<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/NCT04435431</url>
  </required_header>
  <id_info>
    <org_study_id>IRL790C005</org_study_id>
    <nct_id>NCT04435431</nct_id>
  </id_info>
  <brief_title>A Clinical Study of Mesdopetam in Patients With Parkinson's Disease Experiencing Levodopa Induced Dyskinesia</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Phase IIB Study Evaluating the Efficacy of Mesdopetam on Daily ON-time Without Troublesome Dyskinesia in Patients With Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Integrative Research Laboratories AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Integrative Research Laboratories AB</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2b study investigating the efficacy and safety of mesdopetam as adjunct&#xD;
      therapy on daily ON-time without troublesome dyskinesia in patients with Parkinson disease.&#xD;
      Mesdopetam is taken for 84 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At the screening visit consenting patients will be screened for eligibility according to&#xD;
      study specific inclusion/exclusion criteria within 8 weeks before start of Investigational&#xD;
      Medicinal Product (IMP) administration. A diary concordance training will be performed and&#xD;
      following the screening visit the patient will be asked to self-administer three 24-hour home&#xD;
      diaries and to bring the completed diaries to the baseline visit for assessment prior&#xD;
      randomization.&#xD;
&#xD;
      At the baseline visit, patients will be randomized to receive one of three doses of&#xD;
      mesdopetam (dose 1, dose 2 and dose 3) or placebo b.i.d.&#xD;
&#xD;
      During the first week a dose run-in phase will take place, where all patients allocated to&#xD;
      mesdopetam will receive a run-in dose of mesdopetam twice daily and patients allocated to&#xD;
      placebo will receive placebo twice daily. At Visit 2, patients will receive mesdopetam dose&#xD;
      1, dose 2 or dose 3 or placebo b.i.d., as randomized and continue the same dose for the rest&#xD;
      of the treatment period until EOT. Dose reductions are restricted and the dose can only be&#xD;
      reduced once. Dose reductions are permitted from visit 2 (day 9) until visit 3 (day 28),&#xD;
      where after the dose should be kept stable until EOT.&#xD;
&#xD;
      The treatment allocation will be double-blind, i.e. it will not be disclosed to the patients,&#xD;
      the site staff or the Sponsor.&#xD;
&#xD;
      During the treatment period, changes in disease state and ON phase dyskinesia will be&#xD;
      assessed using the MDS-UPDRS, the modified UDysRS (i.e. parts 1, 3 and 4), and Clinician's&#xD;
      Global Impression of Severity (CGI-S). Furthermore, patients will self-administer three&#xD;
      24-hour home diaries prior to visit 3 (week 4), visit 4 (week 8) and visit 5 (week 12) to&#xD;
      assess daily motor function.&#xD;
&#xD;
      Blood samples for pharmacokinetic (PK) analysis will be collected at visit 4 (week 8) and&#xD;
      visit 5 (week 12).&#xD;
&#xD;
      Visit 6 (follow-up) will be performed for all patients, including any patients that&#xD;
      discontinue the IMP early, 5-8 days after last administration of IMP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 29, 2020</start_date>
  <completion_date type="Actual">December 9, 2022</completion_date>
  <primary_completion_date type="Actual">December 2, 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>Change in average daily hours of ON-time without troublesome dyskinesia with mesdopetam compared to Placebo as assessed with 24-hour patient home diaries from baseline to end of treatment.</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in mean score of ON-phase dyskinesia assessed with the sum score of the modified UDysRS (parts 1, 3 and 4) (with mesdopetam compared to placebo).</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>The scoring range is 0-88, where higher score means more dyskinesia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in mean score of disability associated with ON-phase dyskinesia assessed with the sum score of parts 1b and 4 of the UDysRS (with mesdopetam compared to placebo).</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>The scoring range is 0-60, where higher score means more dyskinesia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in mean score of ON-phase dyskinesia assessed by MDS-UPDRS part 4 questions 4.1 (Time spent with dyskinesias) and 4.2 (Functional impact of dyskinesias) (with mesdopetam compared to placebo).</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>Minimum score is 0 and maximum score is 8. A higher score means more dyskinesia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in mean score of motor symptoms of PD assessed with MDS-UPDRS total score of part 2 (M-EDL) (with mesdopetam compared to placebo)</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>Minimum score is 0 and maximum score is 52. A higher score means more motor symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in average daily hours of OFF-time, daily ON-time with troublesome dyskinesia and daily total ON-time (defined as the sum of ON-time with and without troublesome dyskinesia) (with mesdopetam compared to placebo).</measure>
