Efficacy, Safety, and Tolerability of PH94B in Adjustment Disorder With Anxiety: Design of an Exploratory Phase 2A Clinical Trial
Annals of Clinical Psychiatry
; 34(3):19-20, 2022.
Article
in English
| EMBASE | ID: covidwho-2030704
ABSTRACT
BACKGROUND:
Adjustment disorders are now primary diagnoses in the trauma and stressrelated disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Adjustment disorder with anxiety (AjDA) is the development of emotional or behavioral symptoms considered excessive in response to stressful events, significantly impairing a person's ability to function in social, occupational, and/ or other situations. Traumatic experiences related to the COVID-19 pandemic may have increased rates of adjustment disorders, especially among those whose life routines were disrupted by pandemic-associated stress and anxiety. PH94B (3b-hydroxy-androsta-4,16-dien-ol) has shown rapid-onset efficacy in the treatment of social anxiety disorder (Liebowitz et al. Am J Psychiatry. 2014). PH94B is a neuroactive steroid administered as a nasal spray that engages olfactory chemosensory neurons, activating subsets of olfactory bulb neurons that project directly to the limbic amygdala regulating fear and anxiety circuits.OBJECTIVE:
To assess the efficacy, safety, and tolerability of PH94B in adults with AjDA.METHODS:
This is an exploratory, phase 2A, randomized, double-blind, 4-week, placebo-controlled, 2-arm study in adults with AjDA. The primary outcome is change from baseline to week 4 in the Hamilton Anxiety Rating Scale (HAM-A) total score after intranasal administration of PH49B 4 times daily vs placebo. Patients with a DSM-5 diagnosis of AjDA confirmed by the Mini-International Neuropsychiatric Interview (MINI) with Adjustment Disorders Module and a clinician-rated HAM-A score of ≥20 at screening (Visit 1), with ≤15% decrease at baseline (Visit 2, randomization) are eligible for inclusion. Secondary outcomes include change from baseline to week 4 in the Adjustment Disorder New Module Scale (ADNM), the International Adjustment Disorder Questionnaire (IADQ), the Clinical Global Impression of Improvement (CGI-I), and the Patient Global Impression of Change (PGI-C). Change from baseline in the Hamilton Depression Rating Scale (HAM-D) was exploratory.RESULTS:
A total of 40 patients will be randomized (11 drug to placebo). The study design features the use of the ADNM and IADQ, newly developed according to ICD-11 criteria for evaluation of AjDA. While both are validated, neither has been tested in placebo-controlled clinical trials. Both scales begin with a list of stressors (18 for ADNM and 9 for IADQ);a yes answer to any 1 stressor triggers a series of questions about the frequency and duration of a patient's reaction to the stressor (ADNM) or quantifies symptoms in response to the stressor (IADQ).CONCLUSIONS:
Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. Anxiety and impaired functioning are increasing, particularly in response to the COVID-19 pandemic, and no pharmacologic treatment is currently approved by the FDA for AjDA. PH94B, an investigational pherine nasal spray, is also being studied for treatment of other anxiety-related disorders.
fasedienol; nose spray; placebo; adjustment disorder; adult; amygdala; anxiety; anxiety disorder; clinical article; Clinical Global Impression scale; clinical trial; comparative effectiveness; conference abstract; controlled study; coronavirus disease 2019; depression; disability; double blind procedure; drug safety; drug therapy; drug tolerability; DSM-5; exploratory research; fear; female; Hamilton Anxiety Scale; Hamilton Depression Rating Scale; human; ICD-11; intranasal drug administration; male; mental disease; mini international neuropsychiatric interview; nerve cell; olfactory bulb; outcome assessment; pandemic; pH; phase 2 clinical trial; psychiatry; questionnaire; randomization; randomized controlled trial; social phobia
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Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Annals of Clinical Psychiatry
Year:
2022
Document Type:
Article
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