<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/NCT04429919</url>
  </required_header>
  <id_info>
    <org_study_id>AP-325.04</org_study_id>
    <nct_id>NCT04429919</nct_id>
  </id_info>
  <brief_title>AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain</brief_title>
  <official_title>A Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of AP-325 in Subjects With Peripheral Post-surgical Neuropathic Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Algiax Pharmaceuticals GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FGK Clinical Research GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Algiax Pharmaceuticals GmbH</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>
      This is a Phase IIa randomized, double-blind, placebo-controlled study. The study objective&#xD;
      is to investigate the efficacy and safety of repeat oral dosing of the investigational&#xD;
      medicinal product (IMP) AP-325 for the treatment of peripheral post-surgical neuropathic pain&#xD;
      (PPNP) after breast surgery (breast-conserving surgery, mastectomy, surgery to remove lymph&#xD;
      nodes), chest surgery (e.g. thoracotomy, video assisted thoracoscopy and sternotomy), hernia&#xD;
      repair of the abdominal wall (e.g. femoral hernia repairs, inguinal hernia repairs, umbilical&#xD;
      hernia repair or incisional hernia repair), abdominal surgery (e.g. cholecystectomy,&#xD;
      appendectomy but also see exclusion criterion 15), varicose vein surgery or gynecologic&#xD;
      surgery (e.g. hysterectomy, C-section).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase IIa randomized, double-blind, placebo controlled, parallel group study to&#xD;
      evaluate the efficacy (by changes in Pain Intensity Numerical Rating Scale [PI-NRS]) and&#xD;
      safety (by monitoring adverse events) of AP-325 in subjects with PPNP.&#xD;
&#xD;
      The clinical trial will be conducted in Germany, Spain and Czech Republic.&#xD;
&#xD;
      Eligible subjects will undergo a 2-week run-in period consisting of a washout-period of&#xD;
      prohibited medications in the 1st week and a baseline period in the 2nd week. If subjects&#xD;
      have at least 5 self-reported pain assessments in the baseline period (documented in a diary)&#xD;
      and meet the required pain criteria, they will be randomized to AP-325 or placebo in a 1:1&#xD;
      ratio.&#xD;
&#xD;
      Subjects will take the IMP (AP-325 or placebo) for 10 days (double-blind treatment period;&#xD;
      Days 1-10) and then be followed up for a further 26 days (drug-free period; Days 11-36). An&#xD;
      end of study visit will be performed on Day 36.&#xD;
&#xD;
      At least 96 subjects (48 for each treatment) need to be analyzed for the primary endpoint at&#xD;
      Day 10 to reach the power estimate (120 subjects should be screened for the study).&#xD;
&#xD;
      AP-325 100 mg (4 x 25 mg capsules) or Placebo (4 capsules) will be orally taken once daily in&#xD;
      the morning before meals for 10 consecutive days.&#xD;
&#xD;
      Pain will be assessed, and quality of life will be investigated using standardized and&#xD;
      validated questionnaires [Pain Intensity Numerical Rating Scale (PI-NRS), patient global&#xD;
      impression of change (PGIC), neuropathic pain symptom inventory (NPSI) questionnaire, daily&#xD;
      sleep interference scale (DSIS) score, hospital anxiety and depression scale (HADS)].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">April 2024</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>
    <intervention_model_description>placebo controlled, Phase IIa clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline to Day 10 in the 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS; ranges from &quot;no pain&quot; = 0 to &quot;the worst possible pain&quot; = 10; the lower the score, the better the outcome)</measure>
    <time_frame>Baseline to Day 10</time_frame>
    <description>The 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS) will be assessed to investigate the efficacy of repeat oral dosing of AP-325</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Longitudinal analysis of the 5-day average PI-NRS score (ranges from &quot;no pain&quot; = 0 to &quot;the worst possible pain&quot; = 10; the lower the score, the better the outcome) over time from Baseline until Day 35</measure>
    <time_frame>Baseline to Day 35</time_frame>
