<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/NCT04404192</url>
  </required_header>
  <id_info>
    <org_study_id>PH94B-CL029</org_study_id>
    <nct_id>NCT04404192</nct_id>
  </id_info>
  <brief_title>PH94B in the Treatment of Adjustment Disorder With Anxiety</brief_title>
  <official_title>A Phase 2a Double-blind, Placebo-controlled, Parallel Study of PH94B Nasal Spray in the Treatment of Adjustment Disorder With Anxiety</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VistaGen Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VistaGen Therapeutics, Inc.</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 placebo-controlled clinical study is designed to evaluate the efficacy, safety and&#xD;
      tolerability of administration of PH94B nasal spray four times per day as a treatment of&#xD;
      Adjustment Disorder with Anxiety symptoms in adults. Subject participation in the Study will&#xD;
      last a total of 6 to 10 weeks, depending on the duration of the screening period and whether&#xD;
      they need a washout of concomitant anxiolytics. Upon signing an investigation review board&#xD;
      approved informed consent, all subjects will complete Visit 1 (Screening) and enter a&#xD;
      screening period lasting 7 to 35 days that could include taper of concomitant anxiolytics, if&#xD;
      necessary. Screening visit will consist of safety assessments (medical history, physical&#xD;
      examination, laboratory samples, electrocardiogram, urine drug screen, and urine pregnancy&#xD;
      test [if appropriate]) and psychiatric assessments to determine eligibility. Subjects will&#xD;
      then return to complete Visit 2 (Baseline). If the subject continues to meet inclusion and&#xD;
      exclusion criteria, the subject will be randomized 1:1 to PH94B or placebo. Subjects will&#xD;
      then commence 4 weeks of double-blind treatment with randomized investigational product&#xD;
      (PH94B or placebo) four times per day.&#xD;
&#xD;
      Subjects will return for weekly site visits (Visits 3, 4, 5, and 6), in which the subject&#xD;
      will return the vial dispensed at the previous visit and receive a new vial, except at Visit&#xD;
      6 in which no new vial will be dispensed. Changes in AEs and concomitant medications will be&#xD;
      collected. During these visits, psychiatric scales will be completed. When the subject&#xD;
      returns for Visit 6, besides the assessments completed at Visits 3 through 5, the subjects&#xD;
      will complete a brief physical examination, electrocardiogram, laboratory tests (chemistry&#xD;
      and blood), and urinalysis. Any remaining IP vials will be collected. The subject will then&#xD;
      come back after a one week washout period for Follow-up visit (Visit 7).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 12, 2021</start_date>
  <completion_date type="Actual">December 14, 2022</completion_date>
  <primary_completion_date type="Actual">December 14, 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hamilton Anxiety Scale</measure>
    <time_frame>28 days</time_frame>
    <description>Questionnaire on anxiety symptoms - change from baseline compared to placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sheehan Disability Scale</measure>
    <time_frame>28 days</time_frame>
    <description>Questionnaire on functioning - change from baseline compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International adjustment disorder questionnaire (IADQ)</measure>
    <time_frame>28 days</time_frame>
    <description>Questionnaire on worrying etc. - change from baseline compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Improvement rating (CGI-I)</measure>
    <time_frame>28 days</time_frame>
    <description>Clinical impression of improvement - change from baseline compared to placebo</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Adjustment Disorder With Anxious Mood</condition>
  <arm_group>
    <arm_group_label>PH94B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intranasal spray 3.2 micrograms four times a day for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intranasal spray four times a day for 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PH94B</intervention_name>
    <description>Intranasal administration of 100 microliters to each nostril 4 times a day</description>
    <arm_group_label>PH94B</arm_group_label>
    <other_name>Aloradine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intranasal administration of 100 microliters to each nostril 4 times a day.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent provided prior to conducting any study-specific assessment.&#xD;
&#xD;
          2. Male and female adults, 18 through 65 years of age, inclusive.&#xD;
&#xD;
          3. Current diagnosis of AjDA as defined in the Diagnostic and Statistical Manual of&#xD;
