<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/NCT03777956</url>
  </required_header>
  <id_info>
    <org_study_id>LACOSAMIDE-2018</org_study_id>
    <secondary_id>2018-003110-40</secondary_id>
    <nct_id>NCT03777956</nct_id>
  </id_info>
  <brief_title>The Effect of Lacosamide in Peripheral Neuropathic Pain</brief_title>
  <official_title>The Effect of Lacosamide in Peripheral Neuropathic Pain: a Randomized, Double-blind, Placebo Controlled, Phenotype-stratified Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danish Pain Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Danish Pain Research Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to compare the change in pain intensity during treatment&#xD;
      with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with&#xD;
      and without the irritable nociceptor phenotype.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main purpose of this study is to compare the change in pain intensity during treatment&#xD;
      with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with&#xD;
      and without the irritable nociceptor phenotype. As this is a mechanistic study, the main&#xD;
      purpose is to compare the change in pain intensity in patients who receive an expected&#xD;
      sufficiently effective dose of lacosamide. As supportive evidence for a drug-specific&#xD;
      predictive biomarker, the purpose is also to compare the change in pain intensity during&#xD;
      lacosamide vs. placebo for the two phenotypes.&#xD;
&#xD;
      We hypothesize that the sodium-channel blocker lacosamide will be more effective in patients&#xD;
      with the irritable nociceptor than those without the non-irritable nociceptor phenotype, and&#xD;
      that lacosamide is more effective than placebo in patients with the irritable nociceptor&#xD;
      phenotype.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID 19 and recruitment problems&#xD;
  </why_stopped>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Actual">June 3, 2022</completion_date>
  <primary_completion_date type="Actual">June 3, 2022</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>Pain intensity</measure>
    <time_frame>12 weeks</time_frame>
    <description>The difference in the mean value of the patient's daily ratings of average pain intensity in the baseline week and the last week during treatment as experienced during the past 24 hours rated on a 0-10 point numeric rating scale (NRS; 0 = no pain, 10 = worst possible pain).&#xD;
The primary objective is to compare the change in pain intensity from baseline to last week of lacosamide treatment in patients with and without the irritable nociceptor phenotype in the PP population.&#xD;
The supportive objective is to compare the effect of lacosamide vs. placebo in the two phenotype groups in the PP population. Although we do not expect a phenotype difference in the response to placebo, a comparison of the effect of lacosamide vs. placebo is needed to justify that the phenotype is a predictive biomarker for the effect of lacosamide.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain relief</measure>
    <time_frame>12 weeks</time_frame>
    <description>(complete, good, moderate, mild, none, worse pain) . Measured at last visit/end of treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of escape medicine (paracetamol) during treatment period.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of paracetamol tablets during the 12 weeks treatment period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Neuropathic Pain</condition>
  <condition>Neuropathy;Peripheral</condition>
  <condition>Neuropathy, Painful</condition>
  <condition>Neuropathy, Diabetic</condition>
  <condition>Neuropathy</condition>
  <arm_group>
    <arm_group_label>Lacosamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lacosamide (50 mg) are given as capsules and taken orally twice a day, up to 200 mg b.i.d.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo are given as capsules, same as lacosamide, and taken orally twice a day, without active ingredient.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lacosamide</intervention_name>
    <description>Lacosamide (50 mg) and identical placebo are given as capsules and taken orally twice a day, up to 200 mg b.i.d.</description>
    <arm_group_label>Lacosamide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Identical placebo are given as capsules and taken orally twice a day.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years.&#xD;
&#xD;
          2. Probable or definite peripheral neuropathic pain for at least 3 months (Finnerup et&#xD;
             al. 2016)&#xD;
&#xD;
          3. Average pain intensity of at least 4 and not above 9 on a 0-10 NRS during the 7-day&#xD;
             baseline week (Dworkin et al. 2012).&#xD;
&#xD;
          4. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other causes of pain in the same area, or other concomitant pain that cannot be&#xD;
             distinguished from the neuropathic pain&#xD;
&#xD;
          2. Patient who cannot cooperate or are unable to complete the project and patients who do&#xD;
             not speak Danish.&#xD;
&#xD;
          3. Known and current cardiac conduction disturbance (2⁰ or 3⁰ atrioventricular (AV)&#xD;
             block, prolonged QTc interval &gt; 450 ms, heart rate &lt;50 or &gt;110 bpm, a QRS interval&#xD;
             &gt;120ms (ECG required)), significant cardiac, renal or liver disease or other severe&#xD;
             illness. In patients treated with pregabalin also PQ interval &gt; 0,2s and cardiac&#xD;
             disease. Sitting diastolic blood pressure below 50 mmHg or above 105 mmHg.&#xD;
&#xD;
          4. Major depressive episode within 6 months, recurrent depressive disorder or other&#xD;
             significant psychiatric disease, alcohol, illicit drug or drug abuse.&#xD;
&#xD;
          5. Pregnancy or lactation&#xD;
&#xD;
          6. Woman of childbearing potential, unless they use and acceptable effective&#xD;
             contraception measure as defined in the Clinical Trials Facilitation Group (CTFG)&#xD;