    <time_frame>Baseline to end of treatment (week 12)</time_frame>
    <description>This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">156</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Mesdopetam dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mesdopetam capsule (mg), dose 1, 1 capsule b.i.d. for 84 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mesdopetam dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mesdopetam capsule (mg), dose 2, 1 capsule b.i.d. for 84 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mesdopetam dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mesdopetam capsule (mg), dose 3, 1 capsule b.i.d. for 84 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsule, 1 capsule b.i.d. for 84 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesdopetam</intervention_name>
    <description>Oral use</description>
    <arm_group_label>Mesdopetam dose 1</arm_group_label>
    <arm_group_label>Mesdopetam dose 2</arm_group_label>
    <arm_group_label>Mesdopetam dose 3</arm_group_label>
    <other_name>IRL790</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral use</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥30 and ≤79 years of age at the time of screening.&#xD;
&#xD;
          2. Signed a current Ethics Committee approved informed consent form (ICF).&#xD;
&#xD;
          3. PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic&#xD;
             Criteria.&#xD;
&#xD;
          4. Minimal amount of 2 hours of levodopa-induced daily &quot;ON-time with troublesome&#xD;
             dyskinesia&quot; during waking hours&#xD;
&#xD;
          5. Functional impact of dyskinesias determined as a score of ≥2 as per Question 4.2 of&#xD;
             the MDS-UPDRS.&#xD;
&#xD;
          6. On a stable regimen of antiparkinson medications for at least 30 days prior to first&#xD;
             home diary completion which must include a levodopa preparation administered 3-8&#xD;
             times/day (excluding nighttime levodopa) and willing to continue the same doses and&#xD;
             regimens during study participation. Rescue medications such as Madopar dispersable&#xD;
             and Apomorphine injections are allowed if prescribed PRN prior to study entry.&#xD;
&#xD;
          7. Any other current and allowed prescription/non-prescription medications and/or&#xD;
             nutritional supplements taken regularly must have been at a stable dose and regimen&#xD;
             for at least 30 days prior to first home diary completion and the patient must be&#xD;
             willing to continue the same doses and regimens during study participation (this&#xD;
             criterion does not apply to medications that are being taken pre-study only on an&#xD;
             as-needed basis).&#xD;
&#xD;
          8. Able to complete 24-hour patient home diaries of which two valid diaries must be&#xD;
             presented at visit 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of neurosurgical intervention related to PD (e.g. deep brain stimulation).&#xD;
&#xD;
          2. Treatment with pump delivered antiparkinsonian therapy (i.e. subcutaneous apomorphine&#xD;
             or levodopa/carbidopa intestinal infusion).&#xD;
&#xD;
          3. History of seizures within two years prior to screening.&#xD;
&#xD;
          4. History of stroke or transient ischemic attack (TIA) within two years prior to&#xD;
             screening.&#xD;
&#xD;
          5. History of cancer within five years prior to screening, with the following exceptions:&#xD;
             adequately treated non-melanomatous skin cancers, localized bladder cancer, non&#xD;
             metastatic prostate cancer or in situ cervical cancer.&#xD;
&#xD;
          6. Presence of cognitive impairment, as evidenced by a Mini-Mental State Examination&#xD;
             (MMSE) score of less than 24 during screening.&#xD;
&#xD;
          7. A Hoehn and Yahr stage of 5.&#xD;
&#xD;
          8. Ongoing treatment with amantadine at time of screening or within 6 weeks prior first&#xD;
             home diary completion.&#xD;
&#xD;
          9. Treatment with Inbrija (levodopa inhalation powder) at time of screening or within 4&#xD;
             weeks prior first home diary completion.&#xD;
&#xD;
         10. Any history of a significant heart condition or cardiac arrhythmias within the past 5&#xD;
             years, any repolarisation deficits or any other clinically significant abnormal ECG as&#xD;
             judged by the Investigator.&#xD;
&#xD;
         11. Severe or ongoing unstable medical condition including a history of poorly controlled&#xD;
             diabetes; obesity associated with metabolic syndrome; uncontrolled hypertension;&#xD;
             cerebrovascular disease, or any form of clinically significant cardiac disease,&#xD;
             clinically significant symptomatic orthostatic hypotension (a fall and/or a&#xD;
