<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/NCT04418466</url>
  </required_header>
  <id_info>
    <org_study_id>DLP-114-03</org_study_id>
    <secondary_id>R44MH094036</secondary_id>
    <nct_id>NCT04418466</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant</brief_title>
  <acronym>DLP-114</acronym>
  <official_title>Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant (DLP-114)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Delpor, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Delpor, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety,&#xD;
      Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant&#xD;
      (DLP-114).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase 1 open-label study in stable schizophrenia patients designed to evaluate the safety,&#xD;
      tolerability, and PK of switching from 2 mg/day or 3 mg/day oral risperidone to two DLP-114&#xD;
      devices for a six or twelve-month dosing period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Actual">February 10, 2023</completion_date>
  <primary_completion_date type="Actual">February 10, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>6-12 months</time_frame>
    <description>Determine the number and percent of patients experiencing a treatment-emergent adverse event;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Local Tolerance</measure>
    <time_frame>6-12 months</time_frame>
    <description>Evaluate the incidence of local site reactions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability of Implantation and Explantation Procedures</measure>
    <time_frame>6-12 months</time_frame>
    <description>Assess the incidence of local site reactions and/or Adverse Events (AEs) reported during the implantation and explantation procedures</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral Pharmacokinetic (PK) Profile</measure>
    <time_frame>24 hours</time_frame>
    <description>Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following repeated oral administrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implant Pharmacokinetic (PK) Profile</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following switch from oral risperidone to subcutaneous implantation of two DLP-114 devices.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive and Negative Syndrome Scale (PANSS)</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Measure exploratory treatment outcomes using the 30-item Positive and Negative Syndrome Scale (PANSS). The PANSS provides a total score (sum of the scores of all 30 items) ranging from 30 to 210, higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression-Improvement (CGI-I) Scale</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Measure exploratory treatment outcomes using the CGI-I scale. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mass Balance</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Measure the amount of risperidone drug substance remaining in the DLP-114 reservoir following its removal, in order to estimate average daily output and duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implant device placement depth</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Determine average depth of implant device placement measured by ultrasound in mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine potential implant migration</measure>
    <time_frame>6-12 Months</time_frame>
    <description>Migration measured by the distance between the incision and the proximal end of the implant device</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>DLP-114 alpha-4 (6-months)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 360mg Risperidone Implants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DLP-114 alpha-7 (12-months)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 435mg Risperidone Implants</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Risperidone</intervention_name>
    <description>Risperidone Implant</description>
    <arm_group_label>DLP-114 alpha-4 (6-months)</arm_group_label>
    <arm_group_label>DLP-114 alpha-7 (12-months)</arm_group_label>
    <other_name>DLP-114</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients 18-70 years of age of both sexes diagnosed with schizophrenia or&#xD;
             schizoaffective disorder according to DSM-V who have been stable on oral risperidone&#xD;
             (2mg-3mg) for at least 2 weeks.&#xD;
&#xD;
          2. Patient (and/or a patient's authorized legal representative) has provided written&#xD;
             informed consent&#xD;
&#xD;
          3. Patient meets the following criteria:&#xD;
&#xD;
               1. Outpatient status&#xD;
&#xD;
               2. PANSS Total Score ≤ 80 at screening.&#xD;
&#xD;
               3. A score of ≤ 4 on the following PANSS items:&#xD;
&#xD;
             i. Conceptual disorganization ii. Suspiciousness iii. Hallucinatory behavior iv.&#xD;
             Unusual thought content v. Hostility d. CGI-I-S ≤ 4 (moderately ill)\Lack of&#xD;
             clinically significant suicidal ideation or behavior; C-SSRS score type of 4-5 require&#xD;
             evaluation by mental health professional to ensure patient safety in study&#xD;
&#xD;
          4. Body Mass Index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive);&#xD;
&#xD;
          5. Ability to understand the nature and objectives of the trial, including risks and&#xD;
             adverse events, and be able to read, review and sign the informed consent document&#xD;
             prior to conduct of any study procedures;&#xD;
&#xD;
          6. Willing and able to comply with the requirements of the study protocol; including&#xD;
             willingness to visit the clinical facility for all outpatient visits and confinement&#xD;
             periods;&#xD;
&#xD;
          7. Have suitable venous access for blood sampling.&#xD;
&#xD;
          8. Patient is assessed by the Investigator to be symptomatically stable with regard to&#xD;
             pre-existing medical conditions as evidenced by medical history, non-clinically&#xD;
             significant findings on physical examination, vital signs, clinical laboratory&#xD;
             evaluations (hematology, serum chemistries, and urinalysis) or 12-lead&#xD;
             electrocardiogram (ECG). Subjects may continue on their current prescribed medication&#xD;
             regimens to control pre-existing medical and psychiatric conditions (other than&#xD;
             schizophrenia) including the use of prescribed PRN medications.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. PANSS score at baseline is ≥ 20% change from screening.&#xD;
&#xD;
          2. Hospitalized or required acute crisis intervention for symptom exacerbation in the 60&#xD;
