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).
Drug: PH94B
Intranasal administration of 100 microliters to each nostril 4 times a day
Other Name: Aloradine
Drug: Placebo
Intranasal administration of 100 microliters to each nostril 4 times a day.
Inclusion Criteria:
1. Written informed consent provided prior to conducting any study-specific assessment.
2. Male and female adults, 18 through 65 years of age, inclusive.
3. Current diagnosis of AjDA as defined in the Diagnostic and Statistical Manual of
Mental Disorders, 5th Edition.
4. Clinician-rated Hamilton Anxiety Scale (HAM-A) score ≥20 at Screening (Visit 1) and no
greater than 15% decrease at Baseline (Visit 2).
5. Clinician-rated Hamilton Depression Scale (HAM-D) total score <18 at Screening (Visit
1) and Baseline (Visit 2).
6. Clinical Global Impression - Severity Scale (CGI-S) score ≥4 at both Screening (Visit
1) and Baseline (Visit 2)
7. 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 investigational product (IP) administration. Effective methods of
contraception include: condoms with spermicide, diaphragm with spermicide, hormonal
contraceptive agents (oral, transdermal, or injectable), or implantable contraceptive
devices.
8. Males whose sexual partners are women of childbearing potential must commit to the
consistent and correct use of an effective method of birth control throughout the
study.
9. Negative COVID-19 test either in the presence of COVID-19 symptoms or after exposure
to someone with a positive COVID-19 test.
Exclusion Criteria:
1. Any history of schizophrenia or schizoaffective disorder.
2. Any other current Axis I disorder, including, but not limited to, major depressive
disorder, bipolar disorder, post-traumatic stress disorder, obsessive-compulsive
disorder, premenstrual dysphoric disorder, and generalized anxiety disorder, which is
in poor control and the primary focus of treatment.
3. A diagnosis of social anxiety disorder with a score >60 on the Liebowitz Social
Anxiety Scale.
4. Subjects who meet criteria for moderate or severe alcohol or substance use disorder
within the 1 year prior to Study entry.
5. 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.
6. 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.
7. 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. The Investigator may
allow concomitant use of over-the-counter nasal decongenstants as needed, since there
is no apparent drug interaction between these and PH94B.
8. Concomitant use of any anxiolytics, such as benzodiazepines or buspirone, during the
Study and within 30 days of Baseline (Visit 2).
9. Concomitant use of any over-the-counter, prescription product, or herbal preparation
for treatment of the symptoms of anxiety during the Study and within 30 days before
Study entry. Selective serotonin reuptake inhibitors, serotonin-norepinephrine
reuptake inhibitors, or other approved antidepressants are permitted as long as the
dose has been stable for 30 days prior to Baseline (Visit 2).
10. Women who have a positive urine or serum pregnancy test at either Screening or
Baseline visit or are currently breast feeding.
11. Subjects with clinically significant abnormalities in hematology, blood chemistry,
urinalysis, electrocardiogram, or physical examination identified at the Screening
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.
12. Subjects with a positive urine drug screen at either the Screening visit or Baseline
visit (not including tetrahydrocannabinol).
13. 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.
14. Use of a concomitant medication that, in the clinical judgement 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.
VistaGen Clinical Site
Watertown, Massachusetts, United States
VistaGen Clinical Site
New York, New York, United States
Matt Turzilli
212-595-5012
mturzilli@medicalresearchnetwork.com