             during the study and at least 2 weeks after, or if their male partner is vasectomized&#xD;
             and their sole partners. Negative pregnancy test is required.&#xD;
&#xD;
          7. Known allergy to lacosamide or excipients.&#xD;
&#xD;
          8. Concomitant pain treatment with tricyclic antidepressants, topical analgesics&#xD;
             (lidocaine, capsaicin), lamotrigine, oxcarbazepine, cannabinoids or strong opioids&#xD;
             that cannot be discontinued. Other treatment for neuropathic pain are allowed in a&#xD;
             stable dose (from 14 days before randomization to completion of the trial), if they&#xD;
             cannot be tapered off completely.&#xD;
&#xD;
          9. Concomitant treatment with products known to be associated with PQ (PR) prolongation&#xD;
             other than pregabalin.&#xD;
&#xD;
         10. Patients inappropriate for placebo&#xD;
&#xD;
         11. Planned surgery&#xD;
&#xD;
         12. Use of sodium channel blockers within at least five half-lives and investigational&#xD;
             drugs within 30 days.&#xD;
&#xD;
         13. Patients on controlled sodium diet, unless the amount of sodium in the capsules is&#xD;
             acceptable for their diet.&#xD;
&#xD;
         14. The score &quot;yes&quot; on item 4 or item 5 of the Suicidal Ideation section of the Columbia&#xD;
             Suicide Severity Rating Scale (C-SSRS), if the ideation occurred in the past 6 months,&#xD;
             or &quot;yes on any item of the Suicidal Behaviour section, except for the &quot;Non-suicidal&#xD;
             Self Injurious Behaviour&quot; if this behaviour occurred in the past 2 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nanna B Finnerup, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Danish Pain Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Danish Pain Research Center, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.</citation>
    <PMID>27115670</PMID>
  </reference>
  <reference>
    <citation>Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice ASC, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain. 2012 Jun;153(6):1148-1158. doi: 10.1016/j.pain.2012.03.003. Epub 2012 Apr 9.</citation>
    <PMID>22494920</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Diabetic Neuropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lacosamide</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/NCT03777956
org study id: LACOSAMIDE-2018
secondary id: 2018-003110-40
nct id: NCT03777956
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main purpose of this study is to compare the change in pain intensity during treatment
      with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with
      and without the irritable nociceptor phenotype.
The main purpose of this study is to compare the change in pain intensity during treatment
      with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with
      and without the irritable nociceptor phenotype. As this is a mechanistic study, the main
      purpose is to compare the change in pain intensity in patients who receive an expected
      sufficiently effective dose of lacosamide. As supportive evidence for a drug-specific
      predictive biomarker, the purpose is also to compare the change in pain intensity during
      lacosamide vs. placebo for the two phenotypes.

      We hypothesize that the sodium-channel blocker lacosamide will be more effective in patients
      with the irritable nociceptor than those without the non-irritable nociceptor phenotype, and
      that lacosamide is more effective than placebo in patients with the irritable nociceptor
      phenotype.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain intensity
time frame: 12 weeks
description: The difference in the mean value of the patient's daily ratings of average pain intensity in the baseline week and the last week during treatment as experienced during the past 24 hours rated on a 0-10 point numeric rating scale (NRS; 0 = no pain, 10 = worst possible pain).
The primary objective is to compare the change in pain intensity from baseline to last week of lacosamide treatment in patients with and without the irritable nociceptor phenotype in the PP population.
The supportive objective is to compare the effect of lacosamide vs. placebo in the two phenotype groups in the PP population. Although we do not expect a phenotype difference in the response to placebo, a comparison of the effect of lacosamide vs. placebo is needed to justify that the phenotype is a predictive biomarker for the effect of lacosamide.
measure: Pain relief
time frame: 12 weeks
description: (complete, good, moderate, mild, none, worse pain) . Measured at last visit/end of treatment period.
measure: Use of escape medicine (paracetamol) during treatment period.
time frame: 12 weeks
description: Number of paracetamol tablets during the 12 weeks treatment period.
arm group label: Lacosamide
arm group type: Active Comparator
description: Lacosamide (50 mg) are given as capsules and taken orally twice a day, up to 200 mg b.i.d.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo are given as capsules, same as lacosamide, and taken orally twice a day, without active ingredient.
intervention type: Drug
intervention name: Lacosamide
description: Lacosamide (50 mg) and identical placebo are given as capsules and taken orally twice a day, up to 200 mg b.i.d.
arm group label: Lacosamide
intervention type: Drug
intervention name: Placebo
description: Identical placebo are given as capsules and taken orally twice a day.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nanna B Finnerup, Professor
role: Study Director
affiliation: Danish Pain Research Center
facility: 
country: Denmark
citation: Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.
PMID: 27115670
citation: Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice ASC, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain. 2012 Jun;153(6):1148-1158. doi: 10.1016/j.pain.2012.03.003. Epub 2012 Apr 9.
PMID: 22494920
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Neuralgia
mesh term: Diabetic Neuropathies
mesh term: Lacosamide