A Clinical Trial of Oral Ganaxolone in Women With Postpartum Depression

Study Overview
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Brief Summary
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A clinical study to evaluate safety, tolerability and efficacy of oral administration of ganaxolone in women with postpartum depression

Official Title
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A Phase 2, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Oral Administration of Ganaxolone in Women With Postpartum Depression

Conditions
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Depressive Disorder, Depression, Depression, Postpartum, Behavioral Symptoms, Mood Disorders, Mental Disorder, Pregnancy Complications, Postpartum Blues, PPD, Postpartum Disorder

Intervention / Treatment
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* Drug: Ganaxolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Experiencing a major depressive episode, which started between the start of the third trimester and 4 weeks following delivery. The major depressive episode must be diagnosed according to Mini International Neuropsychiatric Interview (MINI) 7.0 interview Given birth in the last 6 months HAMD17 score of ≥ 20 at screening but < 26 Must agree to stop breastfeeding from start of study treatment or must agree to temporarily cease giving breast milk to her infant(s) Exclusion Criteria: Current history of any psychotic illness, including major depressive episode with psychotic features History of suicide attempt within the past 3 years History of bipolar I disorder History of seizure discorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganaxolone<br>Oral | Drug: Ganaxolone<br>* Oral<br>|
| Placebo Comparator: Placebo<br>Oral | Drug: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Through Treatment | The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. | Baseline (Day 1) and through Day 10 for 2 week treatment group and Day 29 for 4 week treatment groups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment | The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. | Baseline (Day 1) and Through Day 38 for 2 week treatment group and Day 71 and 119 for 4 week treatment groups | 
| Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17) | HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with response to HAMD-17 has been presented. | Day 2 (all treatment groups), Day 7 (TID & QHS), Day 8/10 (all treatment groups), Day 15/17 (all treatment groups), Day 22 and 29 (QHS, 1125mg), Day 36/38 (all treatment groups), Day 57/59 (QHS, 1125mg), Day 71 (1125mg), Day 89 (QHS), Day 119 (QHS) | 
| Number of Participants With Hamilton Depression Rating Scale 17-item Remission | Remission was defined as an observed total score of 0 to 7. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with HAMD-17 remission has been presented. | Day 8/10 (all treatment arms), Day 15/17 (all treatment arms), Day 22 and 29 (QHS & 1125mg), Day 36/38 (all treatment arms), Day 57/59 (QHS & 1125mg), Day 71 (1125mg), Day 89 & 119 (QHS) | 
| Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score | The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. | Baseline (Day 1) through Day 119 | 
| Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version | The Spielberger State-Trait Anxiety Inventory was a 6-item questionnaire designed and validated. It is a reliable and sensitive measure of anxiety. The 6-item version has been shown to have acceptable reliability, producing similar scores as the full 20-item inventory for those with normal and raised levels of anxiety. Participants are prompted to respond to indicate how [the participant] feel right now, at this moment, followed by a list of common experiences like I feel calm, I am tense, I feel upset, I am relaxed I feel content and I am worried. Responses range from Not at all (1) to Very much (4), with overall scores ranging from 20-80, where higher scores reflected higher states of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. | Baseline (Day 1) through Day 119 | 
| Number of Participants With Clinical Global Impression-Improvement | The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Only those participants with CGI- improvement have been presented. | Baseline through Day 119 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postpartum Care, Postpartum Depression