    <description>The 5-day average PI-NRS score will be assessed to investigate the long-lasting efficacy of repeat oral dosing of AP-325 on neuropathic pain over the entire study duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in the 5-day average PI-NRS score (change can be in the range of 0 to 10; the bigger the change towards lower PI-NRS scores, the better the outcome) (from Baseline to Day 5, 15, 20, 25, 30 and 35)</measure>
    <time_frame>Baseline to Day 5, 15, 20, 25, 30 and 35</time_frame>
    <description>The 5-day average PI-NRS score will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder rate: proportion of subjects who have a ≥30% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)</measure>
    <time_frame>Baseline to Day 5, 10, 15, 25 and 35</time_frame>
    <description>The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder rate: proportion of subjects who have a ≥50% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)</measure>
    <time_frame>Baseline to Day 5, 10, 15, 25 and 35</time_frame>
    <description>The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who &quot;much improved&quot; or &quot;very much improved&quot; relative to Baseline on the patient global impression of change (PGIC) on Days 3, 10, 15, and 36</measure>
    <time_frame>Days 3, 10, 15, and 36</time_frame>
    <description>The PGIC will be dichotomized into treatment success (i.e. scoring 'much improved' or 'very much improved').</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in the neuropathic pain evaluation using the neuropathic pain symptom inventory (NPSI; ranges from &quot;no pain&quot; = 0 to &quot;the worst possible pain&quot; = 120; the lower the score, the better) questionnaire on Days 3, 10, 15, and 36</measure>
    <time_frame>Baseline, Day 3, 10, 15 and 36</time_frame>
    <description>Neuropathic pain symptom inventory (NPSI) questionnaire to assess the neuropathic pain of the patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in the 5-day average daily sleep interference scale (DSIS; ranges from &quot;pain does not interfere with sleep&quot; = 0 to &quot;pain completely interferes with sleep&quot; = 10) score (from Baseline to Day 5, 10, 15, 25 and 35)</measure>
    <time_frame>Baseline to Day 5, 10, 15, 25 and 35</time_frame>
    <description>The 5-day average daily sleep interference scale (DSIS) score will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in the anxiety and depression assessment using the hospital anxiety and depression scale (HADS; subscales range from 0 to 21, with higher values indicating higher anxiety or depression; the lower the score) on Days 10 and 36</measure>
    <time_frame>Baseline, Day 10 and 36</time_frame>
    <description>The hospital anxiety and depression scale (HADS) to assess the anxiety and depression of the patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first use of rescue medication after randomization</measure>
    <time_frame>A priori specification not possible, between Day 1 until Day 36</time_frame>
    <description>The time to first use of rescue medication after randomization will be analyzed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total amount of rescue medication use (in mg per day) after randomization</measure>
    <time_frame>A priori specification not possible, between Day 1 until Day 36</time_frame>
    <description>The total amount of rescue medication (i.e. the total mg of rescue medication per day will be tabulated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects classified as treatment failure</measure>
    <time_frame>A priori specification not possible, between Day1 and Day 36</time_frame>
    <description>Proportion of subjects classified as treatment failure at least once after randomization will be tabulated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to classification as treatment failure after randomization</measure>
    <time_frame>A priori specification not possible, between Day1 and Day 36</time_frame>
    <description>Time to first classification as treatment failure after randomization will be analyzed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>A priori specification not possible, between Day1 and Day 36</time_frame>
    <description>All TEAEs occurring during the clinical trial will be registered, documented and evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal physical examinations</measure>
    <time_frame>Baseline, Day 3, 10, 15 and 36</time_frame>
    <description>Abnormal physical examination results will be evaluated and reported as AEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in vital signs: Systolic and diastolic blood pressure</measure>
    <time_frame>Baseline, Day 1, 3, 10, 15 and 36</time_frame>
    <description>Systolic and diastolic blood pressure will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in vital signs: Heart rate</measure>