             discomfort); clinically significant hepatic disease, severe renal impairment, i.e.&#xD;
             creatinine clearance &lt;30 mL/min (stage IV or V).&#xD;
&#xD;
         12. Any history of a neurological disorder other than PD or a psychiatric disorder,&#xD;
             including history of Diagnostic and Statistical Manual of Mental Disorders (DSM) IV&#xD;
             diagnosed major depression or psychosis. Patients with illusions or hallucinations&#xD;
             with no loss of insight will be eligible. Patients with mild depression who are well&#xD;
             controlled on a stable dose of an antidepressant medication for at least 4 weeks&#xD;
             before screening will be eligible.&#xD;
&#xD;
         13. Enrolment in any other clinical study involving medication, medical devices or&#xD;
             surgical procedures, current or within three months prior to screening visit, or&#xD;
             previous participation in the present study. Patients enrolled in non-interventional&#xD;
             clinical trials will be eligible.&#xD;
&#xD;
         14. Drug and/or alcohol abuse.&#xD;
&#xD;
         15. History of severe drug allergy or hypersensitivity.&#xD;
&#xD;
         16. If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose.&#xD;
&#xD;
         17. Patients unwilling to use two forms of contraception (one of which being a barrier&#xD;
             method (see Section 8.1) during the treatment period and 90 days for men and 30 days&#xD;
             for women after last IMP dose.&#xD;
&#xD;
         18. Any planned major surgery within the duration of the study.&#xD;
&#xD;
         19. Any other condition or symptoms preventing the patient from entering the study,&#xD;
             according to the Investigator's judgement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joakim Tedroff</last_name>
    <role>Study Director</role>
    <affiliation>Integrative Research Laboratories AB (IRLAB)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Movement Disorders Center of Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Research (CNS Research)</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center of Silicon Valley</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Springs Neurological Associates</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center of Boca Raton</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Life Medical Research Group Corp</name>
      <address>
        <city>Miami Gardens</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avantis Clinical Research</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elias Research Associates (Allied Biomedical Research Institute)</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pharmax Research of South Florida, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NeuroStudies.net, LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky, Department of Neurology</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Movement Disorder Clinic of Oklahoma</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inland Northwest Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Regional Universitaire de Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dupuytren 1 - Neurologie</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Carémeau</name>
      <address>
        <city>Nimes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rennes-Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Charles Nicolle; Service de Neurologie</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care Campus, Department of Neurology</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah University Hospital-Ein Kerem, Department of Neurology</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Centre - Beilinson Hospital, Department of Neurology</name>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Chaim Sheba Medical Centre, Department of Neurology</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5265601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Centre; Movement Disorders Unit</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS - Ospedale &quot;San Martino&quot;</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Padova</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS San Raffaele Pisana</name>
      <address>
        <city>Roma</city>
        <zip>00163</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU San Giovanni di Dio e Ruggi d'Aragona, Clinica Neurologica</name>
      <address>
        <city>Salerno</city>
        <zip>84131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Neuromed</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-163</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjalistyczna Praktyka Lekarska</name>
      <address>
        <city>Katowice</city>
        <zip>40-097</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne PLEJADY</name>
      <address>
        <city>Kraków</city>
        <zip>30-363</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjalistyczne Gabinety Sp z o.o.</name>
      <address>
        <city>Kraków</city>