             Mental Disorders, 5th Edition.&#xD;
&#xD;
          4. Clinician-rated Hamilton Anxiety Scale (HAM-A) score ≥20 at Screening (Visit 1) and no&#xD;
             greater than 15% decrease at Baseline (Visit 2).&#xD;
&#xD;
          5. Clinician-rated Hamilton Depression Scale (HAM-D) total score &lt;18 at Screening (Visit&#xD;
             1) and Baseline (Visit 2).&#xD;
&#xD;
          6. Clinical Global Impression - Severity Scale (CGI-S) score ≥4 at both Screening (Visit&#xD;
             1) and Baseline (Visit 2)&#xD;
&#xD;
          7. Women of child bearing-potential must be able to commit to the consistent and correct&#xD;
             use of an effective method of birth control throughout the Study, and must also have a&#xD;
             negative urine pregnancy test result at both Screening (Visit 1) and Baseline (Visit&#xD;
             2), prior to investigational product (IP) administration. Effective methods of&#xD;
             contraception include: condoms with spermicide, diaphragm with spermicide, hormonal&#xD;
             contraceptive agents (oral, transdermal, or injectable), or implantable contraceptive&#xD;
             devices.&#xD;
&#xD;
          8. Males whose sexual partners are women of childbearing potential must commit to the&#xD;
             consistent and correct use of an effective method of birth control throughout the&#xD;
             study.&#xD;
&#xD;
          9. Negative COVID-19 test either in the presence of COVID-19 symptoms or after exposure&#xD;
             to someone with a positive COVID-19 test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any history of schizophrenia or schizoaffective disorder.&#xD;
&#xD;
          2. Any other current Axis I disorder, including, but not limited to, major depressive&#xD;
             disorder, bipolar disorder, post-traumatic stress disorder, obsessive-compulsive&#xD;
             disorder, premenstrual dysphoric disorder, and generalized anxiety disorder, which is&#xD;
             in poor control and the primary focus of treatment.&#xD;
&#xD;
          3. A diagnosis of social anxiety disorder with a score &gt;60 on the Liebowitz Social&#xD;
             Anxiety Scale.&#xD;
&#xD;
          4. Subjects who meet criteria for moderate or severe alcohol or substance use disorder&#xD;
             within the 1 year prior to Study entry.&#xD;
&#xD;
          5. In the opinion of the investigator, the subject has a significant risk for suicidal&#xD;
             behavior during the course of their participation in the study, or considered to be an&#xD;
             imminent danger to themselves or others.&#xD;
&#xD;
          6. Clinically significant nasal pathology or history of significant nasal trauma, nasal&#xD;
             surgery, anosmia, or nasal septum perforation that may have damaged the nasal&#xD;
             chemosensory epithelium.&#xD;
&#xD;
          7. An acute or chronic condition, including an infectious illness, uncontrolled seasonal&#xD;
             allergies at the time of the study, or significant nasal congestion that potentially&#xD;
             could affect drug delivery to the nasal chemosensory epithelium. The Investigator may&#xD;
             allow concomitant use of over-the-counter nasal decongenstants as needed, since there&#xD;
             is no apparent drug interaction between these and PH94B.&#xD;
&#xD;
          8. Concomitant use of any anxiolytics, such as benzodiazepines or buspirone, during the&#xD;
             Study and within 30 days of Baseline (Visit 2).&#xD;
&#xD;
          9. Concomitant use of any over-the-counter, prescription product, or herbal preparation&#xD;
             for treatment of the symptoms of anxiety during the Study and within 30 days before&#xD;
             Study entry. Selective serotonin reuptake inhibitors, serotonin-norepinephrine&#xD;
             reuptake inhibitors, or other approved antidepressants are permitted as long as the&#xD;
             dose has been stable for 30 days prior to Baseline (Visit 2).&#xD;
&#xD;
         10. Women who have a positive urine or serum pregnancy test at either Screening or&#xD;
             Baseline visit or are currently breast feeding.&#xD;
&#xD;
         11. Subjects with clinically significant abnormalities in hematology, blood chemistry,&#xD;
             urinalysis, electrocardiogram, or physical examination identified at the Screening&#xD;
             visit that in the clinical judgment of the Investigator, could place the subject at&#xD;
             undue risk, interfere with study participation, or confound the results of the study.&#xD;
&#xD;
         12. Subjects with a positive urine drug screen at either the Screening visit or Baseline&#xD;
             visit (not including tetrahydrocannabinol).&#xD;
&#xD;
         13. Any current clinically significant and/or uncontrolled medical condition, based on&#xD;