             days prior to admission as determined by the Investigator&#xD;
&#xD;
          3. Patient has a history of suicide attempt in the last year, or in the opinion of the&#xD;
             investigator is currently at imminent risk of suicide.&#xD;
&#xD;
          4. Patient experiencing acute depressive symptoms within the past 30 days, according to&#xD;
             the Investigator's opinion, that required treatment with an antidepressant&#xD;
&#xD;
          5. Has a current or recent (within 12 months) DSM-V diagnosis of moderate or severe&#xD;
             substance use disorder (except for tobacco use disorder) or has a positive urine drug&#xD;
             screen for prohibited substances at screening.&#xD;
&#xD;
          6. Have impaired hepatic (ALT/AST &gt;1.5 times higher than the upper limit of normal) or&#xD;
             renal function (eGFR&lt;50 mL/min)&#xD;
&#xD;
          7. Previously defined hypersensitivity to Risperidone&#xD;
&#xD;
          8. History of neuroleptic malignant syndrome (NMS)&#xD;
&#xD;
          9. Electroconvulsive therapy within 6 months of admission&#xD;
&#xD;
         10. Requires current use of agents that are strong inhibitors and inducers of cytochrome&#xD;
             P450;&#xD;
&#xD;
         11. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the&#xD;
             amide type (local anesthetic used during implant and explant procedures);&#xD;
&#xD;
         12. Presence of clinically significant skin disorders (such as, but not limited to, skin&#xD;
             cancer, psoriasis, eczema, or atopic dermatitis), evidence of recent sunburn, scar&#xD;
             tissue, tattoo, open sore, body piercing or branding at the intended implantation site&#xD;
             that would interfere with the implantation procedure or interfere with implant site&#xD;
             assessments as determined by the investigator;&#xD;
&#xD;
         13. History of clinically significant hypersensitivity or allergic reactions;&#xD;
&#xD;
         14. Known allergy or hypersensitivity to PABA;&#xD;
&#xD;
         15. Known allergy or hypersensitivity to parabens, local anesthetics of the ester type,&#xD;
             and sulfa drugs including antibiotics and thiazide diuretics;&#xD;
&#xD;
         16. Known hypersensitivity to titanium, implant materials or procedure;&#xD;
&#xD;
         17. Administration of an investigational drug or device within 1 month prior to first&#xD;
             dosing;&#xD;
&#xD;
         18. Positive result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody,&#xD;
             or HIV antibody;&#xD;
&#xD;
         19. Pregnant or lactating patients. Positive pregnancy test;&#xD;
&#xD;
         20. Positive drug test for Methamphetamines, Opiates, Cocaine, Phencyclidine,&#xD;
             Benzodiazepines, Barbiturates, Methadone, Antidepressants and Amphetamines or positive&#xD;
             alcohol test at screening or prior to first dose;&#xD;
&#xD;
         21. Poor CYP2D6 metabolizer;&#xD;
&#xD;
         22. History of skin picking or delusional parasitosis;&#xD;
&#xD;
         23. Known history of abnormal scar formation or family history of keloid formation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Collaborative Neuroscience Research</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Segal Trials</name>
      <address>
        <city>Miami Lakes</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>February 24, 2023</last_update_submitted>
  <last_update_submitted_qc>February 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>risperidone</keyword>
  <keyword>schizophrenia</keyword>
  <keyword>implant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Risperidone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04418466
org study id: DLP-114-03
secondary id: R44MH094036
nct id: NCT04418466
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
This is an Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety,
      Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant
      (DLP-114).
Phase 1 open-label study in stable schizophrenia patients designed to evaluate the safety,
      tolerability, and PK of switching from 2 mg/day or 3 mg/day oral risperidone to two DLP-114
      devices for a six or twelve-month dosing period.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: 6-12 months
description: Determine the number and percent of patients experiencing a treatment-emergent adverse event;
measure: Local Tolerance
time frame: 6-12 months
description: Evaluate the incidence of local site reactions
measure: Tolerability of Implantation and Explantation Procedures
time frame: 6-12 months
description: Assess the incidence of local site reactions and/or Adverse Events (AEs) reported during the implantation and explantation procedures
measure: Oral Pharmacokinetic (PK) Profile
time frame: 24 hours
description: Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following repeated oral administrations
measure: Implant Pharmacokinetic (PK) Profile
time frame: 6-12 Months
description: Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following switch from oral risperidone to subcutaneous implantation of two DLP-114 devices.
measure: Positive and Negative Syndrome Scale (PANSS)
time frame: 6-12 Months
description: Measure exploratory treatment outcomes using the 30-item Positive and Negative Syndrome Scale (PANSS). The PANSS provides a total score (sum of the scores of all 30 items) ranging from 30 to 210, higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology)
measure: Clinical Global Impression-Improvement (CGI-I) Scale
time frame: 6-12 Months
description: Measure exploratory treatment outcomes using the CGI-I scale. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
measure: Mass Balance
time frame: 6-12 Months
description: Measure the amount of risperidone drug substance remaining in the DLP-114 reservoir following its removal, in order to estimate average daily output and duration
measure: Implant device placement depth
time frame: 6-12 Months
description: Determine average depth of implant device placement measured by ultrasound in mm
measure: Determine potential implant migration
time frame: 6-12 Months
description: Migration measured by the distance between the incision and the proximal end of the implant device
arm group label: DLP-114 alpha-4 (6-months)
arm group type: Experimental
description: 2 360mg Risperidone Implants
arm group label: DLP-114 alpha-7 (12-months)
arm group type: Experimental
description: 2 435mg Risperidone Implants
intervention type: Combination Product
intervention name: Risperidone
description: Risperidone Implant
arm group label: DLP-114 alpha-4 (6-months)
arm group label: DLP-114 alpha-7 (12-months)
other name: DLP-114
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Risperidone