Social Anxiety Disorder
Conditions
Brief summary
This study evaluates the safety and tolerability of PH94B with repeated dosing over a period of up to 12 months. Participating subjects will use PH94B up to 4 times a day when they encounter anxiety-provoking situations in daily life. Safety and tolerability of PH94B (≤ 4 doses per day up to 12 months) will be assessed and summarized during monthly visits from baseline (Visit 2) to end of treatment (Visit 14) in AEs, laboratory values, 12-lead ECGs, physical examinations, and vital sign assessments following exposure to PH94B.
Interventions
DRUGPH94B
Nasal spray
Sponsors
VistaGen Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Most but not all patients will enter the study following completion of Palisade-1 (NCT047548020) and Palisade-2 (NCT05011396). Inclusion Criteria: 1. Male and female adults, 18 through 65 years of age, inclusive. 2. Women of childbearing 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) (for subjects who attend 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. 3. Current diagnosis of social anxiety disorder 4. Clinician-rated HAM-D17 total score \< 18 at study entry 5. LSAS score 50 or greater
Exclusion criteria
1. Any history of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, psychosis, anorexia or bulimia, autism-spectrum 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. 4. Clinically significant nasal pathology or history of significant nasal trauma, nasal surgery, total 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. Subjects using the following psychotropic medications: anticonvulsants, mood stabilizers, antipsychotic medications, gabapentin, pregabalin, opioids, naltrexone, esketamine, and ketamine at enrollment. Subjects using lower doses of atypical antipsychotics at Screening may be eligible after discussion with the Medical Monitor (e.g., quetiapine \< 100 mg). In general, subjects using antidepressants or buspirone can continue to receive these provided that they have been taking them for a minimum of 2 months, and have been on a stable dose for a minimum of 1 month. 7. Use of anxiolytics, such as benzodiazepines or unapproved treatments such as beta blockers, within 30 days before study entry; concomitant use is prohibited during the study. Subjects who have been taking benzodiazepines daily for 1 month or longer at the time of Visit 1 are not eligible to participate. 8. Use of any over-the-counter product, prescription product, or herbal preparation for treatment of the symptoms of anxiety or social anxiety within 30 days before study entry; concomitant use is prohibited during the study. 9. Subjects with clinically significant abnormalities in hematology, blood chemistry, urinalysis, 12-lead ECG, 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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 12 months | Subjects with at least one Serious Adverse Event (SAE) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | V 2 (Baseline), V 3 (Month 1), V 4 (Month 2), V 5 (Month3), V 6 (Month 4), V 7 (Month 5), V 8 (Month 6), V 9 (Month 7), V 10 (Month 8), V11 (Month 9) | The LSAS is a clinician-rated scale that has been shown to be sensitive to treatment-related change in social anxiety symptoms. The scale consists of 24 items. Each item is given 2 ratings: fear or anxiety on scale of 0 to 3 (with 0 = none and 3 = severe) and avoidance on a scale of 0 to 3 (with 0 = never and 3 = usually), with a total maximum overall score of 144. The sum of the 24 fear or anxiety items and the sum of the 24 avoidance items are combined for a total LSAS score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PH94B PH94B Nasal Spray - administration of 3.2 micrograms PH94B, as needed, up to four times per day. | 481 |
| Total | 481 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Lost to Follow-up | 35 |
| Overall Study | Other | 8 |
| Overall Study | Positive Drug Screen | 4 |
| Overall Study | Pregnancy | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Study terminated by sponsor | 349 |
| Overall Study | Withdrawal by Subject | 60 |
Baseline characteristics
| Characteristic | PH94B |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 481 Participants |
| Age, Continuous | 36.4 years STANDARD_DEVIATION 12.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants |
| Race (NIH/OMB) Asian | 41 Participants |
| Race (NIH/OMB) Black or African American | 87 Participants |
| Race (NIH/OMB) More than one race | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 318 Participants |
| Region of Enrollment United States | 481 participants |
| Sex: Female, Male Female | 300 Participants |
| Sex: Female, Male Male | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 481 |
| other Total, other adverse events | 137 / 481 |
| serious Total, serious adverse events | 6 / 481 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Subjects with at least one Serious Adverse Event (SAE)
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least 1 TEAE leading to study discontinuation | 14 Participants |
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least 1 SAE | 6 Participants |
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least one TEAE | 273 Participants |
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least 1 Mild TEAE | 186 Participants |
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least 1 Moderate TEAE | 78 Participants |
| PH94B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Subjects with at least 1 Severe TEAE | 9 Participants |
Other Pre-specified
Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B
The LSAS is a clinician-rated scale that has been shown to be sensitive to treatment-related change in social anxiety symptoms. The scale consists of 24 items. Each item is given 2 ratings: fear or anxiety on scale of 0 to 3 (with 0 = none and 3 = severe) and avoidance on a scale of 0 to 3 (with 0 = never and 3 = usually), with a total maximum overall score of 144. The sum of the 24 fear or anxiety items and the sum of the 24 avoidance items are combined for a total LSAS score.
Time frame: V 2 (Baseline), V 3 (Month 1), V 4 (Month 2), V 5 (Month3), V 6 (Month 4), V 7 (Month 5), V 8 (Month 6), V 9 (Month 7), V 10 (Month 8), V11 (Month 9)
Population: The number analyzed differs from overall number analyze as PH94B-CL030 was terminated early by the sponsor
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 5 (Month 3) | 67.6 score on a scale | Standard Deviation 25.58 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 2 (Baseline) | 93.4 score on a scale | Standard Deviation 18.79 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 3 (Month 1) | 76.6 score on a scale | Standard Deviation 24.63 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 4 (Month 2) | 73.0 score on a scale | Standard Deviation 25.09 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 6 (Month 4) | 66.0 score on a scale | Standard Deviation 24.85 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 7 (Month 5) | 64.8 score on a scale | Standard Deviation 24.91 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 8 (Month 6) | 65.2 score on a scale | Standard Deviation 23.7 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 9 (Month 7) | 61.1 score on a scale | Standard Deviation 26.44 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 10 (Month 8) | 54.0 score on a scale | Standard Deviation 21.52 |
| PH94B | Change in Total Liebowitz Social Anxiety Scale (LSAS) Scores Over Time With Use of PH94B | Visit 11 (Month 9) | 54.4 score on a scale | Standard Deviation 7.76 |