        <zip>30-539</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krakowska Akademia Neurologii</name>
      <address>
        <city>Kraków</city>
        <zip>31-505</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Zdrowia</name>
      <address>
        <city>Oświęcim</city>
        <zip>32-600</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuro-Care</name>
      <address>
        <city>Siemianowice Śląskie</city>
        <zip>41-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Next Stage sp.z o.o.</name>
      <address>
        <city>Warsaw</city>
        <zip>02-042</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne NeuroProtect</name>
      <address>
        <city>Warszawa</city>
        <zip>01-684</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinHouse Centrum Medyczne</name>
      <address>
        <city>Zabrze</city>
        <zip>41-807</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Hospital Center Zvezdara, Clinical department of Neurology</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center of Serbia, Clinic for Neurology</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center Kragujevac, Clinic for Neurology (Site 601)</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center Kragujevac, Clinic for Neurology (Site 602)</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Becanovic K, Vittoria de Donno M, Sousa VC, Tedroff J, Svenningsson P. Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission. J Pharmacol Exp Ther. 2020 Jul;374(1):126-133. doi: 10.1124/jpet.119.264754. Epub 2020 May 1.</citation>
    <PMID>32358047</PMID>
  </reference>
  <reference>
    <citation>Waters S, Sonesson C, Svensson P, Tedroff J, Carta M, Ljung E, Gunnergren J, Edling M, Svanberg B, Fagerberg A, Kullingsjo J, Hjorth S, Waters N. Preclinical Pharmacology of [2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl](Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease. J Pharmacol Exp Ther. 2020 Jul;374(1):113-125. doi: 10.1124/jpet.119.264226. Epub 2020 May 1.</citation>
    <PMID>32358046</PMID>
  </reference>
  <reference>
    <citation>Svenningsson P, Johansson A, Nyholm D, Tsitsi P, Hansson F, Sonesson C, Tedroff J. Safety and tolerability of IRL790 in Parkinson's disease with levodopa-induced dyskinesia-a phase 1b trial. NPJ Parkinsons Dis. 2018 Dec 6;4:35. doi: 10.1038/s41531-018-0071-3. eCollection 2018.</citation>
    <PMID>30534585</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>December 14, 2022</last_update_submitted>
  <last_update_submitted_qc>December 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2022</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>Parkinson Disease</mesh_term>
    <mesh_term>Dyskinesias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesdopetam</mesh_term>
  </intervention_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/NCT04435431
org study id: IRL790C005
nct id: NCT04435431
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2b study investigating the efficacy and safety of mesdopetam as adjunct
      therapy on daily ON-time without troublesome dyskinesia in patients with Parkinson disease.
      Mesdopetam is taken for 84 days.
At the screening visit consenting patients will be screened for eligibility according to
      study specific inclusion/exclusion criteria within 8 weeks before start of Investigational
      Medicinal Product (IMP) administration. A diary concordance training will be performed and
      following the screening visit the patient will be asked to self-administer three 24-hour home
      diaries and to bring the completed diaries to the baseline visit for assessment prior
      randomization.

      At the baseline visit, patients will be randomized to receive one of three doses of
      mesdopetam (dose 1, dose 2 and dose 3) or placebo b.i.d.

      During the first week a dose run-in phase will take place, where all patients allocated to
      mesdopetam will receive a run-in dose of mesdopetam twice daily and patients allocated to
      placebo will receive placebo twice daily. At Visit 2, patients will receive mesdopetam dose
      1, dose 2 or dose 3 or placebo b.i.d., as randomized and continue the same dose for the rest
      of the treatment period until EOT. Dose reductions are restricted and the dose can only be
      reduced once. Dose reductions are permitted from visit 2 (day 9) until visit 3 (day 28),
      where after the dose should be kept stable until EOT.

      The treatment allocation will be double-blind, i.e. it will not be disclosed to the patients,
      the site staff or the Sponsor.

      During the treatment period, changes in disease state and ON phase dyskinesia will be
      assessed using the MDS-UPDRS, the modified UDysRS (i.e. parts 1, 3 and 4), and Clinician's
      Global Impression of Severity (CGI-S). Furthermore, patients will self-administer three
      24-hour home diaries prior to visit 3 (week 4), visit 4 (week 8) and visit 5 (week 12) to
      assess daily motor function.

      Blood samples for pharmacokinetic (PK) analysis will be collected at visit 4 (week 8) and
      visit 5 (week 12).