             medical history or as evidenced in screening assessments, such as SARS-Cov-2, HIV,&#xD;
             cancer, stroke, congestive heart failure, uncontrolled diabetes mellitus, or any other&#xD;
             medical condition or disease that, in the clinical judgment of the Investigator, could&#xD;
             place the subject at undue risk, interfere with Study participation, or confound the&#xD;
             results of the Study.&#xD;
&#xD;
         14. Use of a concomitant medication that, in the clinical judgement of the Investigator,&#xD;
             could place the subject at undue risk, interfere with study participation, or confound&#xD;
             the results of the study.&#xD;
&#xD;
         15. History of cancer or malignant tumor not in remission for at least 2 years. Basal cell&#xD;
             skin cancers are not exclusionary.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>VistaGen Clinical Site</name>
      <address>
        <city>Watertown</city>
        <state>Massachusetts</state>
        <zip>02472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VistaGen Clinical Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 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>Adjustment 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>


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/NCT04404192
org study id: PH94B-CL029
nct id: NCT04404192
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This placebo-controlled clinical study is designed to evaluate the efficacy, safety and
      tolerability of administration of PH94B nasal spray four times per day as a treatment of
      Adjustment Disorder with Anxiety symptoms in adults. Subject participation in the Study will
      last a total of 6 to 10 weeks, depending on the duration of the screening period and whether
      they need a washout of concomitant anxiolytics. Upon signing an investigation review board
      approved informed consent, all subjects will complete Visit 1 (Screening) and enter a
      screening period lasting 7 to 35 days that could include taper of concomitant anxiolytics, if
      necessary. Screening visit will consist of safety assessments (medical history, physical
      examination, laboratory samples, electrocardiogram, urine drug screen, and urine pregnancy
      test [if appropriate]) and psychiatric assessments to determine eligibility. Subjects will
      then return to complete Visit 2 (Baseline). If the subject continues to meet inclusion and
      exclusion criteria, the subject will be randomized 1:1 to PH94B or placebo. Subjects will
      then commence 4 weeks of double-blind treatment with randomized investigational product
      (PH94B or placebo) four times per day.

      Subjects will return for weekly site visits (Visits 3, 4, 5, and 6), in which the subject
      will return the vial dispensed at the previous visit and receive a new vial, except at Visit
      6 in which no new vial will be dispensed. Changes in AEs and concomitant medications will be
      collected. During these visits, psychiatric scales will be completed. When the subject
      returns for Visit 6, besides the assessments completed at Visits 3 through 5, the subjects
      will complete a brief physical examination, electrocardiogram, laboratory tests (chemistry
      and blood), and urinalysis. Any remaining IP vials will be collected. The subject will then
      come back after a one week washout period for Follow-up visit (Visit 7).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Hamilton Anxiety Scale
time frame: 28 days
description: Questionnaire on anxiety symptoms - change from baseline compared to placebo
measure: Sheehan Disability Scale
time frame: 28 days
description: Questionnaire on functioning - change from baseline compared to placebo
measure: International adjustment disorder questionnaire (IADQ)
time frame: 28 days
description: Questionnaire on worrying etc. - change from baseline compared to placebo
measure: Clinical Global Impression - Improvement rating (CGI-I)
time frame: 28 days
description: Clinical impression of improvement - change from baseline compared to placebo
arm group label: PH94B
arm group type: Experimental
description: Intranasal spray 3.2 micrograms four times a day for 28 days
arm group label: Placebo
arm group type: Experimental
description: Intranasal spray four times a day for 28 days
intervention type: Drug
intervention name: PH94B
description: Intranasal administration of 100 microliters to each nostril 4 times a day
arm group label: PH94B
other name: Aloradine
intervention type: Drug
intervention name: Placebo
description: Intranasal administration of 100 microliters to each nostril 4 times a day.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Adjustment Disorders
sharing ipd: No