    <time_frame>Baseline, Day 1, 3, 10, 15 and 36</time_frame>
    <description>Heart rate will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in vital signs: Respiratory rate</measure>
    <time_frame>Baseline, Day 1, 3, 10, 15 and 36</time_frame>
    <description>Respiratory rate will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in vital signs: Aural body temperature</measure>
    <time_frame>Baseline, Day 1, 3, 10, 15 and 36</time_frame>
    <description>Aural body temperature will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal laboratory test results</measure>
    <time_frame>Baseline, Day 3, 10, 15 and 36</time_frame>
    <description>Abnormal laboratory test results will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal ECG readings</measure>
    <time_frame>Baseline, Day 3, 10 and 36</time_frame>
    <description>Abnormal 12 lead ECG readings will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in body weight</measure>
    <time_frame>Baseline, Day 10 and 36</time_frame>
    <description>Body weight will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations of AP-325 at 1 hour post-dose on Days 1 and 10; pre-dose on Days 3 and 10; and on Day 36</measure>
    <time_frame>Days 1, 3, 10 and 36</time_frame>
    <description>Plasma concentrations of AP-325 will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation of Ctrough from Day 3 to Day 10</measure>
    <time_frame>Day 3 and 10</time_frame>
    <description>Plasma concentrations of AP-325 will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between Ctrough-ss (Day 10) and the change from Baseline to Day 10 in the 5-day average pain intensity score based on the PI-NRS</measure>
    <time_frame>Baseline to Day 10</time_frame>
    <description>AP-325 concentration-effect relationships will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between CYP2C9 genotype and the metabolism of AP-325 (optional)</measure>
    <time_frame>Day 3</time_frame>
    <description>The effect of CYP2C9 polymorphisms (determined by CYP2C9 genotyping) on the plasma concentration of AP-325 will be evaluated</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Peripheral Post-surgical Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>AP-325</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 mg capsule for oral use, 4 capsules (100 mg) once daily in the morning before meals</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 capsules once daily in the morning before meals</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AP-325</intervention_name>
    <description>During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.</description>
    <arm_group_label>AP-325</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects must be at least 18 years and not older than 80 years&#xD;
&#xD;
          2. Subjects with a diagnosis of chronic post-surgical neuropathic pain after breast&#xD;
             surgery (e.g. breast-conserving surgery, mastectomy, surgery to remove lymph nodes),&#xD;
             chest surgery (e.g. thoracotomy, video assisted thoracoscopy and sternotomy), hernia&#xD;
             repair of the abdominal wall (e.g. femoral hernia repairs, inguinal hernia repairs,&#xD;
             umbilical hernia repair or incisional hernia repair), abdominal surgery (e.g.&#xD;
             cholecystectomy, appendectomy but also see exclusion criterion 15), varicose vein&#xD;
             surgery or gynecologic surgery (e.g. hysterectomy, C-section)&#xD;
&#xD;
          3. The chronic post-surgical pain developed or increased in intensity after the surgical&#xD;
             procedure and persisted beyond the healing process, i.e. at least 3 months after the&#xD;
             initiating event, as defined according to the international association for the study&#xD;
             of pain (IASP) classification of chronic pain for ICD-11 (Schug et al., 2019)&#xD;
&#xD;
          4. Subjects must have 'probable' or 'definite' neuropathic pain as assessed by the&#xD;
             revised IASP special interest group on neuropathic pain (NeuPSIG) grading system&#xD;
             (Finnerup et al., 2016)&#xD;
&#xD;
          5. Subjects must be willing and able to discontinue and washout prohibited substances&#xD;
             including&#xD;
&#xD;
               -  pain medications (e.g. antidepressants, anticonvulsants/antiepileptics, selective&#xD;
                  serotonin and dual reuptake inhibitors, opioids, long-acting benzodiazepines,&#xD;
                  muscle relaxants, and topical analgesics), except the rescue medication, and&#xD;
&#xD;
