<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/NCT03773055</url>
  </required_header>
  <id_info>
    <org_study_id>NPC-06-4</org_study_id>
    <nct_id>NCT03773055</nct_id>
  </id_info>
  <brief_title>Phase II Clinical Trial of NPC-06 in Patients With Neuropathic Pain in Cancer</brief_title>
  <official_title>A Multicenter, Double-blind, Randomized, Placebo-controlled Parallel Group Trial to Investigate the Proof of Concept of NPC-06 in Patients With Neuropathic Pain in Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nobelpharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nobelpharma</source>
  <oversight_info>
    <has_dmc>No</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 purpose of this trial is to investigate the efficiency of pain relief and the safety of&#xD;
      NPC-06 for the neuropathic pain associated with cancer, in addition to explore the effective&#xD;
      concentration of NPC-06.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The eligible patients will be randomized into three groups, and will receive NPC-06 (high&#xD;
      dose), NPC-06 (low dose) or placebo once a day for 7 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of Numeric Rating Scale (NRS) score within 2 hours after administration</measure>
    <time_frame>Pre-administration, 30, 60, 90 and 120 minutes post-administration</time_frame>
    <description>Average change (slope) of NRS score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Other improvements of NRS score</measure>
    <time_frame>Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13</time_frame>
    <description>Change of NRS score, Change of NRS score of persistent pain, Change of maximum pain, at the time of evaluation compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to event</measure>
    <time_frame>2 hours after initial administration to Day 7</time_frame>
    <description>Time to event analysis of analgesic effect</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of Neuropathic Pain Symptom Inventory (NPSI) score</measure>
    <time_frame>Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13</time_frame>
    <description>Change of NPSI score compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue medication use</measure>
    <time_frame>Day 1 to Day 13</time_frame>
    <description>Number of times of rescue medication use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective concentration</measure>
    <time_frame>Day 0 to Day 13</time_frame>
    <description>Blood phenytoin concentration</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Neuropathic Pain in Cancer</condition>
  <arm_group>
    <arm_group_label>NPC-06 (High dosage)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>18 mg (iv) in Day 1 as an induction dosage and 9 mg (iv) in Day 2 - 7 as a maintenance dosage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NPC-06 (Low dosage)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 mg (iv) in Day 1 as an induction dosage and 6 mg (iv) in Day 2 - 7 as a maintenance dosage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline will be administered intravenously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NPC-06</intervention_name>
    <description>Patients will receive once a day for 7 days.</description>
    <arm_group_label>NPC-06 (High dosage)</arm_group_label>
    <arm_group_label>NPC-06 (Low dosage)</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 16 years old or greater at the time of informed consent&#xD;
&#xD;
          2. Both genders&#xD;
&#xD;
          3. Patients who can admit to hospital for all assessment duration from first&#xD;
             administration until the next day of final administration. (including the hospitalized&#xD;
             patient )&#xD;
&#xD;
          4. Patients who are diagnosed and informed as cancer (including sarcoma, lymphoma and&#xD;
             multiple myeloma)&#xD;
&#xD;
          5. Patients who are diagnosed as neuropathic pain by neurological examination and imaging&#xD;
             findings&#xD;
&#xD;
          6. Patients who NRS score of average persistent pain is higher than 4, even they were&#xD;
             treated with level 3 of WHO three-step analgesic ladder at the observation period.&#xD;
&#xD;
          7. Patients who NRS score at the time of first administration and NRS score of persistent&#xD;
             pain in the past 24 hours are higher than 4.&#xD;
&#xD;
          8. Patients who average number of daily rescue medication use during observation period&#xD;
             is less than 6.&#xD;
&#xD;
          9. Patients who are predicted to survive longer than 3 month.&#xD;
&#xD;
         10. Patients who ECOG Performance Status (PS) score is 0 to 3.&#xD;
&#xD;
         11. Patients who (or whose legally acceptable representative if the patient is underage)&#xD;
             provide a written consent at their own will with a full understanding after receiving&#xD;
             a sufficient explanation on participation in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who can not evaluate NRS by themselves.&#xD;
&#xD;
          2. Patients who have leukemia as a complication.&#xD;
&#xD;
          3. Patients who have a primary brain neoplasm or a metastatic brain neoplasm as a&#xD;
             complication.&#xD;
&#xD;
          4. Patients who have epilepsy, serious psychiatric or neurological disease ( i. e.&#xD;
             dementia, Parkinson disease or schizophrenic disorder) or consciousness disturbance as&#xD;
             a complication.&#xD;
