Effects Zulresso on Postpartum Psychosis

Study Overview
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Brief Summary
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This is an open-label, proof of concept trial to investigate the efficacy, safety and tolerability of Zulresso (brexanolone) administered to adult female subjects diagnosed with postpartum psychosis. This study will provide critical pilot data to determine whether there is similar treatment efficacy among patients with postpartum psychosis as observed to date in patients with postpartum depression.

Detailed Description
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This is a single site, open label study design to evaluate the efficacy, safety and tolerability of Zulresso in female subjects diagnosed with postpartum psychosis. Participants will be consented, and if possible, participation will be discussed with available family members. Participants will take a consent questionnaire prior to consenting to ensure the voluntary nature and understanding of study procedures. Participants will undergo a screening visit including diagnostic interviews, clinical laboratory assessments and an EKG to determine eligibility. If eligible, participants will be admitted in-patient to UNC Hospitals and administered a continuous 60-hour infusion of Zulresso using the approved FDA REMS protocol for postpartum depression. A target dose of 90 μg/kg/hour will be administered over a period of 2.5 days following a strict tapering schedule. Monitoring will occur for an additional 12 hours after the infusion. The subject will participate in 6 follow up visits at day 7 post-infusion, day 14, day 21, day 30, day 60 and day 90.

Official Title
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Open Label Study of the Efficacy, Safety and Tolerability of Zulresso in the Treatment of Adult Women With Postpartum Psychosis

Conditions
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Postpartum Psychosis

Intervention / Treatment
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* Drug: Brexanolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participating subjects sign an informed consent form; Age 18-45 years old; Onset of affective psychosis or mania symptoms in the 3rd trimester, within 4 weeks of delivery, or within 4 weeks of weaning; Clinician diagnosis of affective psychosis or mania; ≤12 months postpartum at screening Exclusion Criteria: Positive pregnancy test at screening or day 1; Recent pregnancy did not result in a live birth; Subject is in renal failure; Subject is in hepatic failure; Subject is anemic (hemoglobin ≤10 g/dL); Untreated or inadequately treated hypothyroidism or hyperthyroidism; History of schizophrenia, and/or schizoaffective disorder; Current/active alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label - Active Drug<br>Brexanolone (zulresso) infusion arm. All patients enrolled will receive active treatment with brexanolone. | Drug: Brexanolone<br>* Brexanolone injection is an Federal Drug Administration (FDA)-approved drug to treat postpartum depression. It is administered via continuous intravenous infusion over a 60-hour time period.<br>* Other names: Zulresso;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale (PANSS) score | The PANSS is a standardized, clinical interview that rates the presence and severity of psychosis. The PANSS yields a total average symptom score, based on 30 items rated from one to seven (range=30-210). Higher scores indicate more severe symptoms. | Baseline to post-treatment day 7 | 
| Change in Young Mania Rating Scale (YMRS) score | The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. The items are selected based upon the core symptoms of mania. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe symptoms. | Baseline to post-treatment day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Rating Scale for Depression (HAM-D) | The 17-item HAM-D will be used to rate the severity of depression in subjects who are already diagnosed as depressed. The HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D maximum score is 52 for the 17 items with a higher score indicating more severe symptoms. | Baseline to post-treatment day 7 | 
| Change in Edinburgh Postnatal Depression Scale (EPDS) | The EPDS is a 10-item subject-rated depressive symptom severity scale specific to the perinatal period. The EPDS maximum score is 30 with higher scores indicating more severe symptoms. | Baseline to post-treatment day 7 | 
| Change in Clinical Global Impression Scale (CGI) | The CGI is a validated scale to allow clinicians to measure a subject's change in illness severity from baseline. The CGI scale consists of three items. Only the first two items (CGI-S and CGI-I) will be used in this study. The CGI-S uses a seven-point Likert scale to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis. The CGI-I employs a seven-point Likert scale to measure the overall improvement in the subject's condition post-treatment. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-I scores range from 1 (very much improved) through to 7 (very much worse). | Baseline to post-treatment day 7 |