               -  substances known to be inhibitors or inducers of CYP2C9 and inhibitors of CYP3A4&#xD;
                  for specific washout periods of at least 5 times the drug half-life Note:&#xD;
                  Subjects using prohibited substances for other indications than neuropathic pain,&#xD;
                  e.g. antiepileptics for the treatment of epilepsy, may not be included in the&#xD;
                  study, because a discontinuation of such medication is not medically justifiable.&#xD;
&#xD;
          6. Permitted concomitant medications must have been stable for at least 4 weeks prior to&#xD;
             Day -14 and any non-pharmacological therapies (e.g. physiotherapy, acupuncture and&#xD;
             transcutaneous electrical neural stimulation) must have been initiated at least 3&#xD;
             weeks prior to Screening&#xD;
&#xD;
          7. Female subjects must not be pregnant or breastfeeding and be&#xD;
&#xD;
               -  of non-childbearing potential or&#xD;
&#xD;
               -  if of childbearing potential, use a highly effective contraceptive method from&#xD;
                  start of the IMP intake until 30 days after the last IMP intake and have a&#xD;
                  negative pregnancy test at Screening (blood test)&#xD;
&#xD;
          8. Male subjects must agree, from start of the IMP intake until 3 months after the last&#xD;
             IMP intake, to refrain from donating sperm and use a male condom when having sexual&#xD;
             intercourse with a woman of childbearing potential at any time and advise her to use a&#xD;
             highly effective contraceptive method&#xD;
&#xD;
          9. Subjects must understand the nature of the study procedures and provide written&#xD;
             informed consent prior to any study-related procedures&#xD;
&#xD;
         10. Body weight ≥55 kg for men and ≥50 kg for women&#xD;
&#xD;
         11. Body mass index (BMI) &lt;40 kg/m²&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with neuropathic pain not a result of a surgical procedure as defined in&#xD;
             inclusion criterion 2&#xD;
&#xD;
          2. Subjects with any other coexisting pain that cannot be discriminated from&#xD;
             post-surgical neuropathic pain, in the opinion of the subject or clinician e.g., the&#xD;
             pain is at least partially due to pain in deeper structures such as internal organs,&#xD;
             joints, muscles or bones&#xD;
&#xD;
          3. Inability to participate in the study, in the opinion of the investigator, because of,&#xD;
             for example, severe brain damage, language barrier, dementia, or other clinically&#xD;
             significant or unstable conditions&#xD;
&#xD;
          4. Subjects using adjuvant chemotherapy or radiotherapy; adjuvant therapies must have&#xD;
             been finished at least 4 weeks prior to the run-in period (Day -14)&#xD;
&#xD;
          5. Creatinine clearance &lt;60 mL/min using the Cockcroft-Gault formula&#xD;
&#xD;
          6. White blood cell count &lt;2500/mm³; neutrophil count &lt;1500/mm³; platelet count &lt;100 x&#xD;
             103/mm³&#xD;
&#xD;
          7. Heart rate &lt;50 or &gt;100 beats per minute; systolic blood pressure &lt;100 or &gt;140 mmHg;&#xD;
             diastolic blood pressure &lt;50 or &gt;90 mmHg after 5 minutes rest in supine position&#xD;
&#xD;
          8. A history of multiple drug allergies&#xD;
&#xD;
          9. History or presence of alcohol or drug abuse&#xD;
&#xD;
         10. Subjects using strong opioids (e.g. a Morphine Equivalent Dose [MED] &gt;80 mg/day)&#xD;
&#xD;
         11. Positive test for drugs of abuse at Day -7&#xD;
&#xD;
         12. Evidence of depression and/or a score of ≥11 on the HADS depression subscale&#xD;
&#xD;
         13. Any clinically relevant psychiatric disease in the past 5 years which is likely to&#xD;
             interfere with the conduct of the study&#xD;
&#xD;
         14. History of any clinically relevant liver disease within the last 6 months, or&#xD;
             episodic/chronic migraine, or kidney dysfunction or disease&#xD;
&#xD;
         15. Clinically significant gastrointestinal conditions, likely interfering with the study&#xD;
             medication, study procedures or the outcome of the study&#xD;
&#xD;
         16. Positive test for human immunodeficiency virus (HIV)&#xD;
&#xD;
         17. Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody&#xD;
             (HBcAb), hepatitis C antibody and/or HIV1/HIV2 antibody at Screening&#xD;
&#xD;
         18. Participation of subject in an interventional clinical study within 1 month or, if&#xD;