&#xD;
          5. Patients who have primary trigeminal neuralgia, diabetic neuropathy, post herpetic&#xD;
             neuralgia or acute herpes zoster pain as a complication.&#xD;
&#xD;
          6. Patients who has other serious pain which affect the evaluation of neuropathic pain in&#xD;
             cancer.&#xD;
&#xD;
          7. Patients who have sinus bradycardia or serious disturbance of conduction system.&#xD;
&#xD;
          8. Patients who have history of hypersensitivity against hydantoin compound.&#xD;
&#xD;
          9. Patients who are administrated tadalafil (for pulmonary hypertension), rilpivirine,&#xD;
             asunaprevir, daclatasvir, vaniprevir, macitentan or sofosbuvir.&#xD;
&#xD;
         10. Patients who are administrated methadone.&#xD;
&#xD;
         11. Patients who have complications such as serious heart disease, hepatic function&#xD;
             disorder or renal function disorder which severity are considered by investigator as&#xD;
             grade 3 or more severe with reference to ''Concerning classification criteria for&#xD;
             seriousness of adverse drug reactions of medical agents'' (except cancer).&#xD;
&#xD;
         12. Patients who received surgical treatment or internal radiation therapy in past three&#xD;
             month before the first day of pre observation period.&#xD;
&#xD;
         13. Patients who are treated nerve block, radiation therapy, spinal cord stimulation or&#xD;
             surgical treatment for the part of neuropathic pain in past one month before the first&#xD;
             day of pre observation period.&#xD;
&#xD;
         14. Patients who change the usage or dosage of medication for cancer as primal disease in&#xD;
             the past two week before the first day of the pre observation period, or patients who&#xD;
             are predicted not to continue the treatment without change in the medication while&#xD;
             this clinical trial.&#xD;
&#xD;
         15. Patients who are administrating with fosphenytoin, phenytoin or ethotoin or have taken&#xD;
             these drugs as medication for neuropathic pain.&#xD;
&#xD;
         16. Patients who have participated in other clinical trial and have taken a trial drug in&#xD;
             past three month before the first day of pre observation period.&#xD;
&#xD;
         17. Female patients who are pregnant or lactating or who may be pregnancy in the period of&#xD;
             the clinical trial.&#xD;
&#xD;
         18. Patients who can not agree to prevent contraception appropriately following the&#xD;
             direction of the Investigator or the sub-investigator.&#xD;
&#xD;
         19. Any other patients who are considered by the investigator as unsuitable for&#xD;
             participation in the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Keio Hospital</name>
      <address>
        <city>Shinjuku-Ku</city>
        <state>Tokyo</state>
        <zip>160-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>November 12, 2020</last_update_submitted>
  <last_update_submitted_qc>November 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2020</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>Neuralgia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03773055
org study id: NPC-06-4
nct id: NCT03773055
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this trial is to investigate the efficiency of pain relief and the safety of
      NPC-06 for the neuropathic pain associated with cancer, in addition to explore the effective
      concentration of NPC-06.
The eligible patients will be randomized into three groups, and will receive NPC-06 (high
      dose), NPC-06 (low dose) or placebo once a day for 7 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Improvement of Numeric Rating Scale (NRS) score within 2 hours after administration
time frame: Pre-administration, 30, 60, 90 and 120 minutes post-administration
description: Average change (slope) of NRS score
measure: Other improvements of NRS score
time frame: Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13
description: Change of NRS score, Change of NRS score of persistent pain, Change of maximum pain, at the time of evaluation compared to baseline
measure: Time to event
time frame: 2 hours after initial administration to Day 7
description: Time to event analysis of analgesic effect
measure: Improvement of Neuropathic Pain Symptom Inventory (NPSI) score
time frame: Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13
description: Change of NPSI score compared to baseline
measure: Rescue medication use
time frame: Day 1 to Day 13
description: Number of times of rescue medication use
measure: Effective concentration
time frame: Day 0 to Day 13
description: Blood phenytoin concentration
arm group label: NPC-06 (High dosage)
arm group type: Active Comparator
description: 18 mg (iv) in Day 1 as an induction dosage and 9 mg (iv) in Day 2 - 7 as a maintenance dosage
arm group label: NPC-06 (Low dosage)
arm group type: Active Comparator
description: 15 mg (iv) in Day 1 as an induction dosage and 6 mg (iv) in Day 2 - 7 as a maintenance dosage
arm group label: Placebo
arm group type: Placebo Comparator
description: Saline will be administered intravenously
intervention type: Drug
intervention name: NPC-06
description: Patients will receive once a day for 7 days.
arm group label: NPC-06 (High dosage)
arm group label: NPC-06 (Low dosage)
arm group label: Placebo
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Neuralgia
sharing ipd: No