 3&#xD;
             months prior to randomisation at Visit 2.&#xD;
&#xD;
          2. Patients with serious uncontrolled disease including serious psychological disorders&#xD;
             likely to interfere with the study and/or likely to cause death within 6 months of the&#xD;
             study completion.&#xD;
&#xD;
          3. Patients with previous intolerance to apomorphine.&#xD;
&#xD;
          4. Patients with a previous significant complication from oral dopamine agonist therapy&#xD;
             including hospitalisation following dopamine agonist introduction and/or the&#xD;
             development of hallucinations or other adverse neuropsychiatric features following&#xD;
             introduction of sc apomorphine.&#xD;
&#xD;
          5. Women lactating, pregnant, or of child-bearing potential not using a reliable&#xD;
             contraceptive method.&#xD;
&#xD;
          6. Patients with known HIV or active chronic hepatitis B or C infection.&#xD;
&#xD;
          7. Patients with any clinically significant abnormality following review of screening&#xD;
             laboratory data and full physical examination.&#xD;
&#xD;
          8. Patients who, in the Investigator's opinion, were unsuitable for the study for any&#xD;
             reason.&#xD;
&#xD;
          9. Patients with clinically significant blood test abnormalities and previous medical&#xD;
             history/intercurrent illnesses that may have compromised the safety of the patient in&#xD;
             the study.&#xD;
&#xD;
         10. Patients with major ECG abnormalities (as judged by the Investigator).&#xD;
&#xD;
         11. Patients with a FEV1 &lt;65%.&#xD;
&#xD;
         12. Patients showing a postural decrease in systolic blood pressure (BP) of &gt; 20 mm Hg, or&#xD;
             showing significant clinical symptoms associated with orthostatic hypotension.&#xD;
&#xD;
         13. Patients with persistent elevation of BP, with average systolic readings of 160 mm Hg&#xD;
             or average diastolic readings of 100 mm Hg.&#xD;
&#xD;
         14. Patients taking anabolic steroids, traditional antipsychotics (unless low dose), and&#xD;
             antiemetics other than domperidone.&#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.&#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 schizophrenia, dementia, &quot;Parkinson&#xD;
             plus&quot; syndromes, or unstable systemic disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Southern General Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>September 7, 2012</last_update_submitted>
  <last_update_submitted_qc>September 7, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 11, 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>apomorphine</keyword>
  <keyword>inhaled</keyword>
  <keyword>motor fluctuations</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/NCT01683292
org study id: VR040/001
nct id: NCT01683292
lead sponsor: 
collaborator: 
has dmc: No
In this first study of inhaled apomorphine in Parkinson's disease patients, the primary
      objective is to find the minimum efficacious dose of apomorphine that is useful in rescuing
      patients during 'off' periods. Safety, tolerability and pharmacokinetics of inhaled
      apomorphine will be assessed during the study.
Objectives:
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The proportion of patients "on" at any time post-dosing.
time frame: up to 80 minutes
description: Parkinson's motor severity assessed by a clinician, and disease state assessment by the patient, were performed at baseline during an 'off' state, and at specified times after test drug administration.
measure: Duration that patients remain in an "on" state.
time frame: until return to "off" up to 3 hours
description: Time from when patient switched "on" after inhalation of study product, until patient returned to "off" state.
arm group label: Inhaled VR040
arm group type: Experimental
description: Inhaled apomorphine, dry powder, VR040 at fine particle doses (FPD) of 0.2mg, 0.5mg and 0.8mg. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.
arm group label: Placebo
arm group type: Placebo Comparator
description: Inhaled dry powder. A single dose, followed by a second dose at 12 minutes if efficacy end point was not attained.
intervention type: Drug
intervention name: Inhaled VR040
arm group label: Inhaled VR040
other name: Inhaled apomorphine
intervention type: Drug
intervention name: Placebo for VR040
description: Placebo arm
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
facility: 
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