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Articles   |    
Effect of an Acute Intranasal Aerosol Dose of PH94B on Social and Performance Anxiety in Women With Social Anxiety Disorder
Michael R. Liebowitz, M.D.; Ester Salman; Humberto Nicolini, M.D.; Norman Rosenthal, M.D.; Rita Hanover, Ph.D.; Louis Monti, M.D., Ph.D.
Am J Psychiatry 2014;171:675-682. doi:10.1176/appi.ajp.2014.12101342
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Dr. Liebowitz has had clinical trial contracts with Abbott, Allergan, AstraZeneca, Avera, Cephalon, Cerecor, Endo, Forest, GlaxoSmithKline, Gruenthal, Horizon, Indevus, Jazz, Johnson & Johnson, Lilly, Lundbeck, MAP, MSI, Naurex, Novartis, Ortho-McNeil, Otsuka, Pfizer, PGX Health, Purdue Pharma, Sepracor, Shionogi, Takeda, Teva, Tikvah, and Wyeth and has received investigator-initiated trial support from Forest and Pfizer; he has served as a consultant, speaker, or presenter for AstraZeneca, Avera, Concert, Eisai, Eli Lilly, Forest, Johnson & Johnson, Otsuka, Pfizer, Pherin, Sunovion, Takeda, Tikvah, and Wyeth; he has had equity ownership in Pherin Pharmaceuticals (stock options), in the Liebowitz Social Anxiety Scale, and in ChiMatrix and has received licensing fees for software for the Liebowitz Social Anxiety Scale from Avera, Eli Lilly, Endo, GlaxoSmithKline, Indevus, Pfizer, Tikvah, and Servier. Ms. Salman has stock options in Pherin Pharmaceuticals. Dr. Nicolini has received research support from Pherin and Servier and has served as a consultant or on advisory boards for MSD, Sanofi, and Servier. Dr. Rosenthal reports no financial relationships with commercial interests. Dr. Hanover has served as a consultant to, and has stock options in, Pherin Pharmaceuticals. Dr. Monti has equity ownership in Pherin Pharmaceuticals (shares and stock options).

Supported by Pherin Pharmaceuticals, Inc., Los Altos, Calif.

Clinicaltrials.gov identifier: NCT01217788.

From the Medical Research Network, New York, and the Department of Psychiatry, Columbia University, New York; ChiMatrix, Scarsdale, N.Y.; Carracci Medical Group, Mexico City; the Department of Psychiatry, Georgetown University Medical School, Washington, D.C.; Capital Clinical Research Associates, Rockville, Md.; Westchester Medical Center, Valhalla, N.Y.; and Pherin Pharmaceuticals, Los Altos, Calif.

Presented in part at the 51st annual meeting of the NIMH New Clinical Drug Evaluation Unit, Boca Raton, Fla., June 13–16, 2011.

Address correspondence to Dr. Liebowitz (mrliebowitz@yahoo.com).

Copyright © 2014 by the American Psychiatric Association

Received October 22, 2012; Revised August 16, 2013; December 16, 2013; Accepted February 10, 2014.

Abstract

Objective  Although social anxiety disorder is a common and sometimes disabling condition, there are no approved treatments that can be used on an as-needed basis. The authors examined the acute use of PH94B, an intranasally administered neurosteroidal aerosol, for the acute management of the symptoms of social anxiety disorder.

Method  The authors conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled, single-dose study of PH94B. Ninety-one women 19–60 years of age with generalized social anxiety disorder received placebo intranasal spray (single-blind) 15 minutes before laboratory-simulated public speaking and social interaction challenges. Patients who experienced significant distress during at least one challenge returned 1 week later to receive either intranasal PH94B or placebo aerosol spray (double-blind) before repeat challenges.

Results  Patients who received PH94B during the second set of challenges had a significantly greater decrease in mean Subjective Units of Distress scores during the public speaking and social interaction challenges compared with the first set of challenges, than did patients who received placebo for both sets of challenges. A significantly greater proportion of the PH94B group were much or very much improved from the first to the second sets of challenges compared with the placebo group (75% and 37%, respectively). The side effects of PH94B were benign.

Conclusions  PH94B may be a novel, effective, and well-tolerated acute treatment for performance and social anxiety in women with social anxiety disorder.

Abstract Teaser
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FIGURE 1. CONSORT Diagram for a Phase 2 Clinical Study of Acute Intranasal Aerosol PH94B in Women With Social Anxiety Disorder

a The patient presented with social anxiety disorder and met study criteria, but because she appeared very outgoing and social during the study, the investigators believed that she had been misdiagnosed.

b At audit, the investigators could not verify whether the patient had received PH94B or placebo.

FIGURE 2. Public Speaking Challenge, Minute-by-Minute Subjective Units of Distress Scores for Women With Social Anxiety Disorder Receiving Intranasal Aerosol PH94B (N=45) or Placebo (N=46)a

a At visit 2, both groups received placebo. R=resting.

FIGURE 3. Social Interaction Challenge, Minute-by-Minute Subjective Units of Distress Scores for Women With Social Anxiety Disorder Receiving Intranasal Aerosol PH94B (N=45) or Placebo (N=46)a

a At visit 2, both groups received placebo. R=resting.

Anchor for Jump
TABLE 1.Subjective Units of Distress Scores for Women With Social Anxiety Disorder Receiving Intranasal Aerosol PH94B or Placebo Before and During Public Speaking and Social Interaction Challenges
Table Footer Note

a At visit 2, both groups received placebo.

Anchor for Jump
TABLE 2.Adverse Events Reported During the Study by Women With Social Anxiety Disorder Receiving Intranasal Aerosol PH94B or Placeboa
Table Footer Note

a No significant differences between groups on any safety outcome.

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The effect of intranasal PH94B lasts approximately how long?
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