             applicable, 5 half-lives of the IMP, whatever is longer, before Screening or during&#xD;
             participation in this study&#xD;
&#xD;
         19. Subjects who were previously enrolled in this clinical study and have taken study&#xD;
             medication or terminated due to poor compliance&#xD;
&#xD;
         20. Known hypersensitivity to the active substance or any of the excipients of the IMP or&#xD;
             the rescue medication&#xD;
&#xD;
         21. Subjects dependent (as an employee or relative) on the sponsor or investigator&#xD;
&#xD;
         22. Subjects committed to an institution by virtue of an order issued either by the&#xD;
             judicial or the administrative authorities&#xD;
&#xD;
         23. Legal incapacity or limited legal capacity&#xD;
&#xD;
        Randomization criteria&#xD;
&#xD;
          1. At least 5 daily pain assessments in the baseline week prior to randomization, with a&#xD;
             mean score on the PI-NRS ≥4 and ≤9. Differences between the baseline daily pain scores&#xD;
             on the PI-NRS must be ≤50%.&#xD;
&#xD;
          2. For female subjects of childbearing potential: negative pregnancy test in urine on Day&#xD;
             1.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heike Rittner, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Würzburg, Interdisziplinäre Schmerzmedizin, Germany</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Guido Koopmans</last_name>
    <phone>+49 211 617851</phone>
    <phone_ext>0</phone_ext>
    <email>info@algiax.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Neurology and Physiotherapy Outpatient Clinic Skopalíkova</name>
      <address>
        <city>Brno</city>
        <zip>61500</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eduard Minks, MUDr., Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>NEUROHK, s.r.o.</name>
      <address>
        <city>Choceň</city>
        <zip>56501</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin Vališ, doc., Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>NeuropsychiatrieHK, s.r.o.</name>
      <address>
        <city>Hradec Králové</city>
        <zip>50341</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Neuros, s.r.o.</name>
      <address>
        <city>Plzen</city>
        <zip>301 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hana Rosenbergová, MUDr.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>DADO Medical s.r.o.</name>
      <address>
        <city>Praha 2</city>
        <zip>12000</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Fakultní nemocnice Královské Vinohrady, Klinika anestezologie a resuscitace</name>
      <address>
        <city>Praha</city>
        <zip>100 34</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Praglandia, s.r.o.</name>
      <address>
        <city>Praha</city>
        <zip>150 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Ungerová, MUDr.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>MP-neuro s.r.o., Poliklinika Modrý pavilon</name>
      <address>
        <city>Slezská Ostrava</city>
        <zip>71000</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Danuše Roubcová, MUDr.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ALGOMED s.r.o. - Centrum léčby bolesti</name>
      <address>
        <city>České Budějovice</city>
        <zip>370 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nataša Popperová, MUDr.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>emovis GmbH, Dedicated Study Site</name>
      <address>
        <city>Berlin</city>
        <zip>10629</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Vivantes Klinikum Neukölln, Klinik für Thoraxchirurgie</name>
      <address>
        <city>Berlin</city>
        <zip>12351</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, (Ruhr-Universität Bochum) Neurologische Klinik und Poliklinik</name>
      <address>
        <city>Bochum</city>
        <zip>44789</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Florence-Nightingale-Krankenhaus der Kaiserswerther Diakonie, Klinik für Thoraxchirurgie</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40489</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Kliniken der Stadt Köln gGmbH, Krankenhaus Köln-Holweide, Brustzentrum</name>
      <address>
        <city>Köln</city>
        <zip>51067</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Kliniken der Stadt Köln gGmbH, Krankenhaus Köln-Merheim, Lungenklinik am Zentrum für Thoraxchirurgie, Pneumologie/ Onkologie, Schlaf- und Beatmungsmedizin, Klinikum der Universität Witten/Herdecke</name>