      Visit 6 (follow-up) will be performed for all patients, including any patients that
      discontinue the IMP early, 5-8 days after last administration of IMP.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in average daily hours of ON-time without troublesome dyskinesia with mesdopetam compared to Placebo as assessed with 24-hour patient home diaries from baseline to end of treatment.
time frame: Baseline to end of treatment (week 12)
description: This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.
measure: Change from baseline in mean score of ON-phase dyskinesia assessed with the sum score of the modified UDysRS (parts 1, 3 and 4) (with mesdopetam compared to placebo).
time frame: Baseline to end of treatment (week 12)
description: The scoring range is 0-88, where higher score means more dyskinesia.
measure: Change from baseline in mean score of disability associated with ON-phase dyskinesia assessed with the sum score of parts 1b and 4 of the UDysRS (with mesdopetam compared to placebo).
time frame: Baseline to end of treatment (week 12)
description: The scoring range is 0-60, where higher score means more dyskinesia.
measure: Change from baseline in mean score of ON-phase dyskinesia assessed by MDS-UPDRS part 4 questions 4.1 (Time spent with dyskinesias) and 4.2 (Functional impact of dyskinesias) (with mesdopetam compared to placebo).
time frame: Baseline to end of treatment (week 12)
description: Minimum score is 0 and maximum score is 8. A higher score means more dyskinesia.
measure: Change from baseline in mean score of motor symptoms of PD assessed with MDS-UPDRS total score of part 2 (M-EDL) (with mesdopetam compared to placebo)
time frame: Baseline to end of treatment (week 12)
description: Minimum score is 0 and maximum score is 52. A higher score means more motor symptoms.
measure: Change from baseline in average daily hours of OFF-time, daily ON-time with troublesome dyskinesia and daily total ON-time (defined as the sum of ON-time with and without troublesome dyskinesia) (with mesdopetam compared to placebo).
time frame: Baseline to end of treatment (week 12)
description: This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.
arm group label: Mesdopetam dose 1
arm group type: Experimental
description: Mesdopetam capsule (mg), dose 1, 1 capsule b.i.d. for 84 days.
arm group label: Mesdopetam dose 2
arm group type: Experimental
description: Mesdopetam capsule (mg), dose 2, 1 capsule b.i.d. for 84 days.
arm group label: Mesdopetam dose 3
arm group type: Experimental
description: Mesdopetam capsule (mg), dose 3, 1 capsule b.i.d. for 84 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo capsule, 1 capsule b.i.d. for 84 days
intervention type: Drug
intervention name: Mesdopetam
description: Oral use
arm group label: Mesdopetam dose 1
arm group label: Mesdopetam dose 2
arm group label: Mesdopetam dose 3
other name: IRL790
intervention type: Drug
intervention name: Placebo
description: Oral use
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 79 Years
healthy volunteers: No
last name: Joakim Tedroff
role: Study Director
affiliation: Integrative Research Laboratories AB (IRLAB)
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country: France
country: Israel
country: Italy
country: Poland
country: Serbia
country: United States
citation: Becanovic K, Vittoria de Donno M, Sousa VC, Tedroff J, Svenningsson P. Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission. J Pharmacol Exp Ther. 2020 Jul;374(1):126-133. doi: 10.1124/jpet.119.264754. Epub 2020 May 1.
PMID: 32358047
citation: Waters S, Sonesson C, Svensson P, Tedroff J, Carta M, Ljung E, Gunnergren J, Edling M, Svanberg B, Fagerberg A, Kullingsjo J, Hjorth S, Waters N. Preclinical Pharmacology of [2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl](Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease. J Pharmacol Exp Ther. 2020 Jul;374(1):113-125. doi: 10.1124/jpet.119.264226. Epub 2020 May 1.
PMID: 32358046
citation: Svenningsson P, Johansson A, Nyholm D, Tsitsi P, Hansson F, Sonesson C, Tedroff J. Safety and tolerability of IRL790 in Parkinson's disease with levodopa-induced dyskinesia-a phase 1b trial. NPJ Parkinsons Dis. 2018 Dec 6;4:35. doi: 10.1038/s41531-018-0071-3. eCollection 2018.
PMID: 30534585
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Dyskinesias
mesh term: Mesdopetam
sharing ipd: No