Feasibility Study of PH94B Nasal Spray for Acute Treatment of Social Anxiety Disorder (SAD)

The study is a randomized, double-blind, placebo-controlled, 2-way crossover trial of the efficacy and safety of PH94B in the treatment of subjects diagnosed with Social Anxiety Disorder as defined by the Diagnostic and Statistical Manual IV and confirmed by the MINI (5.0.0). The study is intended to serve as a feasibility trial of a multi-center phase 3 study protocol of similar design.

The primary objective of this study is to evaluate design features for a larger Phase 3 study that will evaluate the safety and efficacy of PH94B for the acute management of symptoms in subjects with Social Anxiety Disorder. Careful review of diary entries and measurement of study medication compliance each week will be used to determine the feasibility of using the study medication on an "as needed" basis for anxiety-provoking social events. Specifically, the frequency of use, variability of SUDS ratings, effect size of differences in average peak SUDS ratings during treatment with PH94B and placebo, and general reliability of the diary recording method will be evaluated and used to refine inclusion and exclusion criteria as well as provide guidance for designing a larger multi-site study.

The study will last a total of 6-8 weeks. The randomized double-blind treatment period will last a total of four weeks for all subjects.

Inclusion criteria

• Written informed consent provided prior to conducting any study-specific assessment.
• Male and female adults, 18 through 65 years of age, inclusive.
• Current diagnosis of Social Anxiety Disorder as defined in the DSM IV of Mental Disorders, which is not secondary to another pre-existing psychiatric condition or to a medical condition.
• Confirmation of diagnosis of Social Anxiety Disorder according to the MINI, 5.0.0
• Clinician-rated Liebowitz Social Anxiety Scale total score ≥60 at both Screening and Baseline visits.
• Clinician-rated HAM-D17 total score <18 at both Screening and Baseline visits.
• CGI-Severity score ≥4 at both Screening and Baseline visits.
• Subject must have:

• experienced and documented a minimum total of six social interaction or performance events during the two week Screening Period prior to the Baseline Visit, and
• for at least three of these events, must have achieved a peak score of ≥60 on the Subjective Units of Distress Scales (SUDS), as rated in the Patient Diary.
• 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 have a negative urine pregnancy test result prior to study medication administration.

Exclusion criteria

• History of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, psychosis, eating disorder, 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 (GAD) are eligible for the study provided that GAD is not the primary diagnosis.
• Subjects who meet criteria for substance abuse within the year prior to entry.
• Clinically significant nasal pathology or history of significant nasal trauma, nasal surgery, or nasal-septal 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 during the previous six months, whereby a treatment trial is defined as a period of at least six (6) weeks (or longer as documented in package insert for a particular drug) during which the patient received an adequate dosage (defined as the treatment dose indicated in the package insert to obtain efficacy for that particular drug) of the medication.
• Use of any psychotropic medication within 30 days prior to study entry (other than eszopiclone, ramelteon, zaleplon, or zolpidem for insomnia as described in Section 3.3).
• Concomitant use of non-study anxiolytics such as benzodiazepines or beta blockers during the study and within 30 days prior to study entry.
• Concomitant use of any over-the-counter, prescription product, or herbal preparation for treatment of the symptoms of social anxiety during the study and within 30 days prior to study entry.
• Prior exposure to PH94B.
• Improvement of more than 20% in the LSAS score at Baseline relative to Screening.
• Women who have a positive urine human chorionic gonadotropin pregnancy test prior to study medication administration.
• Subjects with clinically significant abnormalities in hematology, blood chemistry, urinalysis, ECG, or physical examination identified at the Screening or Baseline visit.
• Subjects with a positive urine drug screen at either the Screening or Baseline visit.
• Presence of any clinical condition or disease, or use of a concomitant medication, that in the clinical judgment of the Investigator could place the patient at undue risk, interfere with study participation, or confound the results of the study.