      <address>
        <city>Köln</city>
        <zip>51109</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>medamed GmbH, Sudienambulanz Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. med. J. Springub und W. Schwarz, Studienzentrum Nordwest</name>
      <address>
        <city>Westerstede</city>
        <zip>26655</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie, Zentrum für Interdisziplinäre Schmerzmedizin</name>
      <address>
        <city>Würzburg</city>
        <zip>97078</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>HOSPITAL DEL MAR.#Cod. CNH: 080057#</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonio Montes Pérez, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARIO PUERTA DEL MAR#Cod. CNH: 110012#</name>
      <address>
        <city>Cadiz</city>
        <zip>11009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luis Miguel Torres, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARI DE BELLVITGE#Cod. CNH: 080752#</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrés Ancor Serrano Afonso, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARIO 12 DE OCTUBRE#Cod. CNH: 280035#</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudia Sarrais Polo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARIO LA PAZ#Cod. CNH: 280014#</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Javier De Andrés Ares, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARIO LA MORALEJA#Cod. CNH: 281179#</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alejandro Orts Castro, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CLINICA UNIVERSIDAD DE NAVARRA#Cod. CNH: 310060#</name>
      <address>
        <city>Pamplona/Iruña</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas Varela, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID#Cod. CNH: 281203#</name>
      <address>
        <city>Pozuelo de Alarcón</city>
        <zip>28223</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva M Monzón Rubio, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>HOSPITAL CLINICO UNIVERSITARIO DE VALENCIA#Cod. CNH: 460044#</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juan C Tornero Tornero, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>February 23, 2023</last_update_submitted>
  <last_update_submitted_qc>February 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AP-325</keyword>
  <keyword>Phase IIa</keyword>
  <keyword>PPNP</keyword>
  <keyword>post-surgical neuropathic pain</keyword>
  <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/NCT04429919
org study id: AP-325.04
nct id: NCT04429919
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a Phase IIa randomized, double-blind, placebo-controlled study. The study objective
      is to investigate the efficacy and safety of repeat oral dosing of the investigational
      medicinal product (IMP) AP-325 for the treatment of peripheral post-surgical neuropathic pain
      (PPNP) after breast surgery (breast-conserving surgery, mastectomy, surgery to remove lymph
      nodes), chest surgery (e.g. thoracotomy, video assisted thoracoscopy and sternotomy), hernia
      repair of the abdominal wall (e.g. femoral hernia repairs, inguinal hernia repairs, umbilical
      hernia repair or incisional hernia repair), abdominal surgery (e.g. cholecystectomy,
      appendectomy but also see exclusion criterion 15), varicose vein surgery or gynecologic
      surgery (e.g. hysterectomy, C-section).
This is a Phase IIa randomized, double-blind, placebo controlled, parallel group study to
      evaluate the efficacy (by changes in Pain Intensity Numerical Rating Scale [PI-NRS]) and
      safety (by monitoring adverse events) of AP-325 in subjects with PPNP.

      The clinical trial will be conducted in Germany, Spain and Czech Republic.

      Eligible subjects will undergo a 2-week run-in period consisting of a washout-period of
      prohibited medications in the 1st week and a baseline period in the 2nd week. If subjects
      have at least 5 self-reported pain assessments in the baseline period (documented in a diary)
      and meet the required pain criteria, they will be randomized to AP-325 or placebo in a 1:1
      ratio.

      Subjects will take the IMP (AP-325 or placebo) for 10 days (double-blind treatment period;
      Days 1-10) and then be followed up for a further 26 days (drug-free period; Days 11-36). An
      end of study visit will be performed on Day 36.

      At least 96 subjects (48 for each treatment) need to be analyzed for the primary endpoint at
      Day 10 to reach the power estimate (120 subjects should be screened for the study).

