xml: <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/NCT05976646</url>
    </required_header>
    <id_info>
      <org_study_id>HM20027635</org_study_id>
      <secondary_id>5UG1DA050207</secondary_id>
      <nct_id>NCT05976646</nct_id>
    </id_info>
    <brief_title>Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion</brief_title>
    <official_title>Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (AUVELITY) as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Virginia Commonwealth University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Drug Abuse (NIDA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Virginia Commonwealth University</source>
    <oversight_info>
      <has_dmc>Yes</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>
        The overall goal of this project is to collect initial human data on the effects of novel&#xD;
        compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early&#xD;
        efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in&#xD;
        OUD subjects currently in MOUD treatment with buprenorphine.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The overall goal of this project is to collect initial human data on the effects of novel&#xD;
        compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early&#xD;
        efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in&#xD;
        OUD subjects currently in MOUD treatment with buprenorphine. The compound to be studied in&#xD;
        this protocol will be a pre-configured combination of 45mg dextromethorphan with 105 mg&#xD;
        Bupropion (AuvelityTM, hereafter referred as Auvelity). Notably, other NMDA receptor&#xD;
        antagonists such as ketamine have also been shown to rapidly improve mood and reduce&#xD;
        suicidality. OUD has also been linked to histories of trauma and syndromes of negative mood,&#xD;
        where opioid use in many individuals was initially motivated by a desire to alleviate a&#xD;
        negative mood state. Lastly, using the NIDA Phenotyping Battery, our group has also found&#xD;
        negative emotionality to be part of a constellation of neurofunctional domains that are&#xD;
        associated with SUD severity. Taken together, providing AUVELITY as an adjunctive treatment&#xD;
        to buprenorphine could be an avenue to target crucial underlying mechanisms of OUD and&#xD;
        improve OUD treatment outcomes.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">October 2025</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>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Safety- as measured by heart rate</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours</time_frame>
      <description>Heart rate (HR)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety- as measured by blood pressure</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours</time_frame>
      <description>blood pressure</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety- as measured by pulse oximetry</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours</time_frame>
      <description>pulse oximetry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety- as measured by respiratory rate</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours</time_frame>
      <description>respiratory rate</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety- as measured by Adverse events</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours; and from baseline to end of study participation</time_frame>
      <description>adverse events</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Buprenorphine PK</measure>
      <time_frame>During each PK study visit from visit start to end, up to approximately 8 hours</time_frame>
      <description>Plasma concentration-time profiles of buprenorphine and its metabolite norbuprenorphine</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Addiction</condition>
    <condition>Opioid Use</condition>
    <condition>Substance Use Disorders</condition>
    <condition>Opioid Use Disorder</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Auvelity</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Auvelity</intervention_name>
      <description>Orally-administered combination of 45 mg dextromethorphan with 105 mg Bupropion (trade name Auvelity). Auvelity will initially be administered orally once daily for three days. After 3 days on once daily AUVELITY, the participants will begin taking AUVELITY twice daily for 4 additional days as recommended in the FDA-approved prescribing information.</description>
      <arm_group_label>Auvelity</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Males and female subjects between 18 - 65 years of age;&#xD;
  &#xD;
            -  Understand the study procedures and provide written informed consent in the English&#xD;
               language.&#xD;
  &#xD;
            -  Meet current DSM-5 criteria for OUD, of at least moderate severity, currently engaged&#xD;
               in MOUD treatment at a buprenorphine-naloxone sublingual film total daily dose ranging&#xD;
               from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3&#xD;
               daily for at least 2 weeks at screening. Or on a stable dose of depot injectable&#xD;
               buprenorphine for at least four months, with at least one week since last depot&#xD;
               buprenorphine injection.&#xD;
  &#xD;
            -  Have a positive urine drug screen for buprenorphine during screening and upon&#xD;
               presenting for the first laboratory day on the clinical research unit to document&#xD;
               buprenorphine use;&#xD;
  &#xD;
            -  Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or&#xD;
               greater (&gt;6)&#xD;
  &#xD;
            -  Females must be non-pregnant and non-lactating. Additionally, for females with&#xD;
               childbearing potential (ie., have not undergone sterilization via hysterectomy,&#xD;
               bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year&#xD;
               post-menopausal), participants must agree to use an acceptable form of contraception&#xD;
               during study participation and to continue its use for at least 30 days after the last&#xD;
               dose of the study drug (e.g, abstinence, intrauterine device, hormonal implant,&#xD;
               hormonal patch/ring/pill, condoms (male or female).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Contraindications for participation as determined by medical history and physical exam&#xD;
