Social Anxiety Disorder
Conditions
Brief summary
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.
Interventions
Nasal spray delivered 20 minutes before the public speaking stressor
DRUGPlacebo Nasal Spray
Nasal spray delivered 20 minutes before the public speaking stressor
Sponsors
VistaGen Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent provided prior to conducting any study-specific assessment. 2. Male or female adult, 18 through 65 years of age, inclusive. 3. 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). 4. Clinician-rated Liebowitz Social Anxiety Scale (LSAS) total score ≥70 at Screening (Visit 1). 5. Clinician-rated Hamilton Depression Score 17-items total score \<18 at Screening (Visit 1). 6. 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. 7. 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
1. 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. 2. Subjects who meet criteria for moderate or severe alcohol or substance use disorder within the 1 year prior to Study entry. 3. 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. 4. 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. 5. 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. 6. 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). 7. Use of any psychotropic medication within 30 days before Study entry (other than allowed medication for insomnia. 8. 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. 9. 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. 10. Prior participation in a clinical trial involving PH94B. 11. Women who have a positive serum or urine pregnancy test prior to IP administration. 12. 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. 13. Subjects with a positive urine drug screen at either the Screening visit or Baseline visit (not including tetrahydrocannabinol). 14. 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. 15. History of cancer or malignant tumor not in remission for at least 2 years. Basal cell skin cancers are not exclusionary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Units of Distress Scale (SUDS) Score | Visit 2 (Baseline; Day 0) to Visit 3 (Day 7 ± 2 days) | The SUDS is a patient self-rated scale that is scored in the range of 0 to 100 (operationalized for participants in this study as 0=totally relaxed or no anxiety and 100=highest distress or anxiety ever felt |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportions (%) of CGI-I Responders in PH94B-treated and Placebo-treated Groups at the End of Visit 3 (Treatment) | Visit 2 (Baseline; Day 0) to Visit 3 (Day 7 ± 2 days) | The CGI-I scale is a clinician-rated scale to assess illness improvement. The CGI-I scale includes one item scored from 1 (Very much less anxious) to 7 (Very much more anxious) with 4 being no change. Subjects are considered CGI-I responders with scores of 1 (Very much less anxious) or 2 (Much less anxious |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PH94B 3.2 micrograms PH94B intranasal spray (100 microliters to each nostril) one time
PH94B Nasal Spray: Nasal spray delivered 20 minutes before the public speaking stressor | 112 |
| Placebo Placebo intranasal spray (100 microliters to each nostril) one time
Placebo Nasal Spray: Nasal spray delivered 20 minutes before the public speaking stressor | 112 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | PH94B | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 112 Participants | 224 Participants |
| Age, Continuous | 34.9 years STANDARD_DEVIATION 10.69 | 35.6 years STANDARD_DEVIATION 11.71 | 35.3 years STANDARD_DEVIATION 11.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 3 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 18 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 10 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) White | 63 Participants | 71 Participants | 134 Participants |
| Region of Enrollment United States | 112 participants | 112 participants | 224 participants |
| Sex: Female, Male Female | 77 Participants | 73 Participants | 150 Participants |
| Sex: Female, Male Male | 35 Participants | 39 Participants | 74 Participants |
| Subjective Units of Distress (SUDS) score | 77.7 score on a scale STANDARD_DEVIATION 11.67 | 78.2 score on a scale STANDARD_DEVIATION 12.42 | 77.95 score on a scale STANDARD_DEVIATION 12.05 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 111 | 0 / 112 |
| other Total, other adverse events | 0 / 111 | 0 / 112 |
| serious Total, serious adverse events | 0 / 111 | 0 / 112 |
Outcome results
Primary
Subjective Units of Distress Scale (SUDS) Score
The SUDS is a patient self-rated scale that is scored in the range of 0 to 100 (operationalized for participants in this study as 0=totally relaxed or no anxiety and 100=highest distress or anxiety ever felt
Time frame: Visit 2 (Baseline; Day 0) to Visit 3 (Day 7 ± 2 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PH94B | Subjective Units of Distress Scale (SUDS) Score | Visit 2 | 77.7 score on a scale | Standard Deviation 11.67 |
| PH94B | Subjective Units of Distress Scale (SUDS) Score | Visit 3 | 62.3 score on a scale | Standard Deviation 19.4 |
| Placebo | Subjective Units of Distress Scale (SUDS) Score | Visit 3 | 61.3 score on a scale | Standard Deviation 19.56 |
| Placebo | Subjective Units of Distress Scale (SUDS) Score | Visit 2 | 78.2 score on a scale | Standard Deviation 12.42 |
p-value: 0.506395% CI: [-3.2, 6.4]ANCOVA
Secondary
Proportions (%) of CGI-I Responders in PH94B-treated and Placebo-treated Groups at the End of Visit 3 (Treatment)
The CGI-I scale is a clinician-rated scale to assess illness improvement. The CGI-I scale includes one item scored from 1 (Very much less anxious) to 7 (Very much more anxious) with 4 being no change. Subjects are considered CGI-I responders with scores of 1 (Very much less anxious) or 2 (Much less anxious
Time frame: Visit 2 (Baseline; Day 0) to Visit 3 (Day 7 ± 2 days)
Population: Although the population of analysis included n=112, one subject had no CGI-I value. No imputation was done for secondary endpoints, resulting in n=111 in the denominator.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PH94B | Proportions (%) of CGI-I Responders in PH94B-treated and Placebo-treated Groups at the End of Visit 3 (Treatment) | 34 Participants |
| Placebo | Proportions (%) of CGI-I Responders in PH94B-treated and Placebo-treated Groups at the End of Visit 3 (Treatment) | 36 Participants |
p-value: 0.807795% CI: [-0.137, 0.107]Wald Normal Approximation (Z)