PH94B Nasal Spray for Anxiety Induced by a Public Speaking Challenge

Study Overview
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Brief Summary
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This Phase 3 clinical trial is designed to evaluate the efficacy, safety, and tolerability of the acute administration of 3.2 µg of PH94B to relieve symptoms of anxiety in adult subjects with social anxiety disorder (SAD) during an induced public speaking challenge. Subject participation in the Study will last a total of 3 to 7 weeks, depending on the duration of the screening period and intervals between visits. Upon signing an informed consent, all subjects will complete Visit 1 (Screening) and enter a screening period lasting between 3 and 35 days. If subjects meet all eligibility criteria at the end of the screening period, subjects will return for Visit 2 and self-administer the nasal spray and then participate in a 5 minute public speaking challenge. During the public speaking challenge, the subject will be asked for their anxiety score, which will be recorded by a trained observer. At Visit 3, the subjects will undergo the same public speaking procedure once again as they did in Visit 2. One week after the completion of the Visit 3 public speaking challenge, the subject will come back for Visit 4 (Follow-up) that will involve a repeat of the safety and psychiatric assessments conducted at Screening.

Official Title
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A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial of PH94B Nasal Spray for the Acute Treatment of Anxiety Induced by a Public Speaking Challenge in Adult Subjects With Social Anxiety Disorder

Conditions
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Social Anxiety Disorder

Intervention / Treatment
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* Drug: PH94B Nasal Spray
* Drug: Placebo Nasal Spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided prior to conducting any study-specific assessment. Male or female adult, 18 through 65 years of age, inclusive. Current diagnosis of SAD as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, as confirmed by the Mini-International Neuropsychiatric Interview (MINI). Clinician-rated Liebowitz Social Anxiety Scale (LSAS) total score ≥70 at Screening (Visit 1). Clinician-rated Hamilton Depression Score 17-items total score <18 at Screening (Visit 1). Women of child bearing-potential must be able to commit to the consistent and correct use of an effective method of birth control throughout the study, and must also have a negative urine pregnancy test result at both Screening (Visit 1) and Baseline (Visit 2), prior to IP administration. Effective methods of contraception include: condoms with spermicide, diaphragm with spermicide, hormonal contraceptive agents (oral, transdermal, or injectable), or implantable contraceptive devices. Negative COVID-19 test either in the presence of COVID-19 symptoms or after direct exposure to someone with a positive COVID-19 test. Exclusion Criteria: Any history of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, psychosis, anorexia or bulimia, premenstrual dysphoric disorder, or obsessive-compulsive disorder. Any other current Axis I disorder, other than SAD, which is the primary focus of treatment. Note that subjects with concurrent Generalized Anxiety Disorder are eligible for the study provided that Generalized Anxiety Disorder is not the primary diagnosis. Subjects who meet criteria for moderate or severe alcohol or substance use disorder within the 1 year prior to Study entry. In the opinion of the investigator, the subject has a significant risk for suicidal behavior during the course of their participation in the study, or considered to be an imminent danger to themselves or others. Clinically significant nasal pathology or history of significant nasal trauma, nasal surgery, anosmia, or nasal septum perforation that may have damaged the nasal chemosensory epithelium. An acute or chronic condition, including an infectious illness, uncontrolled seasonal allergies at the time of the study, or significant nasal congestion that potentially could affect drug delivery to the nasal chemosensory epithelium. Two or more documented failed treatment trials with a registered medication approved for SAD, taken at any time during the lifetime of the patient, whereby an adequate treatment trial is defined as that documented in the package insert for a particular drug during which the subject received an adequate medication dosage (defined as the treatment dose indicated in the package insert to obtain efficacy for that particular drug). Use of any psychotropic medication within 30 days before Study entry (other than allowed medication for insomnia. Concomitant use of any anxiolytics, such as benzodiazepines or unapproved treatments such as beta blockers, during the Study and within 30 days before Study entry. Concomitant use of any over-the-counter, prescription product, or herbal preparation for treatment of the symptoms of anxiety or social anxiety during the Study and within 30 days before Study entry. Prior participation in a clinical trial involving PH94B. Women who have a positive serum or urine pregnancy test prior to IP administration. Subjects with clinically significant abnormalities in hematology, blood chemistry, urinalysis, electrocardiogram, or physical examination identified at the Screening visit or Baseline visit that in the clinical judgment of the Investigator, could place the subject at undue risk, interfere with study participation, or confound the results of the study. Subjects with a positive urine drug screen at either the Screening visit or Baseline visit (not including tetrahydrocannabinol). Any current clinically significant and/or uncontrolled medical condition, based on medical history or as evidenced in screening assessments, such as SARS-Cov-2, HIV, cancer, stroke, congestive heart failure, uncontrolled diabetes mellitus, or any other medical condition or disease that, in the clinical judgment of the Investigator, could place the subject at undue risk, interfere with Study participation, or confound the results of the Study. History of cancer or malignant tumor not in remission for at least 2 years. Basal cell skin cancers are not exclusionary.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PH94B<br>3.2 micrograms PH94B intranasal spray (100 microliters to each nostril) one time | Drug: PH94B Nasal Spray<br>* Nasal spray delivered 20 minutes before the public speaking stressor<br>|
| Experimental: Placebo<br>Placebo intranasal spray (100 microliters to each nostril) one time | Drug: Placebo Nasal Spray<br>* Nasal spray delivered 20 minutes before the public speaking stressor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Units of Distress Scale (SUDS) | 0-100 self-report scale of level of anxiety | 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Improvement | Investigator-reported impression | 20 minutes |