               performed by study NP or study physician;&#xD;
  &#xD;
            -  Pregnant or nursing women;&#xD;
  &#xD;
            -  Baseline ECG with clinically significant abnormal conduction;&#xD;
  &#xD;
            -  Uncontrolled serious psychiatric or major medical disorder; including uncontrolled&#xD;
               hypertension, seizure disorder, anorexia nervosa or bulimia, bipolar disorder,&#xD;
               schizoaffective disorder, or schizophrenia;&#xD;
  &#xD;
            -  Taking antidepressant medications (tricyclic antidepressants, SSRIs, SNRIs, MAOIs),&#xD;
               antibiotic linezolid, antiepileptics, or CNS stimulants (amphetamine, methylphenidate)&#xD;
               within the two weeks prior to initiation of study medication&#xD;
  &#xD;
            -  History of adverse reaction or allergy to dextromethorphan or bupropion&#xD;
  &#xD;
            -  Current severe alcohol use disorder or current benzodiazepine use or recent (within&#xD;
               last 3 months) discontinuation of alcohol with severe alcohol use disorder or&#xD;
               discontinuation of benzodiazepines with severe benzodiazepine use disorder&#xD;
  &#xD;
            -  Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids,&#xD;
               cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis&#xD;
               of mild to moderate use disorder for alcohol will not be considered exclusionary.&#xD;
  &#xD;
            -  Significant current suicidal or homicidal ideation (C-SSRS &quot;yes&quot; answers on questions&#xD;
               4 or 5) or a history of suicide attempt within the past 6 months.&#xD;
  &#xD;
            -  Any other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
               abnormality that may increase the risk associated with study participation or&#xD;
               investigational product administration or may interfere with the interpretation of&#xD;
               study results and, in the judgment of the investigator, would make the subject&#xD;
               inappropriate for entry into this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Frederick G Moeller</last_name>
      <role>Principal Investigator</role>
      <affiliation>Virginia Commonwealth University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tiffany Pignatello</last_name>
      <phone>804-828-3686</phone>
      <email>Tfitz@vcu.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Kameron Simmons</last_name>
      <phone>804-827-3784</phone>
      <email>simmonsk5@vcu.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Substance-Related Disorders</mesh_term>
      <mesh_term>Opioid-Related Disorders</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05976646
  org study id: HM20027635
  secondary id: 5UG1DA050207
  nct id: NCT05976646
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The overall goal of this project is to collect initial human data on the effects of novel
        compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early
        efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in
        OUD subjects currently in MOUD treatment with buprenorphine.
  The overall goal of this project is to collect initial human data on the effects of novel
        compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early
        efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in
        OUD subjects currently in MOUD treatment with buprenorphine. The compound to be studied in
        this protocol will be a pre-configured combination of 45mg dextromethorphan with 105 mg
        Bupropion (AuvelityTM, hereafter referred as Auvelity). Notably, other NMDA receptor
        antagonists such as ketamine have also been shown to rapidly improve mood and reduce
        suicidality. OUD has also been linked to histories of trauma and syndromes of negative mood,
        where opioid use in many individuals was initially motivated by a desire to alleviate a
        negative mood state. Lastly, using the NIDA Phenotyping Battery, our group has also found
        negative emotionality to be part of a constellation of neurofunctional domains that are
        associated with SUD severity. Taken together, providing AUVELITY as an adjunctive treatment
        to buprenorphine could be an avenue to target crucial underlying mechanisms of OUD and
        improve OUD treatment outcomes.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Safety- as measured by heart rate
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours
  description: Heart rate (HR)
  measure: Safety- as measured by blood pressure
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours
  description: blood pressure
  measure: Safety- as measured by pulse oximetry
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours
  description: pulse oximetry
  measure: Safety- as measured by respiratory rate
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours
  description: respiratory rate
  measure: Safety- as measured by Adverse events
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours; and from baseline to end of study participation
  description: adverse events
  measure: Buprenorphine PK
  time frame: During each PK study visit from visit start to end, up to approximately 8 hours
  description: Plasma concentration-time profiles of buprenorphine and its metabolite norbuprenorphine
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.
  arm group label: Auvelity
  arm group type: Experimental
  description: Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)
  intervention type: Drug
  intervention name: Placebo
  description: Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.
  arm group label: Placebo
  intervention type: Drug
  intervention name: Auvelity
  description: Orally-administered combination of 45 mg dextromethorphan with 105 mg Bupropion (trade name Auvelity). Auvelity will initially be administered orally once daily for three days. After 3 days on once daily AUVELITY, the participants will begin taking AUVELITY twice daily for 4 additional days as recommended in the FDA-approved prescribing information.
  arm group label: Auvelity
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Frederick G Moeller
  role: Principal Investigator
  affiliation: Virginia Commonwealth University
  last name: Tiffany Pignatello
  phone: 804-828-3686
  email: Tfitz@vcu.edu
  last name: Kameron Simmons
  phone: 804-827-3784
  email: simmonsk5@vcu.edu
  responsible party type: Sponsor
  mesh term: Substance-Related Disorders
  mesh term: Opioid-Related Disorders
  sharing ipd: No