      AP-325 100 mg (4 x 25 mg capsules) or Placebo (4 capsules) will be orally taken once daily in
      the morning before meals for 10 consecutive days.

      Pain will be assessed, and quality of life will be investigated using standardized and
      validated questionnaires [Pain Intensity Numerical Rating Scale (PI-NRS), patient global
      impression of change (PGIC), neuropathic pain symptom inventory (NPSI) questionnaire, daily
      sleep interference scale (DSIS) score, hospital anxiety and depression scale (HADS)].
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: placebo controlled, Phase IIa clinical trial
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from Baseline to Day 10 in the 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS; ranges from "no pain" = 0 to "the worst possible pain" = 10; the lower the score, the better the outcome)
time frame: Baseline to Day 10
description: The 5-day average pain intensity score based on the Pain Intensity Numerical Rating Scale (PI-NRS) will be assessed to investigate the efficacy of repeat oral dosing of AP-325
measure: Longitudinal analysis of the 5-day average PI-NRS score (ranges from "no pain" = 0 to "the worst possible pain" = 10; the lower the score, the better the outcome) over time from Baseline until Day 35
time frame: Baseline to Day 35
description: The 5-day average PI-NRS score will be assessed to investigate the long-lasting efficacy of repeat oral dosing of AP-325 on neuropathic pain over the entire study duration
measure: Changes from Baseline in the 5-day average PI-NRS score (change can be in the range of 0 to 10; the bigger the change towards lower PI-NRS scores, the better the outcome) (from Baseline to Day 5, 15, 20, 25, 30 and 35)
time frame: Baseline to Day 5, 15, 20, 25, 30 and 35
description: The 5-day average PI-NRS score will be assessed
measure: Responder rate: proportion of subjects who have a ≥30% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)
time frame: Baseline to Day 5, 10, 15, 25 and 35
description: The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35
measure: Responder rate: proportion of subjects who have a ≥50% reduction in the 5-day average PI-NRS score (in the range of 0 to 10; the bigger the change towards lower scores, the better the outcome) relative to Baseline (on Days 5, 10, 15, 25 and 35)
time frame: Baseline to Day 5, 10, 15, 25 and 35
description: The responder rate will be compared between treatments on Day 5, 10, 15, 25 and 35
measure: Proportion of subjects who "much improved" or "very much improved" relative to Baseline on the patient global impression of change (PGIC) on Days 3, 10, 15, and 36
time frame: Days 3, 10, 15, and 36
description: The PGIC will be dichotomized into treatment success (i.e. scoring 'much improved' or 'very much improved').
measure: Changes from Baseline in the neuropathic pain evaluation using the neuropathic pain symptom inventory (NPSI; ranges from "no pain" = 0 to "the worst possible pain" = 120; the lower the score, the better) questionnaire on Days 3, 10, 15, and 36
time frame: Baseline, Day 3, 10, 15 and 36
description: Neuropathic pain symptom inventory (NPSI) questionnaire to assess the neuropathic pain of the patients
measure: Changes from Baseline in the 5-day average daily sleep interference scale (DSIS; ranges from "pain does not interfere with sleep" = 0 to "pain completely interferes with sleep" = 10) score (from Baseline to Day 5, 10, 15, 25 and 35)
time frame: Baseline to Day 5, 10, 15, 25 and 35
description: The 5-day average daily sleep interference scale (DSIS) score will be assessed
measure: Changes from Baseline in the anxiety and depression assessment using the hospital anxiety and depression scale (HADS; subscales range from 0 to 21, with higher values indicating higher anxiety or depression; the lower the score) on Days 10 and 36
time frame: Baseline, Day 10 and 36
description: The hospital anxiety and depression scale (HADS) to assess the anxiety and depression of the patients
measure: Time to first use of rescue medication after randomization
time frame: A priori specification not possible, between Day 1 until Day 36
description: The time to first use of rescue medication after randomization will be analyzed
measure: Total amount of rescue medication use (in mg per day) after randomization
time frame: A priori specification not possible, between Day 1 until Day 36
description: The total amount of rescue medication (i.e. the total mg of rescue medication per day will be tabulated
measure: Proportion of subjects classified as treatment failure
time frame: A priori specification not possible, between Day1 and Day 36
description: Proportion of subjects classified as treatment failure at least once after randomization will be tabulated
measure: Time to classification as treatment failure after randomization
time frame: A priori specification not possible, between Day1 and Day 36
description: Time to first classification as treatment failure after randomization will be analyzed
measure: Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)
time frame: A priori specification not possible, between Day1 and Day 36
description: All TEAEs occurring during the clinical trial will be registered, documented and evaluated
measure: Incidence of abnormal physical examinations
time frame: Baseline, Day 3, 10, 15 and 36
description: Abnormal physical examination results will be evaluated and reported as AEs
measure: Changes from Baseline in vital signs: Systolic and diastolic blood pressure
time frame: Baseline, Day 1, 3, 10, 15 and 36
description: Systolic and diastolic blood pressure will be measured
measure: Changes from Baseline in vital signs: Heart rate
time frame: Baseline, Day 1, 3, 10, 15 and 36
description: Heart rate will be measured
measure: Changes from Baseline in vital signs: Respiratory rate
time frame: Baseline, Day 1, 3, 10, 15 and 36
description: Respiratory rate will be measured
measure: Changes from Baseline in vital signs: Aural body temperature
time frame: Baseline, Day 1, 3, 10, 15 and 36
description: Aural body temperature will be measured
measure: Incidence of abnormal laboratory test results
time frame: Baseline, Day 3, 10, 15 and 36
description: Abnormal laboratory test results will be evaluated
measure: Incidence of abnormal ECG readings
time frame: Baseline, Day 3, 10 and 36
description: Abnormal 12 lead ECG readings will be evaluated
measure: Changes from Baseline in body weight
time frame: Baseline, Day 10 and 36
description: Body weight will be evaluated
measure: Plasma concentrations of AP-325 at 1 hour post-dose on Days 1 and 10; pre-dose on Days 3 and 10; and on Day 36
time frame: Days 1, 3, 10 and 36
description: Plasma concentrations of AP-325 will be evaluated
measure: Accumulation of Ctrough from Day 3 to Day 10
time frame: Day 3 and 10
description: Plasma concentrations of AP-325 will be evaluated
measure: Correlation between Ctrough-ss (Day 10) and the change from Baseline to Day 10 in the 5-day average pain intensity score based on the PI-NRS
time frame: Baseline to Day 10
description: AP-325 concentration-effect relationships will be evaluated
measure: Correlation between CYP2C9 genotype and the metabolism of AP-325 (optional)
time frame: Day 3
description: The effect of CYP2C9 polymorphisms (determined by CYP2C9 genotyping) on the plasma concentration of AP-325 will be evaluated
arm group label: AP-325
arm group type: Experimental
description: 25 mg capsule for oral use, 4 capsules (100 mg) once daily in the morning before meals
arm group label: Placebo
arm group type: Placebo Comparator
description: 4 capsules once daily in the morning before meals
intervention type: Drug
intervention name: AP-325
description: During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.
arm group label: AP-325
intervention type: Drug
intervention name: Placebo
description: During the 10-day double-blind treatment period (Days 1 to 10), subjects will take 4 capsules of the IMP orally once daily in the morning before breakfast.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Heike Rittner, Prof. Dr.
role: Principal Investigator
affiliation: Universitätsklinikum Würzburg, Interdisziplinäre Schmerzmedizin, Germany
last name: Guido Koopmans
phone: +49 211 617851
phone ext: 0
email: info@algiax.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Terminated
facility: 
status: Withdrawn
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Withdrawn
facility: 
status: Terminated
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Terminated
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Czechia
country: Germany
country: Spain
responsible party type: Sponsor
mesh term: Neuralgia
sharing ipd: No